<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/NCT02219659</url>
  </required_header>
  <id_info>
    <org_study_id>25613</org_study_id>
    <nct_id>NCT02219659</nct_id>
  </id_info>
  <brief_title>Pilot Study on Pairing Sedation Strategies and Weaning</brief_title>
  <official_title>Comparing Strategies of Pairing Sedation and Weaning Protocols on Outcomes of Mechanical Ventilation: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MemorialCare Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Memorial Medical Center Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>MemorialCare Health System</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A three-arm, randomized, pilot feasibility, study to assess the effect three validated&#xD;
      sedation strategies on outcomes of patient on mechanical ventilation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A three-arm, randomized, pilot feasibility, study to assess the effect three validated&#xD;
      sedation strategies on outcomes of patient on mechanical ventilation.&#xD;
&#xD;
      A significant proportion of patients admitted to the intensive care unit (ICU) require&#xD;
      mechanical ventilation (MV). To maintain comfort and facilitate quality care, large&#xD;
      quantities of sedatives and analgesics are often administered either by continuous infusion,&#xD;
      with or without daily interruption (DI) of sedation, or as intermittent doses of analgesics.&#xD;
      Three validated sedation strategies are currently available. A recently published study (&#xD;
      trial has shown that instituting protocol-directed sedation in patients requiring continuous&#xD;
      infusion of sedatives and analgesics, whether or not daily interruption (DI) of the sedative&#xD;
      occurs, will improve MV outcomes, specifically the duration of MV. Girard et al performed a&#xD;
      randomized, multicenter, clinical trial (ABC- Awakening and Breathing Controlled trial)&#xD;
      evaluating the pairing of a spontaneous awakening trial (SAT) with an SBT. Most recently, a&#xD;
      Danish study by Strom et al. investigated whether an analgesia-first approach to patient&#xD;
      comfort that consisted of intermittent doses of intravenous opioids, and the initiation of IV&#xD;
      sedation for short periods only when acute agitation was present, would be superior to a&#xD;
      protocol similar to the ABC trial. While the three above mentioned approaches are accepted&#xD;
      and currently implemented in the critical care community there is no comparative study or&#xD;
      evaluation on the optimal timing to conduct a spontaneous breathing trial (SBT) for assessing&#xD;
      weaning readiness with each of these strategies. It is possible that a SAT strategy, where&#xD;
      sedative and opioid infusions are interrupted, may lead to more agitation and anxiety than a&#xD;
      strategy in patients managed with a sedation protocol where intravenous sedative and&#xD;
      analgesic therapy is regularly titrated to maintain patients in a lightly sedated state.&#xD;
      Moreover, it remains unclear whether there are advantages of an analgesia-first sedation&#xD;
      strategy over either an SAT or sedation protocol strategy in terms of the time it takes to&#xD;
      wean patients from MV. However, it is noteworthy to mention that the analgesia-first strategy&#xD;
      was associated with more delirium episodes, which were attributed to the ability to assess&#xD;
      for it in a more awake patient. However, comparing delirium occurrence in studies with&#xD;
      different sedation goals and methodologies may be inaccurate.&#xD;
&#xD;
      The investigators therefore propose a three-arm, randomized, pilot feasibility, study to&#xD;
      assess the effect of these three (3) validated strategies for sedation and pain management&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">April 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determining the feasibility of conducting the study protocol</measure>
    <time_frame>Up to 180 days</time_frame>
    <description>This is the rate on enrollment and number of protocol non-adherence</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mechanical ventilation free days</measure>
    <time_frame>Up to 180 days</time_frame>
    <description>This is the number of days where patients were breathing without assistance during the study period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of weaning</measure>
    <time_frame>Up to 180 days</time_frame>
    <description>Time from initiation of weaning until successful extubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>Up to 180 days</time_frame>
    <description>The number of days from ICU admission to ICU discharge</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Acute Respiratory Failure</condition>
  <arm_group>
    <arm_group_label>Sedation protocol with interruption</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Every morning both drugs are stopped (Daily Interruption) and patient's wakefulness is assessed per protocol. If patient's pain and RASS score stays within the target, both drugs are kept off. If patient shows any signs and symptoms of pain or agitation (described in the study protocol), both drugs are restarted at a half dose of the previous dose and titrated to target pain and RASS score. Every morning both drugs are stopped and when patient is awake and met the SBT safety screen, 120-min continuous positive airway pressure (CPAP) trial is performed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sedation protocol without Interruption</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Daily interruption of fentanyl and midazolam is not performed. Every morning 120-min CPAP trial is performed as long as the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fentanyl push first</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This arm attempts to manage patient's pain and agitation with analgesia first. Fentanyl intravenous (IV) pushes are administered every 5 minutes as needed to target pain and sedation score, up to 4 doses per hour. Every morning 120-min CPAP trial is performed as long as patient's RASS score is 0 to -2 and patient passes the SBT safety screen. If fentanyl IV push doses alone cannot manage patient's pain and agitation (could not reach the target score), notify the study team. Fentanyl infusion is started and titrated to target pain and sedation score up to 6 hours. If fentanyl infusion is titrated up twice consecutively and target pain and sedation score are not met, notify the study team. Propofol infusion is started and titrated to target RASS score up to 6 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sedation Protocol with Daily Interruption</intervention_name>
