<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02222246</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00054047</org_study_id>
    <secondary_id>R34 RHL121224A</secondary_id>
    <nct_id>NCT02222246</nct_id>
  </id_info>
  <brief_title>Comparing Acute Pain Management Protocols for Patients With Sickle Cell Disease</brief_title>
  <official_title>Comparing Acute Pain Management Protocols for Patients With Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Cincinnati</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mount Sinai Hospital, New York</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this pilot study is to improve emergency department (ED) pain management for&#xD;
      adults with sickle cell disease. Sickle cell disease (SCD) is the most common genetic&#xD;
      disorder in the United States, and occurs primarily among African Americans. Management of&#xD;
      painful episodes associated with SCD, referred to as vaso-occlusive crises (VOC), is the most&#xD;
      common reason for SCD patients to visit the ED. Currently, there is no standard approach to&#xD;
      managing VOC pain in the ED that is widely accepted and used, and pain management for&#xD;
      vaso-occlusive crisis in persons with SCD is very different between providers and not based&#xD;
      on research. Many times, patients who come to the ED with sickle cell pain feel that they do&#xD;
      not receive adequate pain control. If EDs could provide efficient, effective, safe,&#xD;
      patient-centered analgesic management, it may be possible to improve pain management for&#xD;
      adults with SCD experiencing a VOC. Guidelines for treating vaso-occlusive crises caused by&#xD;
      sickle cell disease will soon be published by the National Heart, Lung and Blood Institute of&#xD;
      the National Institutes of Health. These guidelines recommend patient-specific pain treatment&#xD;
      protocols or a standardized pain management protocol for SCD when a patient does not already&#xD;
      have a pain treatment protocol designed for them. The purpose of this pilot study is to&#xD;
      compare these two ways to treat vaso-occlusive pain in the ED for adults with sickle cell&#xD;
      disease, and to determine if a large randomized controlled trial is feasible and required.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In August 2012 the National Heart, Lung, and Blood Institute (NHBLI) released for public&#xD;
      comment their &quot;Management of Sickle Cell Disease&quot; evidence-based recommendations that were&#xD;
      developed with consensus panel expertise. Because of a lack of empirical data, most of the&#xD;
      recommendations specific to vaso-occlusive crises (VOC) were based on consensus panel&#xD;
      expertise. Recommendations included the use of a patient-specific protocol (specific agents&#xD;
      and doses for an individual patient). While many attempts have been made to implement&#xD;
      patient-specific analgesic protocols for use in emergency departments (EDs), anecdotally,&#xD;
      these have been difficult to implement and maintain over time; a practical approach to&#xD;
      development, implementation, and dissemination has not been determined. As patient-specific&#xD;
      protocols are not available in most EDs, the guidelines go on to recommend a SCD specific&#xD;
      standard analgesic protocol. Both of these recommended protocols provide more aggressive VOC&#xD;
      pain management than a typical generic ED pain protocol. However, there is an urgent need to&#xD;
      rigorously test the NHLBI recommendations and compare the two approaches for managing VOC in&#xD;
      the ED. A large randomized clinical trial (RCT) is essential to test these protocols.&#xD;
&#xD;
      This pilot project will compare these two different, evidence-based, protocols which include&#xD;
      opioid pain medicines routinely used as standard of care to treat VOC pain in the ED for&#xD;
      individuals with SCD, and collect the data necessary to determine if a large RCT is feasible&#xD;
      and required. This study is novel in that it will design an approach to develop and implement&#xD;
      patient-specific and standard analgesic VOC protocols for use in the ED, will develop a&#xD;
      bundle of information technology and education interventions to enhance protocol adoption for&#xD;
      the pilot RCT, and also be the first RCT conducted in an ED setting to compare two different&#xD;
      ED pain management protocols for SCD patients who experience a VOC.&#xD;
&#xD;
      The study consists of 3 aims:&#xD;
&#xD;
        1. Develop and implement patient specific VOC protocols for patients randomized to this&#xD;
           arm,&#xD;
&#xD;
        2. Conduct a pilot RCT to determine the necessary sample size needed for a large RCT to&#xD;
           compare the difference in reduction in pain score from ED arrival to discharge,&#xD;
           hospitalization, clinical and safety outcomes, between subjects assigned randomly to&#xD;
           either a standard SCD analgesic protocol or to a patient-specific analgesic protocol,&#xD;
&#xD;
        3. Measure feasibility of methods and acceptability of and fidelity to protocols by&#xD;
           evaluating optimal recruitment and retention strategies, and assessing ED providers&#xD;
           perceptions of facilitators and barriers to protocol use and protocol adherence.&#xD;
&#xD;
      The soon to be published NHBLI guidelines for managing SCD will be used as the standard&#xD;
      protocol with the modification of basing the initial dose of pain medicine on patient weight.&#xD;
      The standard protocol will recommend re-assessment, and re-dosing with possible dose&#xD;
      escalation, every 20-30 minutes. Repeat doses for patients randomized to the weight-based&#xD;
      protocol, when necessary, will be maintained or provided at 1 dose level increase (no more&#xD;
      than 25%) above the initial dose. For patients randomized to the patient -specific protocol,&#xD;
      the SCD provider has experience with the individual patient and is best qualified to make&#xD;
      dosing and frequency recommendations based upon doses required during past ED and hospital&#xD;
      visits for treatment of VOC, and on daily opioid use if applicable. There is no set maximum&#xD;
      dose for patients randomized to the patient-specific protocols.&#xD;
&#xD;
      Both the patient-specific and standard protocols will be available in the ED via a patient's&#xD;
      electronic medical record. Upon ED arrival, providers will retrieve the patient's study&#xD;
      protocol (patient-specific, or standard) which will include the starting agents, and doses,&#xD;
      the subsequent analgesic recommendations, and order medications according to the&#xD;
      pre-determined protocol.&#xD;
&#xD;
      The study will be conducted at the emergency departments of the University of Cincinnati&#xD;
      Medical Center and the Mt. Sinai Hospital in New York. Patients will be enrolled in the study&#xD;
      for up to 12-months, but may contribute no more that five different ED visits for VOC pain&#xD;
