<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/NCT02260258</url>
  </required_header>
  <id_info>
    <org_study_id>2014P000204</org_study_id>
    <secondary_id>14GRNT20010002</secondary_id>
    <nct_id>NCT02260258</nct_id>
  </id_info>
  <brief_title>Neuromuscular Blockade for Post-Cardiac Arrest Care</brief_title>
  <acronym>NMB_in_CA</acronym>
  <official_title>Neuromuscular Blockade for Post-Cardiac Arrest Care</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beth Israel Deaconess Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pittsburgh Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beaumont Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Beth Israel Deaconess Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to evaluate if neuromuscular blockade improves lactate&#xD;
      clearance (and preliminary secondary clinical outcome measures) as compared to usual care in&#xD;
      post-cardiac arrest patients undergoing targeted temperature management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Out-of-hospital cardiac arrest (OHCA) occurs in more than 300,000 patients in the United&#xD;
      States each year with an estimated mortality of greater than 90%. Unfortunately, we currently&#xD;
      have little to offer in terms of treatment other than supportive care for the post-cardiac&#xD;
      arrest patient. Neuromuscular blockade (NMB) is sometimes utilized in post-arrest patients&#xD;
      particularly for the prevention of shivering. However, usage of NMB remains controversial and&#xD;
      current American Heart Association (AHA) recommendations are to minimize utilization. Recent&#xD;
      prospective randomized trials in patients with acute respiratory distress syndrome suggest a&#xD;
      mortality benefit from NMB and an excellent safety profile. Furthermore, observational trials&#xD;
      in both sepsis and post-cardiac arrest show that the use of NMB is associated with improved&#xD;
      survival. Given this, we hypothesize that continuous NMB will be beneficial in post-arrest&#xD;
      patients. In order to test this hypothesis, we propose a multi-center, randomized,&#xD;
      open-label, phase II trial in post-CA patients comparing sustained NMB administration for 24&#xD;
      hours to standard of care after return of spontaenous circulation (ROSC). We will enroll&#xD;
      adult, comatose OHCA patients with ROSC and will utilize an already existing clinical trials&#xD;
      network for the completion of the study. Patients will be randomized to receive either&#xD;
      rocuronium for 24 hours or to receive placebo with usual care. Previous data from our group&#xD;
      has suggested that lactate levels in the post-arrest patient are a good surrogate marker for&#xD;
      mortality. We have therefore chosen to utilize lactate levels at 24 hours as the primary&#xD;
      endpoint for the current trial. Secondarily we will evaluate clinical endpoints including&#xD;
      length of stay (LOS), in-hospital mortality, and good neurological outcome. We will perform a&#xD;
      sub-study of inflammatory markers and oxygen consumption.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">May 29, 2019</completion_date>
  <primary_completion_date type="Actual">May 29, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Lactate Over 24 Hours</measure>
    <time_frame>24 hours</time_frame>
    <description>Change in median serum lactate level between enrollment and 24-hours after the receipt of study drug. A negative number indicates that the lactate levels were lower at 24 hours compared to their level at receipt of study drug.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Lactate Over 24 Hours: Effect Estimate</measure>
    <time_frame>24 hours</time_frame>
    <description>Interaction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time ROSC to Target Temperature</measure>
    <time_frame>Duration of hospitalization, limit 180 days</time_frame>
    <description>Time from return of spontaneous circulation to target temperature</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Intensive Care Unit (ICU) Stay</measure>
    <time_frame>Length of Stay Truncated at 28 Days</time_frame>
    <description>Length of stay in ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical Ventilation Duration</measure>
    <time_frame>Duration of hospitalization, limit 180 days</time_frame>
    <description>Mechanical Ventilation Duration in Hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>Duration of hospitalization, limit 180 days</time_frame>
    <description>In-hospital survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Rankin Score ≤3</measure>
    <time_frame>Duration of hospitalization, limit 180 days</time_frame>
    <description>Modified Rankin scale to assess neurological outcome at discharge. The scale ranges from 0 to 6, and is used for measuring the performance of daily activities. The score is as follows:&#xD;
0: No symptoms&#xD;
1: No significant disability (able to carry out all usual activities, despite some symptoms)&#xD;
2: Slight disability (able to look after own affairs without assistance, but unable to carry out all previous activities)&#xD;
3: Moderate disability (requires some help, but able to walk unassisted)&#xD;
4: Moderately severe disability (unable to attend to own bodily needs without assistance, and unable to walk unassisted)&#xD;
5: Severe disability (requires constant nursing care and attention, bedridden, incontinent)&#xD;
6: Dead.&#xD;
Higher cores represent worse outcomes. Good and bad neurological outcome will be defined as a score of 0-3 and 4-6 respectively. This outcome reports the number of patients with a good neurological outcome( modified Rankin score ≤ 3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle Weakness Score</measure>
    <time_frame>Duration of hospitalization, limit 180 days</time_frame>
    <description>Medical Research Council Scale : Measured for 6 muscle groups (3 in the upper limbs and 3 in the lower limbs). Maximum score is 30 (grade 5 for each group) and minimum is 0 (grade 0 for each group). If muscle group strength was not symmetric bilaterally, higher measurement used. Higher scores indicate better outcomes.&#xD;
Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance.&#xD;
Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed.&#xD;
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.&#xD;
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.&#xD;
Grade 0: No movement is observed</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">83</enrollment>
  <condition>Cardiac Arrest</condition>
  <arm_group>
    <arm_group_label>Rocuronium</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous intravenous (IV) infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual Care</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rocuronium</intervention_name>
    <description>Neuromuscular Blockade</description>
    <arm_group_label>Rocuronium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline</intervention_name>
    <description>Normal Saline</description>
    <arm_group_label>Usual Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult (≥ 18 years)&#xD;
&#xD;
          -  Cardiac arrest with sustained return of spontaneous circulation (ROSC)&#xD;
&#xD;
          -  Comatose (i.e., not following commands) following ROSC&#xD;
&#xD;
          -  Undergoing targeted temperature management (TTM)&#xD;
&#xD;
          -  Time of enrollment ≤ 6 hours from initiation of targeted temperature management&#xD;
&#xD;
          -  Serum Lactate ≥2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-existing dementia, severe brain injury, or dependence on others for activities of&#xD;
             daily living (i.e. a modified Rankin scale (mRS) score of 4 or higher)&#xD;
&#xD;
          -  Traumatic etiology of the cardiac arrest&#xD;
&#xD;
          -  Protected population (pregnant, prisoner)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael W Donnino, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Michael Kurz</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert Swor</name>
      <address>
        <city>Royal Oak</city>
        <state>Michigan</state>
        <zip>48073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 24, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <results_first_submitted>June 28, 2020</results_first_submitted>
  <results_first_submitted_qc>January 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 29, 2021</results_first_posted>
  <last_update_submitted>January 11, 2021</last_update_submitted>
  <last_update_submitted_qc>January 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beth Israel Deaconess Medical Center</investigator_affiliation>
    <investigator_full_name>Michael Donnino</investigator_full_name>
    <investigator_title>Michael Donnino MD</investigator_title>
  </responsible_party>
  <keyword>Cardiac Arrest, NMB, Neuromuscular Blockade, Rocuronium</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Arrest</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rocuronium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <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>June 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT02260258/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>June 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT02260258/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Between December 2014 and May 2019, we recruited adult patients (aged ≥18 years) who experienced a cardiac arrest and subsequently had sustained ROSC (≥20 minutes) but remained unresponsive and were undergoing TTM between 32℃ and 36℃. We added an additional inclusion criterion of a minimum serum lactate level of ≥2mmol/L early in study enrollment.</recruitment_details>
      <pre_assignment_details>Of 818 patients assessed for eligibility, 83 met inclusion criteria and were randomized to treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Rocuronium</title>
          <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
        </group>
        <group group_id="P2">
          <title>Usual Care</title>
          <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
                <participants group_id="P2" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>2 patients in NMB arm and 1 in control arm had clinical changes that precluded drug administration</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Rocuronium</title>
          <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
        </group>
        <group group_id="B2">
          <title>Usual Care</title>
          <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</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="37"/>
            <count group_id="B2" value="43"/>
            <count group_id="B3" value="80"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66" lower_limit="57" upper_limit="77"/>
                    <measurement group_id="B2" value="64" lower_limit="56" upper_limit="77"/>
                    <measurement group_id="B3" value="65" lower_limit="56" upper_limit="77"/>
                  </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="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race (n, % White)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race (n, % Black/African-American)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race (n, % Asian)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race (n, % American Indian/Native Alaskan)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race (n, % Other)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race (n, % Unknown/Not Reported)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="15"/>
