<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/NCT03762317</url>
  </required_header>
  <id_info>
    <org_study_id>NAS</org_study_id>
    <nct_id>NCT03762317</nct_id>
  </id_info>
  <brief_title>Clonidine as Adjunct to Morphine for Neonatal Abstinence Syndrome</brief_title>
  <official_title>Clonidine as Adjunct to Morphine in the Management of Term and Near Term Infants With Neonatal Abstinence Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hennepin County Medical Center, Minneapolis</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hennepin County Medical Center, Minneapolis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective randomized double blinded study comparing the effect on duration of&#xD;
      pharmacologic treatment and duration of hospital stay when using clonidine at 12&#xD;
      µg/kilogram/day as an adjunct to oral morphine as compared to morphine monotherapy in the&#xD;
      management of term and near term infants with neonatal abstinence syndrome (NAS)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neonatal abstinence syndrome (NAS) is an emerging epidemic and has lead to a tremendous&#xD;
      increase in cost of medical care. Opioids are the mainstay of treatment for NAS although&#xD;
      there are concerns about possible short-term and long-term effects including but not limited&#xD;
      to adverse neurodevelopmental outcomes. Other drugs such as clonidine, phenobarbitone,&#xD;
      methadone and buprenorphine have been evaluated to limit the postnatal exposure to opioids in&#xD;
      these infants. Clonidine is an alpha 2 receptor and can lessen withdrawal manifestations. The&#xD;
      addition of clonidine at 6 µg/kilogram/day to morphine in the management of NAS has been&#xD;
      shown to reduce the duration of pharmacotherapy by about 27% in a previous study.&#xD;
&#xD;
      A recent pilot study reported reduction of treatment duration for NAS with clonidine (12&#xD;
      µg/kilogram/day) monotherapy as compared to morphine monotherapy. The study reported no&#xD;
      adverse effects in study subjects at the doses used in the study. The investigators&#xD;
      hypothesize that there will be a minimum of 30% reduction in the treatment duration with 12&#xD;
      µg/kilogram/day clonidine used as adjuncts to standard morphine treatment as compared to&#xD;
      morphine monotherapy in the management of term and near term infants with NAS&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study was initially suspended due to IND application and later terminated due to the difficulty&#xD;
    of obtaining consent during COVID period&#xD;
  </why_stopped>
  <start_date type="Actual">April 30, 2018</start_date>
  <completion_date type="Actual">December 12, 2018</completion_date>
  <primary_completion_date type="Actual">December 12, 2018</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Duration of Pharmacotherapy for NAS</measure>
    <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
    <description>The length of time in days from the initiation of pharmacotherapy on day 1 until the medication has been stopped</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Hospital Stay</measure>
    <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
    <description>Number of days spent in the hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Dose of Morphine Used</measure>
    <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
    <description>The maximum dose of morphine in mg/kg used for symptom control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Daily Dose of Oral Morphine Over Hospital Stay</measure>
    <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
    <description>The average daily dose of morphine used throughout study period in mg/kg/day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of Episodes of Heart Rate Variability (Heart Beats/Min)</measure>
    <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
    <description>Number of episodes of bradycardia (Heart rate &lt; 60/min for a minimum of 20 seconds and not associated with apnea or signs of reflux such as emesis, regurgitation of milk into the mouth or nose, arching while feeding, number of episodes of tachycardia (Heart rate &gt; 200/min) and not related to pain and/or agitation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of Episodes of Blood Pressure (mm of Hg) Variability</measure>
    <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
    <description>Number of episodes of hypotension (blood pressure &lt; 5th percentile for age) and hypertension (blood pressure &gt; 95th percentile for age)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Neonatal Abstinence Syndrome</condition>
  <arm_group>
    <arm_group_label>clonidine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo solution will be given for the duration of the study period</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clonidine</intervention_name>
    <description>clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
    <arm_group_label>clonidine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Requiring neonatal intensive care unit (NICU) admission for management of neonatal&#xD;
             abstinence syndrome&#xD;
&#xD;
          -  Gestational age greater than or equal to 36 weeks&#xD;
&#xD;
          -  Less than or equal to 48 hours of treatment with morphine for NAS&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of seizures&#xD;
&#xD;
          -  Congenital malformations, genetic syndromes or the presence of TORCH infections&#xD;
&#xD;
          -  Major medical problems&#xD;
&#xD;
          -  Heart rate and/or blood pressure instability&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>36 Weeks</minimum_age>
    <maximum_age>45 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>kunal gupta</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hennepin County Medical Center, Minneapolis</affiliation>
  </overall_official>
  <overall_official>
    <last_name>vinay sharma</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hennepin County Medical Center, Minneapolis</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hennepin County Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>November 8, 2017</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <results_first_submitted>November 21, 2022</results_first_submitted>