      control during enrollment to allow for a larger number of different patients.&#xD;
&#xD;
      Study outcomes will be compared between ED visits of patients randomized to a&#xD;
      patient-specific vs. a standard SCD protocol. The primary outcome will be the difference in&#xD;
      pain score from ED arrival to discharge, up to 6 hours, as measured using a visual analogue&#xD;
      scale. The trajectories of average pain scores from immediately prior to administration of&#xD;
      1st analgesic dose to discharge by 30 minute increments for each treatment group will also be&#xD;
      calculated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 15, 2015</start_date>
  <completion_date type="Actual">June 30, 2016</completion_date>
  <primary_completion_date type="Actual">May 31, 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in Pain Score as Measured by a Visual Analogue Scale (VAS)</measure>
    <time_frame>Arrival in ED to discharge from the ED, up to 6 hours</time_frame>
    <description>Each ED study visit was the unit of analysis for the statistical methods addressing the primary outcome. The primary outcome was change in pain score from arrival to discharge. Pain severity was assessed at arrival and discharge from ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating &quot;no pain&quot; and 100 indicating &quot;pain as bad as it could be&quot; or &quot;worst imaginable pain&quot;.Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED. Thus, the difference in pain scores were calculated as the arrival minus discharge VAS scores, with higher positive pain difference or change scores indicating greater pain reduction.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Pain Visual Analogue Scale (VAS) Scores Over Time</measure>
    <time_frame>Every 30 minutes from arrival in ED to discharge from the ED, up to 6 hours</time_frame>
    <description>Pain severity was assessed at arrival and every 30 minutes until discharge from the ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating &quot;no pain&quot; and 100 indicating &quot;pain as bad as it could be&quot; or &quot;worst imaginable pain&quot;. Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED.&#xD;
A hierarchical random coefficients regression model for repeated measurements (type of mixed hierarchical mixed-effect model) was conducted on the pain scores collected at six time points (arrival, post-placement 30-min, 60-min, 90-min,120-min, discharge) to evaluate the trajectory of change in pain. Discharge occurred at 120 minutes or later during each visit, with the exception of one discharge at 54 minutes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Nausea During Emergency Department Visits</measure>
    <time_frame>From placement in Emergency Department (ED) treatment room to discharge from the ED, up to 6 hours</time_frame>
    <description>Nausea at any point from placement until discharge, based on nausea data collected every 30 minutes during that time period. Thus, a nausea variable was derived in which 0=no and 1=yes that nausea was reported by the patient at least once during the placement to discharge time interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Vomiting During Emergency Department Visits</measure>
    <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
    <description>Vomiting at any point from placement until discharge, based on vomiting data collected every 30 minutes during that time period. Thus, a vomiting variable was derived in which 0=no and 1=yes that vomiting was reported by the patient at least once during the placement to discharge time interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of a Decrease in Systolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit</measure>
    <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
    <description>Decrease in systolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A systolic variable was derived in which 0=no and 1=yes that a &gt;= 20% decrease of baseline systolic blood pressure was reported by the patient at least once during the placement to discharge time interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of a Decrease in Diastolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit</measure>
    <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
    <description>Decrease in diastolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A diastolic variable was derived in which 0=no and 1=yes that a &gt; 20% decrease of baseline diastolic blood pressure was reported by the patient at least once during the placement to discharge time interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Oxygen Desaturation (&lt; 95%) (YES) During Emergency Department Visit</measure>
    <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
    <description>Saturation of peripheral capillary oxygen &lt; 95% (SPO2 &lt; 95%) at any point from placement until discharge, based on SPO2 data collected every 30 minutes during that time period. Thus, a SPO2 variable was derived in which 0=no and 1=yes that SPO2 &lt; 95% was reported by the patient at least once during the placement to discharge time interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Respiratory Distress (YES) During Emergency Department Visit</measure>
    <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
    <description>Respiratory distress at any point from placement until discharge, based on data collected every 30 minutes during that time period. Thus, a respiratory distress variable was derived in which 0=no and 1=yes that respiratory distress was reported by the patient at least once during the placement to discharge time interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Sedation During Emergency Department Visit</measure>
    <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
    <description>Severe-to moderate sedation at any point from placement until discharge, based on sedation data collected every 30 minutes during that time period. Thus, a sedation variable was derived in which 0=no and 1=yes that moderate-severe sedation was reported by the patient at least once during the placement to discharge time interval. Sedations scoring was as follows: None was defined as &quot;awake and alert&quot;, Mild sedation was defined as &quot;responds to voice&quot;, Moderate sedation was defined as &quot;responds to touch, with or without voice&quot; and Severe sedation was defined as &quot;somnolent, difficult to arouse&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of the Need for Supplemental Oxygen During Emergency Department Visit</measure>
    <time_frame>Following the initiation of opioid therapy until discharge from the ED, up to 6 hours</time_frame>
    <description>Need for supplemental oxygen during the Emergency Department stay; this was determined at discharge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of the Administration of Naloxone During Emergency Department Visit</measure>
    <time_frame>Following the initiation of opioid therapy until discharge from the ED, up to 6 hours</time_frame>
