<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/NCT01708707</url>
  </required_header>
  <id_info>
    <org_study_id>Banner IRB 01-13-0030</org_study_id>
    <nct_id>NCT01708707</nct_id>
  </id_info>
  <brief_title>Comparison of Buprenorphine to Morphine in Treatment of Neonatal Abstinence Syndrome (NAS)</brief_title>
  <official_title>A Randomized Comparison of Sublingual Buprenorphine to Morphine Sulfate in the Treatment of Neonatal Abstinence Syndrome (NAS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pediatrix</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pediatrix</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine whether buprenorphine is a beneficial, safe, cost&#xD;
      effective treatment alternative to morphine sulfate in the treatment of Neonatal Abstinence&#xD;
      Syndrome (NAS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neonatal abstinence syndrome is a condition that affects newborns who are exposed to chronic&#xD;
      opioid drugs while they are in a mother's uterus (womb) prior to birth. The current standard&#xD;
      of care treatment includes morphine sulfate. Buprenorphine is a drug used in adults to treat&#xD;
      narcotic dependence and withdrawal, but has not yet been approved for use in newborns as a&#xD;
      treatment alternative for Neonatal Abstinence Syndrome. This investigation is designed to&#xD;
      measure if sublingual (under the tongue) buprenorphine is able to reduce hospital length of&#xD;
      stay and decrease number of days of drug treatment currently required in treatment of NAS.&#xD;
      Another goal will be to understand buprenorphine as a cost effective treatment for NAS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">October 31, 2017</completion_date>
  <primary_completion_date type="Actual">October 2017</primary_completion_date>
  <phase>Phase 2</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>Hospital length of stay</measure>
    <time_frame>Up to hospital discharge, an anticipated average of 4 weeks</time_frame>
    <description>Number of days of hospital admission</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of adverse or serious adverse events</measure>
    <time_frame>Up to hospital discharge, with length of stay currently averaging approximately 4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost efficiency of buprenorphine</measure>
    <time_frame>At least 48 prior to hospital discharge, with anticipated discharge averaging to be 4 weeks</time_frame>
    <description>Cost of buprenorphine as a product of number of days of administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Withdrawal symptoms</measure>
    <time_frame>Up to hospital discharge, usually occuring on average 4 weeks</time_frame>
    <description>Finnegan methodology to score withdrawal symptoms every four hours of medication administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue dosage administration</measure>
    <time_frame>Up to hospital discharge, anticipating an average of 4 weeks</time_frame>
    <description>Number of rescue doses of additional medication</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Neonatal Abstinence Syndrome</condition>
  <condition>Neonatal Withdrawal Syndrome</condition>
  <arm_group>
    <arm_group_label>Oral morphine sulfate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral morphine sulfate 0.4 mg/kg/day morphine every 3-4 hours as needed for Finnegan scores suggestive of Neonatal Abstinence Syndrome Other Name: morphine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Buprenorphine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sublingual Buprenorphine 15.9 µg/kg per day in 3 divided doses, titrated up or escalated down based upon standardized scoring for neonatal abstinence syndrome</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buprenorphine</intervention_name>
    <description>The injectable formulation of buprenorphine (Buprenex; Reckitt Benckiser) will be prepared to a final concentration of 0.075 mg/mL in 100% ethanol and simple syrup USP to create a sublingual preparation.&#xD;
Infants initial dose: 15.9 µg/kg per day in 3 divided doses with escalation/weaning based upon standardized scoring of NAS symptoms, using standardized Finnegan scoring Maximum dosage: 60 µg/kg per day Duration: Infants will receive buprenorphine until they are successfully weaned off of opioids and no longer show withdrawal symptoms, evidenced by low Finnegan scores. Mean use in other investigations was 24 days.</description>
    <arm_group_label>Buprenorphine</arm_group_label>
    <other_name>Sublingual buprenorphine</other_name>
    <other_name>Other Name: Buprenex (buprenorphine)</other_name>
    <other_name>NDC Number: 12496-0757-1</other_name>
    <other_name>Product Code: 12496-0757</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine Sulfate</intervention_name>
    <description>Oral Morphine Sulfate Dosage: Morphine Sulfate Oral Solution 100mg/5mL Initially dosed at 0.4mg/kg per day in six daily doses Duration of medication administration dependent upon infant symptoms of neonatal withdrawal, with mean duration of use at Banner Good Samaritan Hospital currently averaging 25 days.</description>
    <arm_group_label>Oral morphine sulfate</arm_group_label>
    <other_name>Oral Morphine Sulfate</other_name>
    <other_name>Morphine</other_name>
    <other_name>NDC: 0406-8003-24</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infants of corrected gestational age ≥37 weeks&#xD;
&#xD;
          -  Chronic opioid exposure in utero&#xD;
&#xD;
          -  Signs and symptoms of NAS requiring treatment&#xD;
&#xD;
          -  2 consecutive Finnegan scores ≥8 or any single score ≥12&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant maternal benzodiazepine or alcohol use 30 days prior to enrollment&#xD;
&#xD;
          -  Life-threatening congenital malformations&#xD;
&#xD;
          -  Intrauterine growth retardation&#xD;
&#xD;
          -  Seizure activity or congenital neurologic abnormalities&#xD;
&#xD;
          -  Concomitant neonatal use of Cytochrome P450 inhibitor or inducers prior to treatment&#xD;
&#xD;
          -  Inability of mother's consent due to altered mental status or comorbid psychiatric&#xD;
             disorder&#xD;
&#xD;
          -  Neonatal administration of morphine prior to enrollment into study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>1 Year</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gregory Martin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Banner University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner - University Medical Center Phoenix</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>April 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 17, 2012</study_first_posted>
  <last_update_submitted>August 14, 2018</last_update_submitted>
  <last_update_submitted_qc>August 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>
    <mesh_term>Substance Withdrawal 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/NCT01708707
org study id: Banner IRB 01-13-0030
nct id: NCT01708707
lead sponsor: 
has dmc: Yes
The purpose of the study is to determine whether buprenorphine is a beneficial, safe, cost
      effective treatment alternative to morphine sulfate in the treatment of Neonatal Abstinence
      Syndrome (NAS).
