<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/NCT01720667</url>
  </required_header>
  <id_info>
    <org_study_id>NoGA - R01 FD004147-01A1 Haas</org_study_id>
    <secondary_id>1R01FD004147-01A1</secondary_id>
    <nct_id>NCT01720667</nct_id>
  </id_info>
  <brief_title>Efficacy of Intravenous Levetiracetam in Neonatal Seizures</brief_title>
  <acronym>NEOLEV2</acronym>
  <official_title>Efficacy of Intravenous Levetiracetam in Neonatal Seizures: A Phase 2 Randomized Blinded Controlled Study of the Efficacy of Intravenous Levetiracetam (LEV) as First Line Treatment for Neonatal Seizures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Richard H. Haas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rady Children's Hospital, San Diego</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Auckland City Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sharp Mary Birch Hospital for Women &amp; Newborns</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>UCSF Benioff Children's Hospital Oakland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Food and Drug Administration (FDA)</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Diego</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A new anticonvulsant, levetiracetam will be studied to treat seizures in newborn infants.&#xD;
      Current treatments for the brain damaging complication of neonatal seizures are&#xD;
      unsatisfactory.&#xD;
&#xD;
      Monitoring for seizure detection will be tested at five (5) US sites and one (1)&#xD;
      international site using the internet.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This project aims to improve the treatment of neonatal seizures. Current treatments are&#xD;
      poorly effective and have significant side effects.&#xD;
&#xD;
      Levetiracetam (LEV) has great potential as a treatment for neonatal seizures but is not&#xD;
      approved for use in children less than 2 years of age.&#xD;
&#xD;
      This study aims to obtain essential data regarding the efficacy and safety of LEV in this&#xD;
      vulnerable and under researched population and simultaneously to develop EEG monitoring&#xD;
      systems that facilitate seizure detection and research.&#xD;
&#xD;
      Specific aims are:&#xD;
&#xD;
        1. To determine the efficacy of intravenous LEV in terminating neonatal seizures when given&#xD;
           as first line therapy.&#xD;
&#xD;
        2. To obtain dose escalation data by studying the additional efficacy of a further dose in&#xD;
           non responders.&#xD;
&#xD;
        3. To obtain additional pharmacokinetic data to confirm findings from our previous&#xD;
           pharmacokinetic study.&#xD;
&#xD;
        4. To obtain further safety data of LEV in neonates.&#xD;
&#xD;
        5. To prove the feasibility of centralized remote monitoring of continuous EEG monitoring&#xD;
           in the Neonatal Intensive Care Unit (NICU) via the internet and test a promising&#xD;
           automated neonatal seizure detection algorithm.&#xD;
&#xD;
      The study design is a phase 2b randomized blinded controlled study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2013</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">October 31, 2017</primary_completion_date>
  <phase>Phase 1/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>Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg)</measure>
    <time_frame>24 hours</time_frame>
    <description>A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.&#xD;
Seizure cessation from 15 minutes after completion of infusion for 24 hours as assessed by continuous EEG reviewed by neurophysiologists.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment</measure>
    <time_frame>48 hours</time_frame>
    <description>A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Neonates With Seizure Termination at 1 Hour After Treatment</measure>
    <time_frame>1 hour</time_frame>
    <description>A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LEV Dose Escalation Component</measure>
    <time_frame>24 hours</time_frame>
    <description>Number of babies with seizure control at levetiracetam (60 mg/Kg load) who had not responded to 40 mg/kg load and number of babies with seizure control at 40 mg/kg who had not responded to 20 mg/kg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital Within the Hypoxic Ischemic Encephalopathy (HIE) Population and Treated With Hypothermia</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Pharmacokinetic Data</measure>
    <time_frame>48 hours</time_frame>
    <description>To obtain additional pharmacokinetic data &quot;Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax)&quot; of intravenous levetiracetam to confirm findings from our previous pharmacokinetic study.</description>
  </other_outcome>
  <other_outcome>
    <measure>Feasibility of Continuous Internet EEG Monitoring</measure>
    <time_frame>Subject study duration</time_frame>
    <description>Feasibility of centralized remote access to continuous video EEG monitoring in the NICU via the internet</description>
  </other_outcome>
  <other_outcome>
    <measure>Evaluation of the Accuracy of Neonatal Seizure Detection Algorithm</measure>
    <time_frame>48 Hours</time_frame>
    <description>A novel neonatal seizure detection algorithm will be compared to the gold standard of two encephalographers reading 48 hours of neonatal video EEG in the measurement of seizure burden.</description>
  </other_outcome>
  <other_outcome>
    <measure>Gather Safety Information on IV Levetiracetam</measure>
    <time_frame>5 days</time_frame>
    <description>Safety information to be collected includes daily recording of any adverse events during the 5 day treatment protocol.&#xD;
Complete Blood Count and Comprehensive Chemistry panels after 48 hours of treatment collected.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">280</enrollment>
  <condition>Neonatal Seizures</condition>
  <arm_group>
    <arm_group_label>Intravenous levetiracetam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intravenous phenobarbital</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous levetiracetam</intervention_name>