    <description>Naloxone administered during the Emergency Department stay; this was determined at discharge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of the Need for Assistive Ventilation</measure>
    <time_frame>Following the initiation of opioid therapy until discharge from the ED, up to 6 hours</time_frame>
    <description>Intubation or other assistive ventilation techniques - including bag, valve, or mask was performed during the ED stay; this was determined at discharge.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">106</enrollment>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>Patient Specific dose of Morphine Sulfate or Hydromorphone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 5 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard dose of Morphine Sulfate or Hydromorphone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydromorphone (Standardized, weight-based dosing)</intervention_name>
    <description>Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
    <arm_group_label>Standard dose of Morphine Sulfate or Hydromorphone</arm_group_label>
    <other_name>Dilaudid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine Sulfate (Standardized, weight-based dosing)</intervention_name>
    <description>Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
    <arm_group_label>Standard dose of Morphine Sulfate or Hydromorphone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydromorphone (Patient Specific dosing)</intervention_name>
    <description>Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
    <arm_group_label>Patient Specific dose of Morphine Sulfate or Hydromorphone</arm_group_label>
    <other_name>Dilaudid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine Sulfate (Patient Specific dosing)</intervention_name>
    <description>Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
    <arm_group_label>Patient Specific dose of Morphine Sulfate or Hydromorphone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult SCD patients with genotypes SS, SC, SB+, or SB-&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with sickle cell trait&#xD;
&#xD;
          -  Allergic to both morphine sulfate and hydromorphone,&#xD;
&#xD;
          -  Patients who have an explicit care plan that states they cannot be admitted to the&#xD;
             hospital for pain control,&#xD;
&#xD;
          -  Non-English speaking,&#xD;
&#xD;
          -  Patients admitted for a medical complication,&#xD;
&#xD;
          -  Record of &gt;24 ED visits in the prior 12 months,&#xD;
&#xD;
          -  Children&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paula Tanabe, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University School of Nursing</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <results_first_submitted>May 12, 2017</results_first_submitted>
  <results_first_submitted_qc>July 31, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 4, 2017</results_first_posted>
  <last_update_submitted>July 31, 2017</last_update_submitted>
  <last_update_submitted_qc>July 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sickle Cell Disease</keyword>
  <keyword>Emergency Department</keyword>
  <keyword>Vaso-occlusive Crisis</keyword>
  <keyword>Pain Management</keyword>
  <keyword>Pilot Project</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
    <mesh_term>Acute Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Hydromorphone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>106 subject were enrolled and consented to participation during all future Emergency Department (ED) visits for vaso-occlusive crises (VOC), should they occur, over the study period. 53 subjects were randomized to each arm.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
          <description>A standardized analgesic protocol (based on recent National Heart, Lung, and Blood Institute (NHBLI) recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a Sickle Cell Disease (SCD) specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
        </group>
        <group group_id="P2">
          <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
          <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
                <participants group_id="P2" count="53"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>No Emergency Department Visits</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
          <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
        </group>
        <group group_id="B2">
          <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
          <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="26"/>
            <count group_id="B2" value="26"/>
            <count group_id="B3" value="52"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.0" lower_limit="23.0" upper_limit="33.0"/>
                    <measurement group_id="B2" value="28.5" lower_limit="23.0" upper_limit="32.0"/>
                    <measurement group_id="B3" value="27.0" lower_limit="23.0" upper_limit="32.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race/Ethnicity</title>
              <category_list>
                <category>
                  <title>African American/Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Caucasian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Difference in Pain Score as Measured by a Visual Analogue Scale (VAS)</title>
        <description>Each ED study visit was the unit of analysis for the statistical methods addressing the primary outcome. The primary outcome was change in pain score from arrival to discharge. Pain severity was assessed at arrival and discharge from ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating &quot;no pain&quot; and 100 indicating &quot;pain as bad as it could be&quot; or &quot;worst imaginable pain&quot;.Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED. Thus, the difference in pain scores were calculated as the arrival minus discharge VAS scores, with higher positive pain difference or change scores indicating greater pain reduction.</description>
        <time_frame>Arrival in ED to discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Difference in Pain Score as Measured by a Visual Analogue Scale (VAS)</title>
          <description>Each ED study visit was the unit of analysis for the statistical methods addressing the primary outcome. The primary outcome was change in pain score from arrival to discharge. Pain severity was assessed at arrival and discharge from ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating &quot;no pain&quot; and 100 indicating &quot;pain as bad as it could be&quot; or &quot;worst imaginable pain&quot;.Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED. Thus, the difference in pain scores were calculated as the arrival minus discharge VAS scores, with higher positive pain difference or change scores indicating greater pain reduction.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
          <units>Units on a 100 mm VAS</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.4" spread="10.6"/>
                    <measurement group_id="O2" value="43.0" spread="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Change in pain scores from arrival to discharge</non_inferiority_desc>