Neonatal abstinence syndrome is a condition that affects newborns who are exposed to chronic
      opioid drugs while they are in a mother's uterus (womb) prior to birth. The current standard
      of care treatment includes morphine sulfate. Buprenorphine is a drug used in adults to treat
      narcotic dependence and withdrawal, but has not yet been approved for use in newborns as a
      treatment alternative for Neonatal Abstinence Syndrome. This investigation is designed to
      measure if sublingual (under the tongue) buprenorphine is able to reduce hospital length of
      stay and decrease number of days of drug treatment currently required in treatment of NAS.
      Another goal will be to understand buprenorphine as a cost effective treatment for NAS.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Hospital length of stay
time frame: Up to hospital discharge, an anticipated average of 4 weeks
description: Number of days of hospital admission
measure: Number of adverse or serious adverse events
time frame: Up to hospital discharge, with length of stay currently averaging approximately 4 weeks
measure: Cost efficiency of buprenorphine
time frame: At least 48 prior to hospital discharge, with anticipated discharge averaging to be 4 weeks
description: Cost of buprenorphine as a product of number of days of administration
measure: Withdrawal symptoms
time frame: Up to hospital discharge, usually occuring on average 4 weeks
description: Finnegan methodology to score withdrawal symptoms every four hours of medication administration
measure: Rescue dosage administration
time frame: Up to hospital discharge, anticipating an average of 4 weeks
description: Number of rescue doses of additional medication
arm group label: Oral morphine sulfate
arm group type: Active Comparator
description: Oral morphine sulfate 0.4 mg/kg/day morphine every 3-4 hours as needed for Finnegan scores suggestive of Neonatal Abstinence Syndrome Other Name: morphine
arm group label: Buprenorphine
arm group type: Experimental
description: Sublingual Buprenorphine 15.9 µg/kg per day in 3 divided doses, titrated up or escalated down based upon standardized scoring for neonatal abstinence syndrome
intervention type: Drug
intervention name: Buprenorphine
description: The injectable formulation of buprenorphine (Buprenex; Reckitt Benckiser) will be prepared to a final concentration of 0.075 mg/mL in 100% ethanol and simple syrup USP to create a sublingual preparation.
Infants initial dose: 15.9 µg/kg per day in 3 divided doses with escalation/weaning based upon standardized scoring of NAS symptoms, using standardized Finnegan scoring Maximum dosage: 60 µg/kg per day Duration: Infants will receive buprenorphine until they are successfully weaned off of opioids and no longer show withdrawal symptoms, evidenced by low Finnegan scores. Mean use in other investigations was 24 days.
arm group label: Buprenorphine
other name: Sublingual buprenorphine
other name: Other Name: Buprenex (buprenorphine)
other name: NDC Number: 12496-0757-1
other name: Product Code: 12496-0757
intervention type: Drug
intervention name: Morphine Sulfate
description: Oral Morphine Sulfate Dosage: Morphine Sulfate Oral Solution 100mg/5mL Initially dosed at 0.4mg/kg per day in six daily doses Duration of medication administration dependent upon infant symptoms of neonatal withdrawal, with mean duration of use at Banner Good Samaritan Hospital currently averaging 25 days.
arm group label: Oral morphine sulfate
other name: Oral Morphine Sulfate
other name: Morphine
other name: NDC: 0406-8003-24
criteria: 
gender: All
minimum age: N/A
maximum age: 1 Year
healthy volunteers: No
last name: Gregory Martin, MD
role: Principal Investigator
affiliation: Banner University Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neonatal Abstinence Syndrome
mesh term: Syndrome
mesh term: Substance Withdrawal Syndrome
mesh term: Morphine
mesh term: Buprenorphine