<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/NCT01671410</url>
  </required_header>
  <id_info>
    <org_study_id>12D.398</org_study_id>
    <nct_id>NCT01671410</nct_id>
  </id_info>
  <brief_title>Buprenorphine for Treatment of Neonatal Abstinence Syndrome in Infants With In Utero Exposure to Benzodiazepines</brief_title>
  <acronym>MOPPlus</acronym>
  <official_title>A Randomized, Open Label Clinical Trial of Buprenorphine in the Treatment of Neonatal Abstinence Syndrome in Infants With In Utero Exposure to Benzodiazepines or Are Breastfeeding</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Thomas Jefferson University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The opioid neonatal abstinence syndrome (NAS) is a condition of withdrawal symptoms after&#xD;
      utero exposure to opioids. Sublingual buprenorphine shows promise as a new treatment in NAS.&#xD;
      This trial will investigate the safety and tolerability of sublingual buprenorphine in&#xD;
      infants exposed to both opioids and benzodiazepines in utero or with exposure of opioids in&#xD;
      those who are breastfeeding.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Infants with in utero exposure to opioids often require therapy with morphine for an extended&#xD;
      period. In a clinical trial, sublingual buprenorphine reduced this treatment period by ~30%.&#xD;
      However, infants with both opioid and benzodiazepine exposure were not included in the trial.&#xD;
      This study will test the safety and tolerability of sublingual buprenorphine in infants with&#xD;
      in utero exposure to benzodiazepines or who are breastfeeding.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>Phase 1</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>Length of treatment</measure>
    <time_frame>Patients will be followed for the duration of hospital stay, an expected average of 5 weeks</time_frame>
    <description>This endpoint will compare length of treatment (in days) using sublingual buprenorphine or oral morphine solution.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of hospitalization</measure>
    <time_frame>Patients will be followed for the duration of hospital stay, an expected average of 5 weeks</time_frame>
    <description>This endpoint will compare length of stay (in days) using sublingual buprenorphine or oral morphine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients requiring supplemental phenobarbital treatment</measure>
    <time_frame>Patients will be followed for the duration of hospital stay, an expected average of 5 weeks</time_frame>
    <description>This endpoint will compare requirement number of patients who require use of supplemental phenobarbital for treatment of NAS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events as a measure of safety and tolerability</measure>
    <time_frame>Patients will be followed for the duration of hospital stay, an expected average of 5 weeks</time_frame>
    <description>Adverse events will be collected, graded by severity, and assessed for causality referent to study drug.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Feeding patterns</measure>
    <time_frame>Patients will be followed for the duration of hospital stay, an expected average of 5 weeks</time_frame>
    <description>To compare the feeding patterns, weight gain, and incidence of feeding dysfunction in infants treated with sublingual buprenorphine and oral morphine for NAS</description>
  </other_outcome>
  <other_outcome>
    <measure>Respiratory Patterns</measure>
    <time_frame>Patients will be followed for the duration of hospital stay, an expected average of 5 weeks</time_frame>
    <description>To compare the respiratory patterns of infants receiving sublingual buprenorphine or morphine solution for the pharmacologic treatment of NAS after in utero exposure to opioids and benzodiazepines and/or postnatal breast milk.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Neonatal Abstinence Syndrome</condition>
  <arm_group>
    <arm_group_label>sublingual buprenorphine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Initial daily dose: 15.9 mcg/kg/day; Initial unit dose: 5.3 mcg/kg q8 hours; Maximum daily dose: 60 mcg/kg/day; Up-titration rate: 25%; Weaning rate: 10%; Cessation Dose: Within 10 or 20% of starting dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>oral morphine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Initial daily dose: 0.4 mg/kg/day; Initial unit dose: 0.07 mg/kg q 4 hours; Maximum daily dose: 1.25 mg/kg/day; Up-titration rate: 20%; Weaning rate: 10%; Cessation Dose: 0.025 mg/kg q 4 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oral morphine</intervention_name>
    <description>Oral morphine for the treatment of neonatal abstinence syndrome</description>
    <arm_group_label>oral morphine</arm_group_label>
    <other_name>morphine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sublingual buprenorphine</intervention_name>
    <description>Sublingual buprenorphine for the treatment of neonatal abstinence syndrome</description>
    <arm_group_label>sublingual buprenorphine</arm_group_label>
    <other_name>buprenex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ≥ 37 weeks gestation&#xD;
&#xD;
          2. Exposure to opioids in utero&#xD;
&#xD;
          3. Demonstration of signs and symptoms of neonatal abstinence syndrome requiring&#xD;
             treatment&#xD;
&#xD;
          4. Exposure to benzodiazepines in utero and/or receiving breast milk. Benzodiazepine use&#xD;
             is defined as maternal use in the past 30 days, and/or receipt of benzodiazepines by&#xD;
