<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/NCT01734551</url>
  </required_header>
  <id_info>
    <org_study_id>11-0534</org_study_id>
    <nct_id>NCT01734551</nct_id>
  </id_info>
  <brief_title>NAS Treatment - Opiate Versus Non-Opiate</brief_title>
  <acronym>NAS</acronym>
  <official_title>Pharmacological Treatment of Neonatal Abstinence Syndrome: Opiate Versus Non-Opiate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Henrietta Bada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare two different medicines to treat babies with opiate&#xD;
      withdrawal. The treatment medicines are morphine, which is an opiate, and clonidine, a&#xD;
      non-opiate. Morphine is a narcotic medicine, with is included in most pain killers. Clonidine&#xD;
      is another drug, but is different from morphine. It is also used for babies, and even adults&#xD;
      for withdrawal symptoms. Both drugs are effective, but the purpose of this study is to see if&#xD;
      one may be better than the other.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Withdrawal from drugs, called Neonatal abstinence syndrome (NAS), is a group of symptoms that&#xD;
      occurs to babies whose mother took or used drugs (prescription, addicting, illegal, pain&#xD;
      pills, or drugs for addiction treatment) during pregnancy. Medicines the mother takes while&#xD;
      pregnant, the baby also takes. Babies may experience withdrawal after delivery, and may need&#xD;
      treatment. There are different ways to treat babies with withdrawal - about 50% of doctors&#xD;
      use morphine, an opiate, to treat these babies, the rest uses other drugs, like clonidine and&#xD;
      phenobarbitol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2011</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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>Finnegan Neonatal Abstinence Scoring System</measure>
    <time_frame>14 days</time_frame>
    <description>Mean of total Finnegan Scores obtained every 3 hours on days 2, 7, and 14 following start of treatment; A score is a number representing the total score or sum from 21 items or symptoms or manifestations of opiate withdrawal in newborn infants. The total score ranges from 0 to 43. Reference: 1. Finnegan LP, Connaughton JF, Jr., Kron RE, et al. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975;2(1-2):141-58. Although normal newborn may manifest mild symptoms that will give scores in the range of 0 to 7. A score of 8 consecutively obtained times 3 indicate that infant will benefit from treatment, in this study morphine or clonidine. A decrease in scores especially to less than 8 is suggestive of a good response to treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of Treatment</measure>
    <time_frame>120 days</time_frame>
    <description>Total number days of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)</measure>
    <time_frame>5-10 days after treatment starts</time_frame>
    <description>The summary scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) give a measure of infant neurobehavior in the following areas (score range): habituation (1-9), regulation (2.20-7.50), attention (1.29 -8.4), Handling (0 - 1), quality of movement (1.20 - 6.20), Non-optimal reflexes (0-12), Asymmetric reflexes (0-7), arousal (2.43 - 6.67), hypertonicity (0- 8), hypotonicity (0 - 5.0), excitability (0-11), lethargy (0 - 11.0). and stress/abstinence (0. - 0.57). A higher score for each item means a higher level of the construct. For example, a higher score for hypertonicity means the infant is more hypertonic and higher score on hypotonicity means the infant is more hypotonic. No cut-off score published for normal or abnormal behavioral performance. Reference: Lester BM et al. Summary Statistics of Neonatal Intensive Care Unit Network Neurobehavioral Scale Scores From the Maternal Lifestyle Study: A Quasinormative Sample, in Pediatrics 2004; 113,668.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bayley Scales of Infant and Toddler Development Third Edition</measure>
    <time_frame>1 year of life</time_frame>
    <description>Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15. Scores below 1 standard deviation (= or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain The score for each domain (motor, cognitive, and language functioning) represents the full-scale score</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Neonatal Abstinence Syndrome</condition>
  <arm_group>
    <arm_group_label>Morphine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clonidine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.&#xD;
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is &lt;0.1mg/kg/day, may discontinue.</description>
    <arm_group_label>Morphine</arm_group_label>
    <other_name>Morphine sulfate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clonidine</intervention_name>
    <description>Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.</description>
    <arm_group_label>Clonidine</arm_group_label>
    <other_name>clonidine hydrochloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Admitted to Neonatal Intensive Care Unit (NICU)- Gestational age (GA) &gt;or= 35 wks&#xD;
&#xD;
          -  Known prenatal opiate exposure (maternal history, positive opiate screen, positive&#xD;
             neonatal urine or meconium screen)&#xD;
&#xD;
          -  Symptomatic with Finnegan Neonatal Abstinence Scores meeting NICU protocol for&#xD;
             treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Seizures&#xD;
&#xD;
          -  Major congenital malformations&#xD;
&#xD;
          -  Unlikely to survive&#xD;
&#xD;
          -  Parents not able to understand English&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>7 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Henrietta S Bada, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky Medical Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>November 21, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <results_first_submitted>September 23, 2016</results_first_submitted>
  <results_first_submitted_qc>August 11, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">September 12, 2017</results_first_posted>
  <last_update_submitted>August 11, 2017</last_update_submitted>
  <last_update_submitted_qc>August 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Henrietta Bada</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>Prenatal opiate exposure</keyword>
  <keyword>neonatal withdrawal</keyword>
  <keyword>Pharmacologic treatment</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>Clonidine</mesh_term>
    <mesh_term>Morphine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Morphine</title>
          <description>Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.&#xD;
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is &lt;0.1mg/kg/day, may discontinue.</description>
        </group>
        <group group_id="P2">
          <title>Clonidine</title>