                  </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="37"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past Medical History: Congestive Heart Failure</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past Medical History: Atrial Fibrillation</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past Medical History: Coronary Artery Disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past Medical History: Prior Cardiac Arrest</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <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>Past Medical History: Chronic Pulmonary Disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past Medical History: Liver Cirrhosis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past Medical History: Kidney Disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past Medical History: Active Malignancy</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Arrest Characteristics: Location (n, % Out of Hospital Cardiac Arrest)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Arrest Characteristics: Initial Rhythm (n, % Shockable)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Arrest Characteristics: Estimated Low-Flow Time (minutes, median, IQR)</title>
          <units>minutes</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4" lower_limit="0" upper_limit="7"/>
                    <measurement group_id="B2" value="2" lower_limit="0" upper_limit="10"/>
                    <measurement group_id="B3" value="3" lower_limit="0" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Arrest Characteristics: Witnessed (n, % yes)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Arrest Characteristics: Bystander Cardipulmonary Resuscitation (CPR) Provided (n, % yes)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Arrest Characteristics: Arrest Etiology (n, % cardiac)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Characteristics at Enrollment: Time from ROSC to Study Drug (hours, median, IQR)</title>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.5" lower_limit="6" upper_limit="8.3"/>
                    <measurement group_id="B2" value="6.3" lower_limit="5" upper_limit="7.5"/>
                    <measurement group_id="B3" value="6.5" lower_limit="5.2" upper_limit="7.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Characteristics at Enrollment: pH (median, IQR)</title>
          <units>pH</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.3" lower_limit="7.2" upper_limit="7.3"/>
                    <measurement group_id="B2" value="7.3" lower_limit="7.2" upper_limit="7.4"/>
                    <measurement group_id="B3" value="7.3" lower_limit="7.2" upper_limit="7.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Characteristics at Enrollment: Partial Pressure of Carbon Dioxide (pCO2) median, IQR</title>
          <units>mmHg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.5" lower_limit="34.5" upper_limit="53.5"/>
                    <measurement group_id="B2" value="40.0" lower_limit="33.5" upper_limit="48.5"/>
                    <measurement group_id="B3" value="41.5" lower_limit="34" upper_limit="49.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Characteristics at Enrollment: Partial Pressure of Oxygen (pO2) median, IQR</title>
          <units>mmHg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="100.0" lower_limit="76.0" upper_limit="168.5"/>
                    <measurement group_id="B2" value="161.0" lower_limit="83.0" upper_limit="245.0"/>
                    <measurement group_id="B3" value="132.5" lower_limit="79.5" upper_limit="232"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Characteristics at Enrollment: Shock Stratification (n, % shock)</title>
          <description>Shock stratification (n, %) refers to the number and percent of patients in each arm who were on vasopressors at the time of enrollment and therefore were considered to be in shock.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Characteristics at Enrollment: S-T Elevation Myocardial Infarction (STEMI) present (n, % yes)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Characteristics at Enrollment: Target temperature (median, IQR)</title>
          <units>celsius</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35" lower_limit="33.5" upper_limit="36"/>
                    <measurement group_id="B2" value="34" lower_limit="33.5" upper_limit="35.5"/>
                    <measurement group_id="B3" value="35" lower_limit="33.5" upper_limit="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Lactate Over 24 Hours</title>
        <description>Change in median serum lactate level between enrollment and 24-hours after the receipt of study drug. A negative number indicates that the lactate levels were lower at 24 hours compared to their level at receipt of study drug.</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rocuronium</title>
            <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
          </group>
          <group group_id="O2">
            <title>Usual Care</title>
            <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Lactate Over 24 Hours</title>
          <description>Change in median serum lactate level between enrollment and 24-hours after the receipt of study drug. A negative number indicates that the lactate levels were lower at 24 hours compared to their level at receipt of study drug.</description>
          <units>mmol/L</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2"/>
                    <measurement group_id="O2" value="-2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Lactate Over 24 Hours: Effect Estimate</title>
        <description>Interaction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups.</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Effect Estimate</title>
            <description>Value of the interaction term between allocated treatment and time, which is presented as a ratio of geometric mean differences over 24 hours. Values above 1.0 favor the placebo arm.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Lactate Over 24 Hours: Effect Estimate</title>
          <description>Interaction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups.</description>
          <units>Ratio</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" lower_limit="1.0" upper_limit="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time ROSC to Target Temperature</title>
        <description>Time from return of spontaneous circulation to target temperature</description>
        <time_frame>Duration of hospitalization, limit 180 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rocuronium</title>