    <description>Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning both infusions are stopped and when the patient is awake and met the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.</description>
    <arm_group_label>Sedation protocol with interruption</arm_group_label>
    <other_name>fentanyl</other_name>
    <other_name>midazolam</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sedation Protocol Without Daily Interruption</intervention_name>
    <description>Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.</description>
    <arm_group_label>Sedation protocol without Interruption</arm_group_label>
    <other_name>fentanyl</other_name>
    <other_name>midazolam</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl Push First</intervention_name>
    <description>Fentanyl 25 mcg intravenous push (IVP) every 5 min up to 4 doses hourly as needed to target pain score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when patient's RASS is 0 to -2 and passes the SBT safety screen, 120-min CPAP trial is performed. If patient meets CPAP passing criteria, the physician will be notified for determination of extubation. If patient does not pass, it is repeated next morning. If target RASS is not achieved with fentanyl IV push alone, study team is notified and fentanyl infusion at 50 mcg/hr titrated by 25 mcg/hr every 30 min to target pain score (max 6 hrs). If target RASS score is not achieved with the fentanyl IV, propofol infusion is started at 5 mcg/kg/hr titrated by 5 mcg/kg/hr every 15 min to target RASS score (max 6 hrs).</description>
    <arm_group_label>Fentanyl push first</arm_group_label>
    <other_name>fentanyl</other_name>
    <other_name>propofol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ≥ 18 years of age&#xD;
&#xD;
          2. Mechanically ventilated with an expected duration of MV ≥ 48 hours&#xD;
&#xD;
          3. ICU team has initiated continuous sedative and/or /analgesic infusions&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Admission after resuscitation from cardiac arrest&#xD;
&#xD;
          2. Admission with traumatic brain injury or another acute neurologic event (e,g. stroke,&#xD;
             uncontrolled seizures).&#xD;
&#xD;
          3. History of severe dementia&#xD;
&#xD;
          4. Admission because of acute alcohol withdrawal or acute drug intoxication&#xD;
&#xD;
          5. Administration of more than 24 hours of continuous sedation&#xD;
&#xD;
          6. Allergy to fentanyl, midazolam, and/or propofol&#xD;
&#xD;
          7. Lack of informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maged Tanios, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Long Beach Memorial Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Long Beach Memorial Medical Center</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>February 20, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <last_update_submitted>March 11, 2019</last_update_submitted>
  <last_update_submitted_qc>March 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sedation strategy</keyword>
  <keyword>mechanical ventilation</keyword>
  <keyword>ventilator weaning</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Propofol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 19, 2020</submitted>
    <returned>September 4, 2020</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02219659
org study id: 25613
nct id: NCT02219659
lead sponsor: 
collaborator: 
has dmc: Yes
A three-arm, randomized, pilot feasibility, study to assess the effect three validated
      sedation strategies on outcomes of patient on mechanical ventilation.
A three-arm, randomized, pilot feasibility, study to assess the effect three validated
      sedation strategies on outcomes of patient on mechanical ventilation.

      A significant proportion of patients admitted to the intensive care unit (ICU) require
      mechanical ventilation (MV). To maintain comfort and facilitate quality care, large
      quantities of sedatives and analgesics are often administered either by continuous infusion,
      with or without daily interruption (DI) of sedation, or as intermittent doses of analgesics.
      Three validated sedation strategies are currently available. A recently published study (
      trial has shown that instituting protocol-directed sedation in patients requiring continuous
      infusion of sedatives and analgesics, whether or not daily interruption (DI) of the sedative
      occurs, will improve MV outcomes, specifically the duration of MV. Girard et al performed a
      randomized, multicenter, clinical trial (ABC- Awakening and Breathing Controlled trial)
      evaluating the pairing of a spontaneous awakening trial (SAT) with an SBT. Most recently, a
      Danish study by Strom et al. investigated whether an analgesia-first approach to patient
      comfort that consisted of intermittent doses of intravenous opioids, and the initiation of IV
      sedation for short periods only when acute agitation was present, would be superior to a
      protocol similar to the ABC trial. While the three above mentioned approaches are accepted
      and currently implemented in the critical care community there is no comparative study or
      evaluation on the optimal timing to conduct a spontaneous breathing trial (SBT) for assessing
      weaning readiness with each of these strategies. It is possible that a SAT strategy, where
      sedative and opioid infusions are interrupted, may lead to more agitation and anxiety than a
      strategy in patients managed with a sedation protocol where intravenous sedative and
      analgesic therapy is regularly titrated to maintain patients in a lightly sedated state.