          <description>Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="16"/>
              </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>Morphine</title>
          <description>Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.&#xD;
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is &lt;0.1mg/kg/day, may discontinue.</description>
        </group>
        <group group_id="B2">
          <title>Clonidine</title>
          <description>Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.</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="15"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="31"/>
          </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="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="31"/>
                  </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>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="8"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </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="15"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Finnegan Neonatal Abstinence Scoring System</title>
        <description>Mean of total Finnegan Scores obtained every 3 hours on days 2, 7, and 14 following start of treatment; A score is a number representing the total score or sum from 21 items or symptoms or manifestations of opiate withdrawal in newborn infants. The total score ranges from 0 to 43. Reference: 1. Finnegan LP, Connaughton JF, Jr., Kron RE, et al. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975;2(1-2):141-58. Although normal newborn may manifest mild symptoms that will give scores in the range of 0 to 7. A score of 8 consecutively obtained times 3 indicate that infant will benefit from treatment, in this study morphine or clonidine. A decrease in scores especially to less than 8 is suggestive of a good response to treatment.</description>
        <time_frame>14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.&#xD;
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is &lt;0.1mg/kg/day, may discontinue.</description>
          </group>
          <group group_id="O2">
            <title>Clonidine</title>
            <description>Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.</description>
          </group>
        </group_list>
        <measure>
          <title>Finnegan Neonatal Abstinence Scoring System</title>
          <description>Mean of total Finnegan Scores obtained every 3 hours on days 2, 7, and 14 following start of treatment; A score is a number representing the total score or sum from 21 items or symptoms or manifestations of opiate withdrawal in newborn infants. The total score ranges from 0 to 43. Reference: 1. Finnegan LP, Connaughton JF, Jr., Kron RE, et al. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975;2(1-2):141-58. Although normal newborn may manifest mild symptoms that will give scores in the range of 0 to 7. A score of 8 consecutively obtained times 3 indicate that infant will benefit from treatment, in this study morphine or clonidine. A decrease in scores especially to less than 8 is suggestive of a good response to treatment.</description>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Finnegan scores day 2 of treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" spread="0.35"/>
                    <measurement group_id="O2" value="8.5" spread="0.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Finnegan scores day 7 of treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.6" spread="0.65"/>
                    <measurement group_id="O2" value="5.7" spread="0.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Finnegan scores day 14 of treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1" spread="1.1"/>
                    <measurement group_id="O2" value="6.7" spread="0.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Duration of Treatment</title>
        <description>Total number days of treatment</description>
        <time_frame>120 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.&#xD;
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is &lt;0.1mg/kg/day, may discontinue.</description>
          </group>
          <group group_id="O2">
            <title>Clonidine</title>
            <description>Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Treatment</title>
          <description>Total number days of treatment</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39" lower_limit="26" upper_limit="89"/>
                    <measurement group_id="O2" value="27" lower_limit="18" upper_limit="107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)</title>
        <description>The summary scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) give a measure of infant neurobehavior in the following areas (score range): habituation (1-9), regulation (2.20-7.50), attention (1.29 -8.4), Handling (0 - 1), quality of movement (1.20 - 6.20), Non-optimal reflexes (0-12), Asymmetric reflexes (0-7), arousal (2.43 - 6.67), hypertonicity (0- 8), hypotonicity (0 - 5.0), excitability (0-11), lethargy (0 - 11.0). and stress/abstinence (0. - 0.57). A higher score for each item means a higher level of the construct. For example, a higher score for hypertonicity means the infant is more hypertonic and higher score on hypotonicity means the infant is more hypotonic. No cut-off score published for normal or abnormal behavioral performance. Reference: Lester BM et al. Summary Statistics of Neonatal Intensive Care Unit Network Neurobehavioral Scale Scores From the Maternal Lifestyle Study: A Quasinormative Sample, in Pediatrics 2004; 113,668.</description>
        <time_frame>5-10 days after treatment starts</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.&#xD;
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is &lt;0.1mg/kg/day, may discontinue.</description>
          </group>
          <group group_id="O2">
            <title>Clonidine</title>
            <description>Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.</description>
          </group>
        </group_list>
        <measure>
          <title>Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)</title>
          <description>The summary scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) give a measure of infant neurobehavior in the following areas (score range): habituation (1-9), regulation (2.20-7.50), attention (1.29 -8.4), Handling (0 - 1), quality of movement (1.20 - 6.20), Non-optimal reflexes (0-12), Asymmetric reflexes (0-7), arousal (2.43 - 6.67), hypertonicity (0- 8), hypotonicity (0 - 5.0), excitability (0-11), lethargy (0 - 11.0). and stress/abstinence (0. - 0.57). A higher score for each item means a higher level of the construct. For example, a higher score for hypertonicity means the infant is more hypertonic and higher score on hypotonicity means the infant is more hypotonic. No cut-off score published for normal or abnormal behavioral performance. Reference: Lester BM et al. Summary Statistics of Neonatal Intensive Care Unit Network Neurobehavioral Scale Scores From the Maternal Lifestyle Study: A Quasinormative Sample, in Pediatrics 2004; 113,668.</description>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Attention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.06" spread="0.27"/>