            <p_value>0.0311</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Analysis for pain change was conducted using Hierarchical Linear Mixed Effects Model (HLM), adjusting for nested patient and site effects (N=126)</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Pain Visual Analogue Scale (VAS) Scores Over Time</title>
        <description>Pain severity was assessed at arrival and every 30 minutes until discharge from the ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating &quot;no pain&quot; and 100 indicating &quot;pain as bad as it could be&quot; or &quot;worst imaginable pain&quot;. Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED.&#xD;
A hierarchical random coefficients regression model for repeated measurements (type of mixed hierarchical mixed-effect model) was conducted on the pain scores collected at six time points (arrival, post-placement 30-min, 60-min, 90-min,120-min, discharge) to evaluate the trajectory of change in pain. Discharge occurred at 120 minutes or later during each visit, with the exception of one discharge at 54 minutes.</description>
        <time_frame>Every 30 minutes from arrival in ED to discharge from the ED, up to 6 hours</time_frame>
        <population>The entire observation period was not evaluated because the patient-specific protocol has a shorter time to discharge, and, there was data missing at random after 120 minutes. To avoid a biased result, the mixed model was conducted on the data collected every 30 minutes during initial 120 minutes (2 hours) and at discharge.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pain Visual Analogue Scale (VAS) Scores Over Time</title>
          <description>Pain severity was assessed at arrival and every 30 minutes until discharge from the ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating &quot;no pain&quot; and 100 indicating &quot;pain as bad as it could be&quot; or &quot;worst imaginable pain&quot;. Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED.&#xD;
A hierarchical random coefficients regression model for repeated measurements (type of mixed hierarchical mixed-effect model) was conducted on the pain scores collected at six time points (arrival, post-placement 30-min, 60-min, 90-min,120-min, discharge) to evaluate the trajectory of change in pain. Discharge occurred at 120 minutes or later during each visit, with the exception of one discharge at 54 minutes.</description>
          <population>The entire observation period was not evaluated because the patient-specific protocol has a shorter time to discharge, and, there was data missing at random after 120 minutes. To avoid a biased result, the mixed model was conducted on the data collected every 30 minutes during initial 120 minutes (2 hours) and at discharge.</population>
          <units>Units on a 100 mm VAS</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Emergency Department Arrival</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.2" spread="13.0"/>
                    <measurement group_id="O2" value="82.2" spread="17.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-placement 30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.6" spread="13.1"/>
                    <measurement group_id="O2" value="79.6" spread="17.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-placement 60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.0" spread="13.4"/>
                    <measurement group_id="O2" value="77.2" spread="17.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-placement 90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.4" spread="13.7"/>
                    <measurement group_id="O2" value="74.7" spread="17.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-placement 120 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.9" spread="14.0"/>
                    <measurement group_id="O2" value="72.2" spread="17.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emergency Department Discharge</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.7" spread="21.9"/>
                    <measurement group_id="O2" value="40.9" spread="25.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The trajectory of change in pain score was evaluated every 30 minutes over 120 hours (2 hours) rather than 6 hours because of expected missing data after 120 minutes due to discharge from the ED.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Trajectory of pain across time (arrival to discharge)</non_inferiority_desc>
            <p_value>0.0049</p_value>
            <p_value_desc>p-value for the protocol by time interaction</p_value_desc>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Emergency Department Arrival</non_inferiority_desc>
            <p_value>0.9393</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Post-placement 30 minutes</non_inferiority_desc>
            <p_value>0.7259</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Post-placement 60 minutes</non_inferiority_desc>
            <p_value>0.5300</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Post-placement 90 minutes</non_inferiority_desc>
            <p_value>0.3678</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Post-placement 120 minutes</non_inferiority_desc>
            <p_value>0.2457</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Emergency Department Discharge</non_inferiority_desc>
            <p_value>0.0007</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Nausea During Emergency Department Visits</title>
        <description>Nausea at any point from placement until discharge, based on nausea data collected every 30 minutes during that time period. Thus, a nausea variable was derived in which 0=no and 1=yes that nausea was reported by the patient at least once during the placement to discharge time interval.</description>
        <time_frame>From placement in Emergency Department (ED) treatment room to discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods.</population>
        <group_list>
          <group group_id="O1">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
          <group group_id="O2">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Nausea During Emergency Department Visits</title>
          <description>Nausea at any point from placement until discharge, based on nausea data collected every 30 minutes during that time period. Thus, a nausea variable was derived in which 0=no and 1=yes that nausea was reported by the patient at least once during the placement to discharge time interval.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Nausea - No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Nausea - Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Incidence of nausea during Emergency Department Visit - YES</non_inferiority_desc>
            <p_value>0.0001</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Vomiting During Emergency Department Visits</title>
        <description>Vomiting at any point from placement until discharge, based on vomiting data collected every 30 minutes during that time period. Thus, a vomiting variable was derived in which 0=no and 1=yes that vomiting was reported by the patient at least once during the placement to discharge time interval.</description>