  <results_first_submitted_qc>January 26, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">February 10, 2023</results_first_posted>
  <last_update_submitted>January 26, 2023</last_update_submitted>
  <last_update_submitted_qc>January 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hennepin County Medical Center, Minneapolis</investigator_affiliation>
    <investigator_full_name>kunal gupta</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neonatal Abstinence Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clonidine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 30, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03762317/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>This was a randomized blinded study where the HCMC research pharmacist assigned the randomization group and provided the study medication and placebo</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Clonidine</title>
          <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period&#xD;
Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo solution will be given for the duration of the study period&#xD;
Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Clonidine</title>
          <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period&#xD;
Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo solution will be given for the duration of the study period&#xD;
Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</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="5"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39" lower_limit="37.3" upper_limit="42"/>
                    <measurement group_id="B2" value="37.4" lower_limit="36" upper_limit="39.1"/>
                    <measurement group_id="B3" value="38.3" lower_limit="36" upper_limit="42"/>
                  </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="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Duration of Pharmacotherapy for NAS</title>
        <description>The length of time in days from the initiation of pharmacotherapy on day 1 until the medication has been stopped</description>
        <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clonidine</title>
            <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period&#xD;
Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo solution will be given for the duration of the study period&#xD;
Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Pharmacotherapy for NAS</title>
          <description>The length of time in days from the initiation of pharmacotherapy on day 1 until the medication has been stopped</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.2" spread="18.6"/>
                    <measurement group_id="O2" value="25.6" spread="14.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Hospital Stay</title>
        <description>Number of days spent in the hospital</description>
        <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clonidine</title>
            <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period&#xD;
Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo solution will be given for the duration of the study period&#xD;
Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Hospital Stay</title>
          <description>Number of days spent in the hospital</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.4" spread="17.3"/>
                    <measurement group_id="O2" value="31.6" spread="13.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Dose of Morphine Used</title>
        <description>The maximum dose of morphine in mg/kg used for symptom control</description>
        <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clonidine</title>
            <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period&#xD;
Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo solution will be given for the duration of the study period&#xD;
Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Dose of Morphine Used</title>
          <description>The maximum dose of morphine in mg/kg used for symptom control</description>
          <units>mg/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" spread="0.05"/>
                    <measurement group_id="O2" value="0.10" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Daily Dose of Oral Morphine Over Hospital Stay</title>
        <description>The average daily dose of morphine used throughout study period in mg/kg/day</description>
        <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clonidine</title>
            <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period&#xD;
Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo solution will be given for the duration of the study period&#xD;
Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</description>
          </group>
        </group_list>
        <measure>
          <title>Average Daily Dose of Oral Morphine Over Hospital Stay</title>
          <description>The average daily dose of morphine used throughout study period in mg/kg/day</description>
          <units>mg/kg/day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="0.2"/>
                    <measurement group_id="O2" value="0.4" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of Episodes of Heart Rate Variability (Heart Beats/Min)</title>
        <description>Number of episodes of bradycardia (Heart rate &lt; 60/min for a minimum of 20 seconds and not associated with apnea or signs of reflux such as emesis, regurgitation of milk into the mouth or nose, arching while feeding, number of episodes of tachycardia (Heart rate &gt; 200/min) and not related to pain and/or agitation</description>
        <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clonidine</title>
            <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period&#xD;
Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo solution will be given for the duration of the study period&#xD;
Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Episodes of Heart Rate Variability (Heart Beats/Min)</title>