    <description>Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure.</description>
    <arm_group_label>Intravenous levetiracetam</arm_group_label>
    <other_name>Keppra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous phenobarbital</intervention_name>
    <description>Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load.</description>
    <arm_group_label>Intravenous phenobarbital</arm_group_label>
    <other_name>phenobarbitone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Newborns admitted to any of the study sites with electrographic seizures seizures.&#xD;
&#xD;
          2. Term infants gestational age &gt;36 weeks less than 2 weeks of age.&#xD;
&#xD;
          3. Greater than 2200 grams.&#xD;
&#xD;
          4. Infants for whom parental consent to participate in the study is obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Infants who are already receiving anticonvulsants&#xD;
&#xD;
          2. If serum creatinine is greater than 1.6mM&#xD;
&#xD;
          3. If seizures are due to correctable metabolic abnormalities (i.e. hypoglycaemia,&#xD;
             hypocalcemia, hyponatremia)&#xD;
&#xD;
          4. Subjects in whom death seems imminent, as assessed by the neonatologist.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Minutes</minimum_age>
    <maximum_age>14 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard H Haas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Diego</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU)</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012 Jul;72(1):43-9. doi: 10.1038/pr.2012.51. Epub 2012 Apr 11.</citation>
    <PMID>22495532</PMID>
  </reference>
  <results_reference>
    <citation>Sharpe C, Davis SL, Reiner GE, Lee LI, Gold JJ, Nespeca M, Wang SG, Joe P, Kuperman R, Gardner M, Honold J, Lane B, Knodel E, Rowe D, Battin MR, Bridge R, Goodmar J, Castro B, Rasmussen M, Arnell K, Harbert M, Haas R. Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected With Continuous Long-Term Neonatal Electroencephalography Monitoring. J Clin Neurophysiol. 2019 Jan;36(1):9-13. doi: 10.1097/WNP.0000000000000525.</citation>
    <PMID>30289769</PMID>
  </results_reference>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <results_first_submitted>July 3, 2019</results_first_submitted>
  <results_first_submitted_qc>August 12, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 21, 2019</results_first_posted>
  <last_update_submitted>August 12, 2019</last_update_submitted>
  <last_update_submitted_qc>August 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Richard H. Haas</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Seizures</keyword>
  <keyword>Neonates</keyword>
  <keyword>Anticonvulsants</keyword>
  <keyword>Treatment</keyword>
  <keyword>Levetiracetam</keyword>
  <keyword>Phenobarbital</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Seizures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levetiracetam</mesh_term>
    <mesh_term>Phenobarbital</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT01720667/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 13, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT01720667/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>280 were enrolled to EEG monitoring and of these 106 were randomized to treatment as neonatal seizures were thought to have occurred. 174 excluded as they did not have electrographic seizures; from 6 participants only verbal not written consent obtained.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Intravenous Levetiracetam</title>
          <description>Intravenous levetiracetam 40 - 60 mg/kg loading dose. If electrographic seizures persisted or recurred 15 minutes following completion of the infusion, subjects received a further 20 mg/kg LEV infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes following completion of the second infusion, the subject was then treated with PHB 20 mg/kg. Another dose of 20 mg/kg PHB given if seizures persist. Unresponsive subjects exit the study. All subjects received maintenance LEV 10 mg/kg/dose given IV q8 hours continued for five days.</description>
        </group>
        <group group_id="P2">
          <title>Intravenous Phenobarbital</title>
          <description>Intravenous phenobarbital 20 mg/kg loading dose. If electrographic seizures persisted or recurred 15 minutes following completion of the infusion, subjects received a further 20 mg/kg PHB infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes following completion of the second infusion, the subject was then treated with LEV 40 mg/kg first. Another dose of 20 mg/kg PHB given if seizures persist. Unresponsive subjects exit the study. All subjects received maintenance 1.5 mg/kg PHB mg/kg/dose given IV q8 hours continued for five days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="64"/>
                <participants group_id="P2" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Recieved Second Infusion of Same Drug</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Recieved Alternate Intervention</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received 2nd Infusion of Alternate Drug</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Modified ITT</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="60"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intravenous Levetiracetam</title>
          <description>Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance&#xD;
Intravenous levetiracetam: Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure.</description>
        </group>
        <group group_id="B2">
          <title>Intravenous Phenobarbital</title>
          <description>Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance&#xD;
Intravenous phenobarbital: Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load.</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="64"/>
            <count group_id="B2" value="42"/>
            <count group_id="B3" value="106"/>
          </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="64"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="106"/>