            <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
          </group>
          <group group_id="O2">
            <title>Usual Care</title>
            <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Time ROSC to Target Temperature</title>
          <description>Time from return of spontaneous circulation to target temperature</description>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" lower_limit="5.3" upper_limit="9.4"/>
                    <measurement group_id="O2" value="8.3" lower_limit="4.7" upper_limit="11.2"/>
                  </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>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Time variable log transformed and compared using linear regression controlling for shock stratification and site. Effect estimate represents geometric mean difference. Values above 1.0 favor longer duration in the NMB arm.</non_inferiority_desc>
            <p_value>0.82</p_value>
            <p_value_desc>A priori threshold for significance 0.05</p_value_desc>
            <method>Regression, Linear</method>
            <param_type>Geometric mean difference</param_type>
            <param_value>1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.7</ci_lower_limit>
            <ci_upper_limit>1.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Intensive Care Unit (ICU) Stay</title>
        <description>Length of stay in ICU</description>
        <time_frame>Length of Stay Truncated at 28 Days</time_frame>
        <population>ICU survivors row include only the 14 patients in each arm who survived to ICU discharge (n=14 in each arm).</population>
        <group_list>
          <group group_id="O1">
            <title>Rocuronium</title>
            <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
          </group>
          <group group_id="O2">
            <title>Usual Care</title>
            <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Intensive Care Unit (ICU) Stay</title>
          <description>Length of stay in ICU</description>
          <population>ICU survivors row include only the 14 patients in each arm who survived to ICU discharge (n=14 in each arm).</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All patients</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" lower_limit="3.0" upper_limit="11.0"/>
                    <measurement group_id="O2" value="4.0" lower_limit="3.0" upper_limit="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ICU survivors</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0" lower_limit="6.0" upper_limit="16.0"/>
                    <measurement group_id="O2" value="5.0" lower_limit="4.0" upper_limit="12.0"/>
                  </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>All patients analyzed (N = 37 in NMB and 43 in Usual Care)</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>LOS truncated at 28 days and compared using negative binomial regression controlling for stratification and site. Effect estimates represent incidence rate ratios. The parameter estimate, p value and CI provided below are from the negative binomial regression carried out all patients (N = 37 in NMB and 43 in Usual Care)</non_inferiority_desc>
            <p_value>0.09</p_value>
            <method>Negative binomial regression</method>
            <param_type>Incidence rate ratio</param_type>
            <param_value>1.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.0</ci_lower_limit>
            <ci_upper_limit>1.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>ICU survivors alone analyzed (n = 14 in each arm)</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>LOS truncated at 28 days and compared using negative binomial regression controlling for stratification and site. Effect estimates represent incidence rate ratios. The parameter estimate, p value and CI provided below are from the negative binomial regression carried out on ICU survivors alone (n = 14 in NMB and 14 in Control)</non_inferiority_desc>
            <p_value>0.35</p_value>
            <method>Negative binomial regression</method>
            <param_type>Incidence rate ratio</param_type>
            <param_value>1.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.8</ci_lower_limit>
            <ci_upper_limit>2.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mechanical Ventilation Duration</title>
        <description>Mechanical Ventilation Duration in Hours</description>
        <time_frame>Duration of hospitalization, limit 180 days</time_frame>
        <population>Includes all patients, and also patients surviving to discontinuation of mechanical ventilation (n=14 in each group). Two patients discharged from the hospital on mechanical ventilation have duration truncated at time of discharge and are considered survivors to extubation.</population>
        <group_list>
          <group group_id="O1">
            <title>Rocuronium</title>
            <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
          </group>
          <group group_id="O2">
            <title>Usual Care</title>
            <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Mechanical Ventilation Duration</title>
          <description>Mechanical Ventilation Duration in Hours</description>
          <population>Includes all patients, and also patients surviving to discontinuation of mechanical ventilation (n=14 in each group). Two patients discharged from the hospital on mechanical ventilation have duration truncated at time of discharge and are considered survivors to extubation.</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All patients</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="102.0" lower_limit="64.3" upper_limit="206.4"/>
                    <measurement group_id="O2" value="82.7" lower_limit="47.4" upper_limit="160.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Survivors to extubation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="126.3" lower_limit="76.1" upper_limit="280.6"/>
                    <measurement group_id="O2" value="66.9" lower_limit="55.6" upper_limit="172.7"/>