          <description>Number of episodes of bradycardia (Heart rate &lt; 60/min for a minimum of 20 seconds and not associated with apnea or signs of reflux such as emesis, regurgitation of milk into the mouth or nose, arching while feeding, number of episodes of tachycardia (Heart rate &gt; 200/min) and not related to pain and/or agitation</description>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <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>Total Number of Episodes of Blood Pressure (mm of Hg) Variability</title>
        <description>Number of episodes of hypotension (blood pressure &lt; 5th percentile for age) and hypertension (blood pressure &gt; 95th percentile for age)</description>
        <time_frame>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Clonidine</title>
            <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period&#xD;
Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo solution will be given for the duration of the study period&#xD;
Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Episodes of Blood Pressure (mm of Hg) Variability</title>
          <description>Number of episodes of hypotension (blood pressure &lt; 5th percentile for age) and hypertension (blood pressure &gt; 95th percentile for age)</description>
          <units>episodes</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <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>From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Clonidine</title>
          <description>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period&#xD;
Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo solution will be given for the duration of the study period&#xD;
Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </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="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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. Kunal Gupta</name_or_title>
      <organization>Hennepin County Medical Center</organization>
      <phone>6128732677</phone>
      <email>kunal.gupta@hcmed.org</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/NCT03762317
org study id: NAS
nct id: NCT03762317
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a prospective randomized double blinded study comparing the effect on duration of
      pharmacologic treatment and duration of hospital stay when using clonidine at 12
      µg/kilogram/day as an adjunct to oral morphine as compared to morphine monotherapy in the
      management of term and near term infants with neonatal abstinence syndrome (NAS)
Neonatal abstinence syndrome (NAS) is an emerging epidemic and has lead to a tremendous
      increase in cost of medical care. Opioids are the mainstay of treatment for NAS although
      there are concerns about possible short-term and long-term effects including but not limited
      to adverse neurodevelopmental outcomes. Other drugs such as clonidine, phenobarbitone,
      methadone and buprenorphine have been evaluated to limit the postnatal exposure to opioids in
      these infants. Clonidine is an alpha 2 receptor and can lessen withdrawal manifestations. The
      addition of clonidine at 6 µg/kilogram/day to morphine in the management of NAS has been
      shown to reduce the duration of pharmacotherapy by about 27% in a previous study.

      A recent pilot study reported reduction of treatment duration for NAS with clonidine (12
      µg/kilogram/day) monotherapy as compared to morphine monotherapy. The study reported no
      adverse effects in study subjects at the doses used in the study. The investigators
      hypothesize that there will be a minimum of 30% reduction in the treatment duration with 12
      µg/kilogram/day clonidine used as adjuncts to standard morphine treatment as compared to
      morphine monotherapy in the management of term and near term infants with NAS
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Duration of Pharmacotherapy for NAS
time frame: From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days
description: The length of time in days from the initiation of pharmacotherapy on day 1 until the medication has been stopped
measure: Duration of Hospital Stay
time frame: From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days
description: Number of days spent in the hospital
measure: Maximum Dose of Morphine Used
time frame: From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days
description: The maximum dose of morphine in mg/kg used for symptom control
measure: Average Daily Dose of Oral Morphine Over Hospital Stay
time frame: From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days
description: The average daily dose of morphine used throughout study period in mg/kg/day
measure: Total Number of Episodes of Heart Rate Variability (Heart Beats/Min)
time frame: From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days
description: Number of episodes of bradycardia (Heart rate < 60/min for a minimum of 20 seconds and not associated with apnea or signs of reflux such as emesis, regurgitation of milk into the mouth or nose, arching while feeding, number of episodes of tachycardia (Heart rate > 200/min) and not related to pain and/or agitation
measure: Total Number of Episodes of Blood Pressure (mm of Hg) Variability
time frame: From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days
description: Number of episodes of hypotension (blood pressure < 5th percentile for age) and hypertension (blood pressure > 95th percentile for age)
arm group label: clonidine
arm group type: Active Comparator
description: Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo solution will be given for the duration of the study period
intervention type: Drug
intervention name: Clonidine
description: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine
arm group label: clonidine
intervention type: Drug
intervention name: Placebo
description: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine
arm group label: Placebo
criteria: 
gender: All
minimum age: 36 Weeks
maximum age: 45 Weeks
healthy volunteers: No
last name: kunal gupta
role: Principal Investigator
affiliation: Hennepin County Medical Center, Minneapolis
last name: vinay sharma
role: Principal Investigator
affiliation: Hennepin County Medical Center, Minneapolis
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Hennepin County Medical Center, Minneapolis
investigator full name: kunal gupta
investigator title: Assistant Professor
mesh term: Neonatal Abstinence Syndrome
mesh term: Syndrome
mesh term: Clonidine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 