                  </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="33"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="64"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </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="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="23"/>
                  </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="45"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>New Zealand</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg)</title>
        <description>A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.&#xD;
Seizure cessation from 15 minutes after completion of infusion for 24 hours as assessed by continuous EEG reviewed by neurophysiologists.</description>
        <time_frame>24 hours</time_frame>
        <population>Treated participants with available primary outcome measure- EEG to 24 hours confirming seizure cessation.</population>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Levetiracetam</title>
            <description>Intravenous levetiracetam 40 - 60 mg/kg loading dose &amp; 10 mg/kg 8 hourly maintenance</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Phenobarbital</title>
            <description>Intravenous phenobarbital 20 - 40 mg/kg loading dose &amp; 1.5 mg/kg 8 hourly maintenance.</description>
          </group>
        </group_list>
        <measure>
          <title>Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg)</title>
          <description>A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.&#xD;
Seizure cessation from 15 minutes after completion of infusion for 24 hours as assessed by continuous EEG reviewed by neurophysiologists.</description>
          <population>Treated participants with available primary outcome measure- EEG to 24 hours confirming seizure cessation.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of 24 hour seizure termination rates using a Fisher's exact test.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment</title>
        <description>A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.</description>
        <time_frame>48 hours</time_frame>
        <population>Participants with evaluable data with 48 hours of seizure monitoring</population>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Levetiracetam</title>
            <description>Intravenous levetiracetam 40 - 60 mg/kg loading dose &amp; 10 mg/kg 8 hourly maintenance</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Phenobarbital</title>
            <description>Intravenous phenobarbital 20 - 40 mg/kg loading dose &amp; 1.5 mg/kg 8 hourly maintenance.</description>
          </group>
        </group_list>
        <measure>
          <title>Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment</title>
          <description>A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.</description>
          <population>Participants with evaluable data with 48 hours of seizure monitoring</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of seizure cessation at 48 hours using Fisher's exact test</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Neonates With Seizure Termination at 1 Hour After Treatment</title>
        <description>A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.</description>
        <time_frame>1 hour</time_frame>
        <population>Includes 1 participant in each arm who did not have data available for the primary end point at 24 hours</population>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Levetiracetam</title>
            <description>Intravenous levetiracetam 40 - 60 mg/kg loading dose &amp; 10 mg/kg 8 hourly maintenance</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Phenobarbital</title>
            <description>Intravenous phenobarbital 20 - 40 mg/kg loading dose &amp; 1.5 mg/kg 8 hourly maintenance.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Neonates With Seizure Termination at 1 Hour After Treatment</title>
          <description>A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.</description>
          <population>Includes 1 participant in each arm who did not have data available for the primary end point at 24 hours</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>LEV Dose Escalation Component</title>
        <description>Number of babies with seizure control at levetiracetam (60 mg/Kg load) who had not responded to 40 mg/kg load and number of babies with seizure control at 40 mg/kg who had not responded to 20 mg/kg.</description>
        <time_frame>24 hours</time_frame>
        <population>Babies who received any treatment of either phenobarbital or levetiracetam within the modified intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Levetiracetam</title>
            <description>Intravenous levetiracetam 40 mg/kg loading dose &amp; 10 mg/kg 8 hourly maintenance</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Phenobarbital</title>
            <description>Intravenous phenobarbital 20 mg/kg loading dose &amp; 1.5 mg/kg 8 hourly maintenance.</description>
          </group>
        </group_list>
        <measure>
          <title>LEV Dose Escalation Component</title>
          <description>Number of babies with seizure control at levetiracetam (60 mg/Kg load) who had not responded to 40 mg/kg load and number of babies with seizure control at 40 mg/kg who had not responded to 20 mg/kg.</description>
          <population>Babies who received any treatment of either phenobarbital or levetiracetam within the modified intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital Within the Hypoxic Ischemic Encephalopathy (HIE) Population and Treated With Hypothermia</title>
        <time_frame>24 hours</time_frame>
        <population>HIE participants with hypothermia treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Intravenous Levetiracetam</title>
            <description>Intravenous levetiracetam 40 - 60 mg/kg loading dose &amp; 10 mg/kg 8 hourly maintenance</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Phenobarbital</title>
            <description>Intravenous phenobarbital 20 - 40 mg/kg loading dose &amp; 1.5 mg/kg 8 hourly maintenance.</description>
          </group>
        </group_list>
        <measure>
          <title>Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital Within the Hypoxic Ischemic Encephalopathy (HIE) Population and Treated With Hypothermia</title>