             prescription (as determined by self-report or intake urine) by the mother 30 days&#xD;
             prior to birth.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Major congenital malformations and/or intrauterine growth retardation defined as birth&#xD;
             weight &lt;2200 gm&#xD;
&#xD;
          2. Medical illness requiring intensification of medical therapy. This includes, but is&#xD;
             not limited to suspected sepsis requiring antibiotic therapy.&#xD;
&#xD;
          3. Hypoglycemia requiring treatment with intravenous dextrose&#xD;
&#xD;
          4. Bilirubin &gt;20 mg/dL (The need for phototherapy is not exclusionary)&#xD;
&#xD;
          5. Seizure activity or other neurologic abnormality&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Walter K Kraft, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Thomas Jefferson University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>August 20, 2012</study_first_submitted>
  <study_first_submitted_qc>August 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 23, 2012</study_first_posted>
  <last_update_submitted>October 13, 2016</last_update_submitted>
  <last_update_submitted_qc>October 13, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neonatal Abstinence Syndrome</keyword>
  <keyword>buprenorphine</keyword>
  <keyword>morphine</keyword>
  <keyword>benzodiazepine</keyword>
  <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>Morphine</mesh_term>
    <mesh_term>Buprenorphine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01671410
org study id: 12D.398
nct id: NCT01671410
lead sponsor: 
has dmc: Yes
The opioid neonatal abstinence syndrome (NAS) is a condition of withdrawal symptoms after
      utero exposure to opioids. Sublingual buprenorphine shows promise as a new treatment in NAS.
      This trial will investigate the safety and tolerability of sublingual buprenorphine in
      infants exposed to both opioids and benzodiazepines in utero or with exposure of opioids in
      those who are breastfeeding.
Infants with in utero exposure to opioids often require therapy with morphine for an extended
      period. In a clinical trial, sublingual buprenorphine reduced this treatment period by ~30%.
      However, infants with both opioid and benzodiazepine exposure were not included in the trial.
      This study will test the safety and tolerability of sublingual buprenorphine in infants with
      in utero exposure to benzodiazepines or who are breastfeeding.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Length of treatment
time frame: Patients will be followed for the duration of hospital stay, an expected average of 5 weeks
description: This endpoint will compare length of treatment (in days) using sublingual buprenorphine or oral morphine solution.
measure: Length of hospitalization
time frame: Patients will be followed for the duration of hospital stay, an expected average of 5 weeks
description: This endpoint will compare length of stay (in days) using sublingual buprenorphine or oral morphine
measure: Number of patients requiring supplemental phenobarbital treatment
time frame: Patients will be followed for the duration of hospital stay, an expected average of 5 weeks
description: This endpoint will compare requirement number of patients who require use of supplemental phenobarbital for treatment of NAS
measure: Number of participants with adverse events as a measure of safety and tolerability
time frame: Patients will be followed for the duration of hospital stay, an expected average of 5 weeks
description: Adverse events will be collected, graded by severity, and assessed for causality referent to study drug.
measure: Feeding patterns
time frame: Patients will be followed for the duration of hospital stay, an expected average of 5 weeks
description: To compare the feeding patterns, weight gain, and incidence of feeding dysfunction in infants treated with sublingual buprenorphine and oral morphine for NAS
measure: Respiratory Patterns
time frame: Patients will be followed for the duration of hospital stay, an expected average of 5 weeks
description: To compare the respiratory patterns of infants receiving sublingual buprenorphine or morphine solution for the pharmacologic treatment of NAS after in utero exposure to opioids and benzodiazepines and/or postnatal breast milk.
arm group label: sublingual buprenorphine
arm group type: Experimental
description: Initial daily dose: 15.9 mcg/kg/day; Initial unit dose: 5.3 mcg/kg q8 hours; Maximum daily dose: 60 mcg/kg/day; Up-titration rate: 25%; Weaning rate: 10%; Cessation Dose: Within 10 or 20% of starting dose
arm group label: oral morphine
arm group type: Active Comparator
description: Initial daily dose: 0.4 mg/kg/day; Initial unit dose: 0.07 mg/kg q 4 hours; Maximum daily dose: 1.25 mg/kg/day; Up-titration rate: 20%; Weaning rate: 10%; Cessation Dose: 0.025 mg/kg q 4 hours
intervention type: Drug
intervention name: oral morphine
description: Oral morphine for the treatment of neonatal abstinence syndrome
arm group label: oral morphine
other name: morphine
intervention type: Drug
intervention name: sublingual buprenorphine
description: Sublingual buprenorphine for the treatment of neonatal abstinence syndrome
arm group label: sublingual buprenorphine
other name: buprenex
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Walter K Kraft, MD
role: Principal Investigator
affiliation: Thomas Jefferson University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neonatal Abstinence Syndrome
mesh term: Syndrome
mesh term: Morphine
mesh term: Buprenorphine