        <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Vomiting During Emergency Department Visits</title>
          <description>Vomiting at any point from placement until discharge, based on vomiting data collected every 30 minutes during that time period. Thus, a vomiting variable was derived in which 0=no and 1=yes that vomiting was reported by the patient at least once during the placement to discharge time interval.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Vomiting - No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="54"/>
                    <measurement group_id="O2" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Vomiting - Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Incidence of vomiting (YES) during Emergency Department visit</non_inferiority_desc>
            <p_value>0.6625</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of a Decrease in Systolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit</title>
        <description>Decrease in systolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A systolic variable was derived in which 0=no and 1=yes that a &gt;= 20% decrease of baseline systolic blood pressure was reported by the patient at least once during the placement to discharge time interval.</description>
        <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of a Decrease in Systolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit</title>
          <description>Decrease in systolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A systolic variable was derived in which 0=no and 1=yes that a &gt;= 20% decrease of baseline systolic blood pressure was reported by the patient at least once during the placement to discharge time interval.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Decrease in systolic BP - No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="55"/>
                    <measurement group_id="O2" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Decrease in systolic BP - Y</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Decrease in systolic BP (&gt;= 20% of baseline)</non_inferiority_desc>
            <p_value>0.4473</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of a Decrease in Diastolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit</title>
        <description>Decrease in diastolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A diastolic variable was derived in which 0=no and 1=yes that a &gt; 20% decrease of baseline diastolic blood pressure was reported by the patient at least once during the placement to discharge time interval.</description>
        <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of a Decrease in Diastolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit</title>
          <description>Decrease in diastolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A diastolic variable was derived in which 0=no and 1=yes that a &gt; 20% decrease of baseline diastolic blood pressure was reported by the patient at least once during the placement to discharge time interval.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Decrease in diastolic BP - No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Decrease in diastolic BP - Y</title>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Decrease in diastolic blood pressure (&gt;= 20% baseline)</non_inferiority_desc>
            <p_value>0.5372</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Oxygen Desaturation (&lt; 95%) (YES) During Emergency Department Visit</title>
        <description>Saturation of peripheral capillary oxygen &lt; 95% (SPO2 &lt; 95%) at any point from placement until discharge, based on SPO2 data collected every 30 minutes during that time period. Thus, a SPO2 variable was derived in which 0=no and 1=yes that SPO2 &lt; 95% was reported by the patient at least once during the placement to discharge time interval.</description>
        <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Oxygen Desaturation (&lt; 95%) (YES) During Emergency Department Visit</title>
          <description>Saturation of peripheral capillary oxygen &lt; 95% (SPO2 &lt; 95%) at any point from placement until discharge, based on SPO2 data collected every 30 minutes during that time period. Thus, a SPO2 variable was derived in which 0=no and 1=yes that SPO2 &lt; 95% was reported by the patient at least once during the placement to discharge time interval.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>SpO2 &lt; 95% - No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>SpO2 &lt; 95% - Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Incidence of oxygen desaturation (&lt;95%) YES during Emergency Department visit</non_inferiority_desc>
            <p_value>0.2891</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Respiratory Distress (YES) During Emergency Department Visit</title>
        <description>Respiratory distress at any point from placement until discharge, based on data collected every 30 minutes during that time period. Thus, a respiratory distress variable was derived in which 0=no and 1=yes that respiratory distress was reported by the patient at least once during the placement to discharge time interval.</description>
        <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Respiratory Distress (YES) During Emergency Department Visit</title>
          <description>Respiratory distress at any point from placement until discharge, based on data collected every 30 minutes during that time period. Thus, a respiratory distress variable was derived in which 0=no and 1=yes that respiratory distress was reported by the patient at least once during the placement to discharge time interval.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Respiratory Distress - No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="64"/>
                    <measurement group_id="O2" value="62"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Respiratory Distress - Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Sedation During Emergency Department Visit</title>
        <description>Severe-to moderate sedation at any point from placement until discharge, based on sedation data collected every 30 minutes during that time period. Thus, a sedation variable was derived in which 0=no and 1=yes that moderate-severe sedation was reported by the patient at least once during the placement to discharge time interval. Sedations scoring was as follows: None was defined as &quot;awake and alert&quot;, Mild sedation was defined as &quot;responds to voice&quot;, Moderate sedation was defined as &quot;responds to touch, with or without voice&quot; and Severe sedation was defined as &quot;somnolent, difficult to arouse&quot;.</description>
        <time_frame>From placement in ED treatment room to discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Sedation During Emergency Department Visit</title>