                    <measurement group_id="O2" value="4.51" spread="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Handling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.36" spread="0.06"/>
                    <measurement group_id="O2" value="0.42" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quality of movement</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.77" spread="0.15"/>
                    <measurement group_id="O2" value="4.92" spread="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Regulation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" spread="0.18"/>
                    <measurement group_id="O2" value="5.26" spread="0.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-optimal reflexes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.73" spread="0.42"/>
                    <measurement group_id="O2" value="4.13" spread="0.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asymmetric reflexes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20" spread="0.14"/>
                    <measurement group_id="O2" value="0.00" spread="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stress/abstinence</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07" spread="0.01"/>
                    <measurement group_id="O2" value="0.08" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Arousal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.91" spread="0.13"/>
                    <measurement group_id="O2" value="3.95" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypertonicity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.40" spread="0.25"/>
                    <measurement group_id="O2" value="0.25" spread="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypotonicity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.13" spread="0.13"/>
                    <measurement group_id="O2" value="0.19" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Excitability</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="0.53"/>
                    <measurement group_id="O2" value="2.38" spread="0.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lethargy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" spread="0.50"/>
                    <measurement group_id="O2" value="5.13" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bayley Scales of Infant and Toddler Development Third Edition</title>
        <description>Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15. Scores below 1 standard deviation (= or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain The score for each domain (motor, cognitive, and language functioning) represents the full-scale score</description>
        <time_frame>1 year of life</time_frame>
        <population>The above number fo reach arm represents the number of subjects who came for follow-up evaluation.</population>
        <group_list>
          <group group_id="O1">
            <title>Morphine</title>
            <description>Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.&#xD;
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is &lt;0.1mg/kg/day, may discontinue.</description>
          </group>
          <group group_id="O2">
            <title>Clonidine</title>
            <description>Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.</description>
          </group>
        </group_list>
        <measure>
          <title>Bayley Scales of Infant and Toddler Development Third Edition</title>
          <description>Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15. Scores below 1 standard deviation (= or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain The score for each domain (motor, cognitive, and language functioning) represents the full-scale score</description>
          <population>The above number fo reach arm represents the number of subjects who came for follow-up evaluation.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Bayley III motor</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.6" spread="10.4"/>
                    <measurement group_id="O2" value="95.8" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cognitive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.9" spread="8.4"/>
                    <measurement group_id="O2" value="93.3" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Language total</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.0" spread="13.8"/>
                    <measurement group_id="O2" value="95.8" spread="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Language Receptive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101.1" spread="14.3"/>
                    <measurement group_id="O2" value="95.0" spread="12.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Language Expressive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" spread="13.1"/>
                    <measurement group_id="O2" value="99.2" spread="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <desc>Daily review of inpatient care and activity. Upon discharge, electronic medical records reviewed for 3 months after infant left UK NICU. Assessments at NICU Graduate Clinic were done at 3 months</desc>
      <group_list>
        <group group_id="E1">
          <title>Morphine</title>
          <description>Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Morphine: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.&#xD;
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is &lt;0.1mg/kg/day, may discontinue.</description>
        </group>
        <group group_id="E2">
          <title>Clonidine</title>
          <description>Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.&#xD;
Clonidine: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.</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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </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. Henrietta S. Bada, Professor and Vice Chair, Academic Affairs</name_or_title>
      <organization>University of Kentucky</organization>
      <phone>859-323-1019</phone>
      <email>hbada2@uky.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01734551
org study id: 11-0534
nct id: NCT01734551
lead sponsor: 
has dmc: Yes
The purpose of this study is to compare two different medicines to treat babies with opiate
      withdrawal. The treatment medicines are morphine, which is an opiate, and clonidine, a
      non-opiate. Morphine is a narcotic medicine, with is included in most pain killers. Clonidine
      is another drug, but is different from morphine. It is also used for babies, and even adults
      for withdrawal symptoms. Both drugs are effective, but the purpose of this study is to see if
      one may be better than the other.