      Moreover, it remains unclear whether there are advantages of an analgesia-first sedation
      strategy over either an SAT or sedation protocol strategy in terms of the time it takes to
      wean patients from MV. However, it is noteworthy to mention that the analgesia-first strategy
      was associated with more delirium episodes, which were attributed to the ability to assess
      for it in a more awake patient. However, comparing delirium occurrence in studies with
      different sedation goals and methodologies may be inaccurate.

      The investigators therefore propose a three-arm, randomized, pilot feasibility, study to
      assess the effect of these three (3) validated strategies for sedation and pain management
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determining the feasibility of conducting the study protocol
time frame: Up to 180 days
description: This is the rate on enrollment and number of protocol non-adherence
measure: Mechanical ventilation free days
time frame: Up to 180 days
description: This is the number of days where patients were breathing without assistance during the study period.
measure: Duration of weaning
time frame: Up to 180 days
description: Time from initiation of weaning until successful extubation
measure: ICU length of stay
time frame: Up to 180 days
description: The number of days from ICU admission to ICU discharge
arm group label: Sedation protocol with interruption
arm group type: Active Comparator
description: Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Every morning both drugs are stopped (Daily Interruption) and patient's wakefulness is assessed per protocol. If patient's pain and RASS score stays within the target, both drugs are kept off. If patient shows any signs and symptoms of pain or agitation (described in the study protocol), both drugs are restarted at a half dose of the previous dose and titrated to target pain and RASS score. Every morning both drugs are stopped and when patient is awake and met the SBT safety screen, 120-min continuous positive airway pressure (CPAP) trial is performed.
arm group label: Sedation protocol without Interruption
arm group type: Active Comparator
description: Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Daily interruption of fentanyl and midazolam is not performed. Every morning 120-min CPAP trial is performed as long as the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen.
arm group label: Fentanyl push first
arm group type: Active Comparator
description: This arm attempts to manage patient's pain and agitation with analgesia first. Fentanyl intravenous (IV) pushes are administered every 5 minutes as needed to target pain and sedation score, up to 4 doses per hour. Every morning 120-min CPAP trial is performed as long as patient's RASS score is 0 to -2 and patient passes the SBT safety screen. If fentanyl IV push doses alone cannot manage patient's pain and agitation (could not reach the target score), notify the study team. Fentanyl infusion is started and titrated to target pain and sedation score up to 6 hours. If fentanyl infusion is titrated up twice consecutively and target pain and sedation score are not met, notify the study team. Propofol infusion is started and titrated to target RASS score up to 6 hours.
intervention type: Drug
intervention name: Sedation Protocol with Daily Interruption
description: Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning both infusions are stopped and when the patient is awake and met the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.
arm group label: Sedation protocol with interruption
other name: fentanyl
other name: midazolam
intervention type: Drug
intervention name: Sedation Protocol Without Daily Interruption
description: Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.
arm group label: Sedation protocol without Interruption
other name: fentanyl
other name: midazolam
intervention type: Drug
intervention name: Fentanyl Push First
description: Fentanyl 25 mcg intravenous push (IVP) every 5 min up to 4 doses hourly as needed to target pain score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when patient's RASS is 0 to -2 and passes the SBT safety screen, 120-min CPAP trial is performed. If patient meets CPAP passing criteria, the physician will be notified for determination of extubation. If patient does not pass, it is repeated next morning. If target RASS is not achieved with fentanyl IV push alone, study team is notified and fentanyl infusion at 50 mcg/hr titrated by 25 mcg/hr every 30 min to target pain score (max 6 hrs). If target RASS score is not achieved with the fentanyl IV, propofol infusion is started at 5 mcg/kg/hr titrated by 5 mcg/kg/hr every 15 min to target RASS score (max 6 hrs).
arm group label: Fentanyl push first
other name: fentanyl
other name: propofol
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maged Tanios, MD, MPH
role: Principal Investigator
affiliation: Long Beach Memorial Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Respiratory Insufficiency
mesh term: Fentanyl
mesh term: Midazolam
mesh term: Propofol
sharing ipd: Undecided
submitted: August 19, 2020
returned: September 4, 2020