          <description>Severe-to moderate sedation at any point from placement until discharge, based on sedation data collected every 30 minutes during that time period. Thus, a sedation variable was derived in which 0=no and 1=yes that moderate-severe sedation was reported by the patient at least once during the placement to discharge time interval. Sedations scoring was as follows: None was defined as &quot;awake and alert&quot;, Mild sedation was defined as &quot;responds to voice&quot;, Moderate sedation was defined as &quot;responds to touch, with or without voice&quot; and Severe sedation was defined as &quot;somnolent, difficult to arouse&quot;.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>none to mild sedation</title>
                  <measurement_list>
                    <measurement group_id="O1" value="51"/>
                    <measurement group_id="O2" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>moderate to severe sedation</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Incidence of sedation during Emergency Department visit.</non_inferiority_desc>
            <p_value>0.3915</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of the Need for Supplemental Oxygen During Emergency Department Visit</title>
        <description>Need for supplemental oxygen during the Emergency Department stay; this was determined at discharge.</description>
        <time_frame>Following the initiation of opioid therapy until discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of the Need for Supplemental Oxygen During Emergency Department Visit</title>
          <description>Need for supplemental oxygen during the Emergency Department stay; this was determined at discharge.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>O2 needed - No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>O2 needed - Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Incidence of the need for supplemental oxygen during Emergency Department visit</non_inferiority_desc>
            <p_value>0.0726</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of the Administration of Naloxone During Emergency Department Visit</title>
        <description>Naloxone administered during the Emergency Department stay; this was determined at discharge.</description>
        <time_frame>Following the initiation of opioid therapy until discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of the Administration of Naloxone During Emergency Department Visit</title>
          <description>Naloxone administered during the Emergency Department stay; this was determined at discharge.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Naloxone administered - No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="64"/>
                    <measurement group_id="O2" value="62"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Naloxone administered - Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of the Need for Assistive Ventilation</title>
        <description>Intubation or other assistive ventilation techniques - including bag, valve, or mask was performed during the ED stay; this was determined at discharge.</description>
        <time_frame>Following the initiation of opioid therapy until discharge from the ED, up to 6 hours</time_frame>
        <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
          </group>
          <group group_id="O2">
            <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
            <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of the Need for Assistive Ventilation</title>
          <description>Intubation or other assistive ventilation techniques - including bag, valve, or mask was performed during the ED stay; this was determined at discharge.</description>
          <population>Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.</population>
          <units>Emergency Department Visits</units>
          <param>Count of Units</param>
          <units_analyzed>Emergency Department Visits</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Emergency Department Visits</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="64"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Assistive Ventilation - No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="64"/>
                    <measurement group_id="O2" value="62"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Assistive Ventilation - Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected on study subjects from time of admission to the Emergency Department until discharge from the Emergency Department, decision to admit to hospital, or up to 6 hours, whichever came first.</time_frame>
      <desc>Adverse Events were defined as intubation and/or admission to the Intensive Care Unit.</desc>
      <group_list>
        <group group_id="E1">
          <title>Patient Specific Dose of Morphine Sulfate or Hydromorphone</title>
          <description>A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.&#xD;
Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.&#xD;
Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.</description>
        </group>
        <group group_id="E2">
          <title>Standard Dose of Morphine Sulfate or Hydromorphone</title>
          <description>A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.&#xD;
Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).&#xD;
Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Paula Tanabe</name_or_title>
      <organization>Duke University</organization>
      <phone>919-613-6038</phone>
      <email>paula.tanabe@duke.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02222246
org study id: Pro00054047
secondary id: R34 RHL121224A
nct id: NCT02222246
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The goal of this pilot study is to improve emergency department (ED) pain management for
      adults with sickle cell disease. Sickle cell disease (SCD) is the most common genetic
      disorder in the United States, and occurs primarily among African Americans. Management of
      painful episodes associated with SCD, referred to as vaso-occlusive crises (VOC), is the most
      common reason for SCD patients to visit the ED. Currently, there is no standard approach to
      managing VOC pain in the ED that is widely accepted and used, and pain management for
      vaso-occlusive crisis in persons with SCD is very different between providers and not based
      on research. Many times, patients who come to the ED with sickle cell pain feel that they do
      not receive adequate pain control. If EDs could provide efficient, effective, safe,
      patient-centered analgesic management, it may be possible to improve pain management for
      adults with SCD experiencing a VOC. Guidelines for treating vaso-occlusive crises caused by
      sickle cell disease will soon be published by the National Heart, Lung and Blood Institute of
      the National Institutes of Health. These guidelines recommend patient-specific pain treatment
      protocols or a standardized pain management protocol for SCD when a patient does not already
      have a pain treatment protocol designed for them. The purpose of this pilot study is to
      compare these two ways to treat vaso-occlusive pain in the ED for adults with sickle cell
      disease, and to determine if a large randomized controlled trial is feasible and required.