          <population>HIE participants with hypothermia treatment</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Pharmacokinetic Data</title>
        <description>To obtain additional pharmacokinetic data &quot;Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax)&quot; of intravenous levetiracetam to confirm findings from our previous pharmacokinetic study.</description>
        <time_frame>48 hours</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Feasibility of Continuous Internet EEG Monitoring</title>
        <description>Feasibility of centralized remote access to continuous video EEG monitoring in the NICU via the internet</description>
        <time_frame>Subject study duration</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Evaluation of the Accuracy of Neonatal Seizure Detection Algorithm</title>
        <description>A novel neonatal seizure detection algorithm will be compared to the gold standard of two encephalographers reading 48 hours of neonatal video EEG in the measurement of seizure burden.</description>
        <time_frame>48 Hours</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Gather Safety Information on IV Levetiracetam</title>
        <description>Safety information to be collected includes daily recording of any adverse events during the 5 day treatment protocol.&#xD;
Complete Blood Count and Comprehensive Chemistry panels after 48 hours of treatment collected.</description>
        <time_frame>5 days</time_frame>
        <posting_date>09/2019</posting_date>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Imputation Sensitivity Analysis</title>
        <description>Analysis of missing data impact on the outcome measures</description>
        <time_frame>48 hours</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 5 days after treatment</time_frame>
      <desc>Data not collected separately for each intervention</desc>
      <group_list>
        <group group_id="E1">
          <title>Intravenous Phenobarbital</title>
          <description>Intravenous phenobarbital 20 mg/kg loading dose. If electrographic seizures persisted or recurred 15 minutes following completion of the infusion, subjects received a further 20 mg/kg PHB infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes following completion of the second infusion, the subject was then treated with LEV 40 mg/kg first. Another dose of 20 mg/kg PHB given if seizures persist. Unresponsive subjects exit the study. All subjects received maintenance 1.5 mg/kg PHB mg/kg/dose given IV q8 hours continued for five days.</description>
        </group>
        <group group_id="E2">
          <title>Intravenous Levetiracetam</title>
          <description>Intravenous levetiracetam 40 - 60 mg/kg loading dose. If electrographic seizures persisted or recurred 15 minutes following completion of the infusion, subjects received a further 20 mg/kg LEV infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes following completion of the second infusion, the subject was then treated with PHB 20 mg/kg. Another dose of 20 mg/kg PHB given if seizures persist. Unresponsive subjects exit the study. All subjects received maintenance LEV 10 mg/kg/dose given IV q8 hours continued for five days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Heart Rate Abnormality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Poor Feeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>New Medications</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Abnormality</sub_title>
                <description>Grade 4 respiratory distress thought probably or possibly due to study medication</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <description>Grade 4 hypotension thought probably or possibly due to study medications</description>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Heart Rate Abnormailty</sub_title>
                <description>Specific finding of heart rate abnormality on a day on which an adverse event was reported</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Vasopressor Requirement</sub_title>
                <description>Hypotension requiring vasopressor support on at least one day</description>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="42"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Poor Feeding</sub_title>
                <description>Specific finding of poor feeding on a day on which adverse event was documented</description>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>New Medical Problem</sub_title>
                <description>New Medical Problem reported on a day where an adverse event is documented</description>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>New Medications</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <description>Specific finding of infection on a day on which adverse event was documented</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Sedation</sub_title>
                <description>Specific finding of sedation on a day on which an adverse event was documented</description>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Abnormality</sub_title>
                <description>Specific finding of respiratory abnormality documented on a day on which an adverse event was documented</description>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <description>Specific finding of hypotension on a day on which an adverse event was indicated.</description>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="64"/>
              </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. Richard Haas</name_or_title>
      <organization>University of California San Diego, School of Medicine</organization>
      <phone>(858) 822-6700</phone>
      <email>rhaas@ucsd.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/NCT01720667
org study id: NoGA - R01 FD004147-01A1 Haas
secondary id: 1R01FD004147-01A1
nct id: NCT01720667
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
A new anticonvulsant, levetiracetam will be studied to treat seizures in newborn infants.
      Current treatments for the brain damaging complication of neonatal seizures are
      unsatisfactory.