Withdrawal from drugs, called Neonatal abstinence syndrome (NAS), is a group of symptoms that
      occurs to babies whose mother took or used drugs (prescription, addicting, illegal, pain
      pills, or drugs for addiction treatment) during pregnancy. Medicines the mother takes while
      pregnant, the baby also takes. Babies may experience withdrawal after delivery, and may need
      treatment. There are different ways to treat babies with withdrawal - about 50% of doctors
      use morphine, an opiate, to treat these babies, the rest uses other drugs, like clonidine and
      phenobarbitol.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Finnegan Neonatal Abstinence Scoring System
time frame: 14 days
description: Mean of total Finnegan Scores obtained every 3 hours on days 2, 7, and 14 following start of treatment; A score is a number representing the total score or sum from 21 items or symptoms or manifestations of opiate withdrawal in newborn infants. The total score ranges from 0 to 43. Reference: 1. Finnegan LP, Connaughton JF, Jr., Kron RE, et al. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975;2(1-2):141-58. Although normal newborn may manifest mild symptoms that will give scores in the range of 0 to 7. A score of 8 consecutively obtained times 3 indicate that infant will benefit from treatment, in this study morphine or clonidine. A decrease in scores especially to less than 8 is suggestive of a good response to treatment.
measure: Duration of Treatment
time frame: 120 days
description: Total number days of treatment
measure: Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
time frame: 5-10 days after treatment starts
description: The summary scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) give a measure of infant neurobehavior in the following areas (score range): habituation (1-9), regulation (2.20-7.50), attention (1.29 -8.4), Handling (0 - 1), quality of movement (1.20 - 6.20), Non-optimal reflexes (0-12), Asymmetric reflexes (0-7), arousal (2.43 - 6.67), hypertonicity (0- 8), hypotonicity (0 - 5.0), excitability (0-11), lethargy (0 - 11.0). and stress/abstinence (0. - 0.57). A higher score for each item means a higher level of the construct. For example, a higher score for hypertonicity means the infant is more hypertonic and higher score on hypotonicity means the infant is more hypotonic. No cut-off score published for normal or abnormal behavioral performance. Reference: Lester BM et al. Summary Statistics of Neonatal Intensive Care Unit Network Neurobehavioral Scale Scores From the Maternal Lifestyle Study: A Quasinormative Sample, in Pediatrics 2004; 113,668.
measure: Bayley Scales of Infant and Toddler Development Third Edition
time frame: 1 year of life
description: Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15. Scores below 1 standard deviation (= or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain The score for each domain (motor, cognitive, and language functioning) represents the full-scale score
arm group label: Morphine
arm group type: Active Comparator
description: Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.
arm group label: Clonidine
arm group type: Active Comparator
description: Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months.
intervention type: Drug
intervention name: Morphine
description: Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day.
Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is <0.1mg/kg/day, may discontinue.
arm group label: Morphine
other name: Morphine sulfate
intervention type: Drug
intervention name: Clonidine
description: Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.
arm group label: Clonidine
other name: clonidine hydrochloride
criteria: 
gender: All
minimum age: 1 Day
maximum age: 7 Days
healthy volunteers: No
last name: Henrietta S Bada, MD
role: Principal Investigator
affiliation: University of Kentucky
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Henrietta Bada
investigator title: PI
mesh term: Neonatal Abstinence Syndrome
mesh term: Syndrome
mesh term: Clonidine
mesh term: Morphine
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 