In August 2012 the National Heart, Lung, and Blood Institute (NHBLI) released for public
      comment their "Management of Sickle Cell Disease" evidence-based recommendations that were
      developed with consensus panel expertise. Because of a lack of empirical data, most of the
      recommendations specific to vaso-occlusive crises (VOC) were based on consensus panel
      expertise. Recommendations included the use of a patient-specific protocol (specific agents
      and doses for an individual patient). While many attempts have been made to implement
      patient-specific analgesic protocols for use in emergency departments (EDs), anecdotally,
      these have been difficult to implement and maintain over time; a practical approach to
      development, implementation, and dissemination has not been determined. As patient-specific
      protocols are not available in most EDs, the guidelines go on to recommend a SCD specific
      standard analgesic protocol. Both of these recommended protocols provide more aggressive VOC
      pain management than a typical generic ED pain protocol. However, there is an urgent need to
      rigorously test the NHLBI recommendations and compare the two approaches for managing VOC in
      the ED. A large randomized clinical trial (RCT) is essential to test these protocols.

      This pilot project will compare these two different, evidence-based, protocols which include
      opioid pain medicines routinely used as standard of care to treat VOC pain in the ED for
      individuals with SCD, and collect the data necessary to determine if a large RCT is feasible
      and required. This study is novel in that it will design an approach to develop and implement
      patient-specific and standard analgesic VOC protocols for use in the ED, will develop a
      bundle of information technology and education interventions to enhance protocol adoption for
      the pilot RCT, and also be the first RCT conducted in an ED setting to compare two different
      ED pain management protocols for SCD patients who experience a VOC.

      The study consists of 3 aims:

        1. Develop and implement patient specific VOC protocols for patients randomized to this
           arm,

        2. Conduct a pilot RCT to determine the necessary sample size needed for a large RCT to
           compare the difference in reduction in pain score from ED arrival to discharge,
           hospitalization, clinical and safety outcomes, between subjects assigned randomly to
           either a standard SCD analgesic protocol or to a patient-specific analgesic protocol,

        3. Measure feasibility of methods and acceptability of and fidelity to protocols by
           evaluating optimal recruitment and retention strategies, and assessing ED providers
           perceptions of facilitators and barriers to protocol use and protocol adherence.

      The soon to be published NHBLI guidelines for managing SCD will be used as the standard
      protocol with the modification of basing the initial dose of pain medicine on patient weight.
      The standard protocol will recommend re-assessment, and re-dosing with possible dose
      escalation, every 20-30 minutes. Repeat doses for patients randomized to the weight-based
      protocol, when necessary, will be maintained or provided at 1 dose level increase (no more
      than 25%) above the initial dose. For patients randomized to the patient -specific protocol,
      the SCD provider has experience with the individual patient and is best qualified to make
      dosing and frequency recommendations based upon doses required during past ED and hospital
      visits for treatment of VOC, and on daily opioid use if applicable. There is no set maximum
      dose for patients randomized to the patient-specific protocols.

      Both the patient-specific and standard protocols will be available in the ED via a patient's
      electronic medical record. Upon ED arrival, providers will retrieve the patient's study
      protocol (patient-specific, or standard) which will include the starting agents, and doses,
      the subsequent analgesic recommendations, and order medications according to the
      pre-determined protocol.

      The study will be conducted at the emergency departments of the University of Cincinnati
      Medical Center and the Mt. Sinai Hospital in New York. Patients will be enrolled in the study
      for up to 12-months, but may contribute no more that five different ED visits for VOC pain
      control during enrollment to allow for a larger number of different patients.

      Study outcomes will be compared between ED visits of patients randomized to a
      patient-specific vs. a standard SCD protocol. The primary outcome will be the difference in
      pain score from ED arrival to discharge, up to 6 hours, as measured using a visual analogue
      scale. The trajectories of average pain scores from immediately prior to administration of
      1st analgesic dose to discharge by 30 minute increments for each treatment group will also be
      calculated.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Difference in Pain Score as Measured by a Visual Analogue Scale (VAS)
time frame: Arrival in ED to discharge from the ED, up to 6 hours
description: Each ED study visit was the unit of analysis for the statistical methods addressing the primary outcome. The primary outcome was change in pain score from arrival to discharge. Pain severity was assessed at arrival and discharge from ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating "no pain" and 100 indicating "pain as bad as it could be" or "worst imaginable pain".Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED. Thus, the difference in pain scores were calculated as the arrival minus discharge VAS scores, with higher positive pain difference or change scores indicating greater pain reduction.
measure: Change in Pain Visual Analogue Scale (VAS) Scores Over Time
time frame: Every 30 minutes from arrival in ED to discharge from the ED, up to 6 hours
description: Pain severity was assessed at arrival and every 30 minutes until discharge from the ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating "no pain" and 100 indicating "pain as bad as it could be" or "worst imaginable pain". Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED.