      Monitoring for seizure detection will be tested at five (5) US sites and one (1)
      international site using the internet.
This project aims to improve the treatment of neonatal seizures. Current treatments are
      poorly effective and have significant side effects.

      Levetiracetam (LEV) has great potential as a treatment for neonatal seizures but is not
      approved for use in children less than 2 years of age.

      This study aims to obtain essential data regarding the efficacy and safety of LEV in this
      vulnerable and under researched population and simultaneously to develop EEG monitoring
      systems that facilitate seizure detection and research.

      Specific aims are:

        1. To determine the efficacy of intravenous LEV in terminating neonatal seizures when given
           as first line therapy.

        2. To obtain dose escalation data by studying the additional efficacy of a further dose in
           non responders.

        3. To obtain additional pharmacokinetic data to confirm findings from our previous
           pharmacokinetic study.

        4. To obtain further safety data of LEV in neonates.

        5. To prove the feasibility of centralized remote monitoring of continuous EEG monitoring
           in the Neonatal Intensive Care Unit (NICU) via the internet and test a promising
           automated neonatal seizure detection algorithm.

      The study design is a phase 2b randomized blinded controlled study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg)
time frame: 24 hours
description: A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.
Seizure cessation from 15 minutes after completion of infusion for 24 hours as assessed by continuous EEG reviewed by neurophysiologists.
measure: Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment
time frame: 48 hours
description: A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.
measure: Number of Neonates With Seizure Termination at 1 Hour After Treatment
time frame: 1 hour
description: A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.
measure: LEV Dose Escalation Component
time frame: 24 hours
description: Number of babies with seizure control at levetiracetam (60 mg/Kg load) who had not responded to 40 mg/kg load and number of babies with seizure control at 40 mg/kg who had not responded to 20 mg/kg.
measure: Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital Within the Hypoxic Ischemic Encephalopathy (HIE) Population and Treated With Hypothermia
time frame: 24 hours
measure: Pharmacokinetic Data
time frame: 48 hours
description: To obtain additional pharmacokinetic data "Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax)" of intravenous levetiracetam to confirm findings from our previous pharmacokinetic study.
measure: Feasibility of Continuous Internet EEG Monitoring
time frame: Subject study duration
description: Feasibility of centralized remote access to continuous video EEG monitoring in the NICU via the internet
measure: Evaluation of the Accuracy of Neonatal Seizure Detection Algorithm
time frame: 48 Hours
description: A novel neonatal seizure detection algorithm will be compared to the gold standard of two encephalographers reading 48 hours of neonatal video EEG in the measurement of seizure burden.
measure: Gather Safety Information on IV Levetiracetam
time frame: 5 days
description: Safety information to be collected includes daily recording of any adverse events during the 5 day treatment protocol.
Complete Blood Count and Comprehensive Chemistry panels after 48 hours of treatment collected.
arm group label: Intravenous levetiracetam
arm group type: Experimental
description: Intravenous levetiracetam 40 to 60 mg/kg loading dose. 10 mg/kg 8 hourly maintenance
arm group label: Intravenous phenobarbital
arm group type: Active Comparator
description: Intravenous phenobarbital 20 to 40 mg/kg load. 1.5 mg/kg 8 hourly maintenance
intervention type: Drug
intervention name: Intravenous levetiracetam
description: Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure.
arm group label: Intravenous levetiracetam
other name: Keppra
intervention type: Drug
intervention name: Intravenous phenobarbital
description: Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load.
arm group label: Intravenous phenobarbital
other name: phenobarbitone
criteria: 
gender: All
minimum age: 15 Minutes
maximum age: 14 Days
healthy volunteers: No
last name: Richard H Haas, MD
role: Principal Investigator
affiliation: University of California, San Diego
facility: 
country: United States
citation: Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012 Jul;72(1):43-9. doi: 10.1038/pr.2012.51. Epub 2012 Apr 11.
PMID: 22495532
citation: Sharpe C, Davis SL, Reiner GE, Lee LI, Gold JJ, Nespeca M, Wang SG, Joe P, Kuperman R, Gardner M, Honold J, Lane B, Knodel E, Rowe D, Battin MR, Bridge R, Goodmar J, Castro B, Rasmussen M, Arnell K, Harbert M, Haas R. Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected With Continuous Long-Term Neonatal Electroencephalography Monitoring. J Clin Neurophysiol. 2019 Jan;36(1):9-13. doi: 10.1097/WNP.0000000000000525.
PMID: 30289769
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, San Diego
investigator full name: Richard H. Haas
investigator title: Professor
mesh term: Seizures
mesh term: Levetiracetam
mesh term: Phenobarbital
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