A hierarchical random coefficients regression model for repeated measurements (type of mixed hierarchical mixed-effect model) was conducted on the pain scores collected at six time points (arrival, post-placement 30-min, 60-min, 90-min,120-min, discharge) to evaluate the trajectory of change in pain. Discharge occurred at 120 minutes or later during each visit, with the exception of one discharge at 54 minutes.
measure: Incidence of Nausea During Emergency Department Visits
time frame: From placement in Emergency Department (ED) treatment room to discharge from the ED, up to 6 hours
description: Nausea at any point from placement until discharge, based on nausea data collected every 30 minutes during that time period. Thus, a nausea variable was derived in which 0=no and 1=yes that nausea was reported by the patient at least once during the placement to discharge time interval.
measure: Incidence of Vomiting During Emergency Department Visits
time frame: From placement in ED treatment room to discharge from the ED, up to 6 hours
description: Vomiting at any point from placement until discharge, based on vomiting data collected every 30 minutes during that time period. Thus, a vomiting variable was derived in which 0=no and 1=yes that vomiting was reported by the patient at least once during the placement to discharge time interval.
measure: Incidence of a Decrease in Systolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit
time frame: From placement in ED treatment room to discharge from the ED, up to 6 hours
description: Decrease in systolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A systolic variable was derived in which 0=no and 1=yes that a >= 20% decrease of baseline systolic blood pressure was reported by the patient at least once during the placement to discharge time interval.
measure: Incidence of a Decrease in Diastolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit
time frame: From placement in ED treatment room to discharge from the ED, up to 6 hours
description: Decrease in diastolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A diastolic variable was derived in which 0=no and 1=yes that a > 20% decrease of baseline diastolic blood pressure was reported by the patient at least once during the placement to discharge time interval.
measure: Incidence of Oxygen Desaturation (< 95%) (YES) During Emergency Department Visit
time frame: From placement in ED treatment room to discharge from the ED, up to 6 hours
description: Saturation of peripheral capillary oxygen < 95% (SPO2 < 95%) at any point from placement until discharge, based on SPO2 data collected every 30 minutes during that time period. Thus, a SPO2 variable was derived in which 0=no and 1=yes that SPO2 < 95% was reported by the patient at least once during the placement to discharge time interval.
measure: Incidence of Respiratory Distress (YES) During Emergency Department Visit
time frame: From placement in ED treatment room to discharge from the ED, up to 6 hours
description: Respiratory distress at any point from placement until discharge, based on data collected every 30 minutes during that time period. Thus, a respiratory distress variable was derived in which 0=no and 1=yes that respiratory distress was reported by the patient at least once during the placement to discharge time interval.
measure: Incidence of Sedation During Emergency Department Visit
time frame: From placement in ED treatment room to discharge from the ED, up to 6 hours
description: Severe-to moderate sedation at any point from placement until discharge, based on sedation data collected every 30 minutes during that time period. Thus, a sedation variable was derived in which 0=no and 1=yes that moderate-severe sedation was reported by the patient at least once during the placement to discharge time interval. Sedations scoring was as follows: None was defined as "awake and alert", Mild sedation was defined as "responds to voice", Moderate sedation was defined as "responds to touch, with or without voice" and Severe sedation was defined as "somnolent, difficult to arouse".
measure: Incidence of the Need for Supplemental Oxygen During Emergency Department Visit
time frame: Following the initiation of opioid therapy until discharge from the ED, up to 6 hours
description: Need for supplemental oxygen during the Emergency Department stay; this was determined at discharge.
measure: Incidence of the Administration of Naloxone During Emergency Department Visit
time frame: Following the initiation of opioid therapy until discharge from the ED, up to 6 hours
description: Naloxone administered during the Emergency Department stay; this was determined at discharge.
measure: Incidence of the Need for Assistive Ventilation
time frame: Following the initiation of opioid therapy until discharge from the ED, up to 6 hours
description: Intubation or other assistive ventilation techniques - including bag, valve, or mask was performed during the ED stay; this was determined at discharge.
arm group label: Patient Specific dose of Morphine Sulfate or Hydromorphone
arm group type: Experimental
description: A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 5 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.
arm group label: Standard dose of Morphine Sulfate or Hydromorphone
arm group type: Active Comparator
description: A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.
intervention type: Drug
intervention name: Hydromorphone (Standardized, weight-based dosing)
description: Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).
arm group label: Standard dose of Morphine Sulfate or Hydromorphone
other name: Dilaudid
intervention type: Drug
intervention name: Morphine Sulfate (Standardized, weight-based dosing)
description: Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).
arm group label: Standard dose of Morphine Sulfate or Hydromorphone
intervention type: Drug
intervention name: Hydromorphone (Patient Specific dosing)
description: Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.
arm group label: Patient Specific dose of Morphine Sulfate or Hydromorphone
other name: Dilaudid
intervention type: Drug
intervention name: Morphine Sulfate (Patient Specific dosing)
description: Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.
arm group label: Patient Specific dose of Morphine Sulfate or Hydromorphone
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Paula Tanabe, PhD
role: Principal Investigator
affiliation: Duke University School of Nursing
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
mesh term: Acute Pain
mesh term: Morphine
mesh term: Hydromorphone
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 