                  </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>Anaysis for the full data (n= 37 in NMB and 43 in Control)</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Duration log transformed and compared using linear regression controlling for shock stratification and site. Includes all patients (n=37 in NMB and n = 43 in control). Effect estimates represent geometric mean difference. Values above 1.0 favor longer duration in the NMB arm.</non_inferiority_desc>
            <p_value>0.18</p_value>
            <method>Regression, Linear</method>
            <method_desc>Duration log transformed and so parameter estimate represents geometric mean difference.</method_desc>
            <param_type>Geometric mean difference</param_type>
            <param_value>1.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.9</ci_lower_limit>
            <ci_upper_limit>1.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Anaysis for the patients surviving to extubation (n= 14 in both groups)</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Duration log transformed and compared using linear regression controlling for shock stratification and site. Includes patients surviving to discontinuation of mechanical ventilation (n=14 in each group). Two patients discharged from the hospital on mechanical ventilation have duration truncated at time of discharge and are considered survivors to extubation. Effect estimates represent geometric mean difference. Values above 1.0 favor longer duration in the NMB arm.</non_inferiority_desc>
            <p_value>0.32</p_value>
            <method>Regression, Linear</method>
            <method_desc>Duration log transformed and so parameter estimate represents geometric mean difference.</method_desc>
            <param_type>Geometric mean difference</param_type>
            <param_value>1.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.7</ci_lower_limit>
            <ci_upper_limit>2.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Survival</title>
        <description>In-hospital survival</description>
        <time_frame>Duration of hospitalization, limit 180 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rocuronium</title>
            <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
          </group>
          <group group_id="O2">
            <title>Usual Care</title>
            <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Survival</title>
          <description>In-hospital survival</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="14"/>
                  </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>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparison made using logistic regression controlling for shock stratification and site. Effect estimates represent odds ratios</non_inferiority_desc>
            <p_value>0.63</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.5</ci_lower_limit>
            <ci_upper_limit>3.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Rankin Score ≤3</title>
        <description>Modified Rankin scale to assess neurological outcome at discharge. The scale ranges from 0 to 6, and is used for measuring the performance of daily activities. The score is as follows:&#xD;
0: No symptoms&#xD;
1: No significant disability (able to carry out all usual activities, despite some symptoms)&#xD;
2: Slight disability (able to look after own affairs without assistance, but unable to carry out all previous activities)&#xD;
3: Moderate disability (requires some help, but able to walk unassisted)&#xD;
4: Moderately severe disability (unable to attend to own bodily needs without assistance, and unable to walk unassisted)&#xD;
5: Severe disability (requires constant nursing care and attention, bedridden, incontinent)&#xD;
6: Dead.&#xD;
Higher cores represent worse outcomes. Good and bad neurological outcome will be defined as a score of 0-3 and 4-6 respectively. This outcome reports the number of patients with a good neurological outcome( modified Rankin score ≤ 3)</description>
        <time_frame>Duration of hospitalization, limit 180 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rocuronium</title>
            <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
          </group>
          <group group_id="O2">
            <title>Usual Care</title>
            <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Rankin Score ≤3</title>
          <description>Modified Rankin scale to assess neurological outcome at discharge. The scale ranges from 0 to 6, and is used for measuring the performance of daily activities. The score is as follows:&#xD;
0: No symptoms&#xD;
1: No significant disability (able to carry out all usual activities, despite some symptoms)&#xD;
2: Slight disability (able to look after own affairs without assistance, but unable to carry out all previous activities)&#xD;
3: Moderate disability (requires some help, but able to walk unassisted)&#xD;
4: Moderately severe disability (unable to attend to own bodily needs without assistance, and unable to walk unassisted)&#xD;
5: Severe disability (requires constant nursing care and attention, bedridden, incontinent)&#xD;
6: Dead.&#xD;
Higher cores represent worse outcomes. Good and bad neurological outcome will be defined as a score of 0-3 and 4-6 respectively. This outcome reports the number of patients with a good neurological outcome( modified Rankin score ≤ 3)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="9"/>
                  </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>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparison made using logistic regression controlling for shock stratification and site. Effect estimates represent odds ratios</non_inferiority_desc>
            <p_value>0.35</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>4.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Muscle Weakness Score</title>
        <description>Medical Research Council Scale : Measured for 6 muscle groups (3 in the upper limbs and 3 in the lower limbs). Maximum score is 30 (grade 5 for each group) and minimum is 0 (grade 0 for each group). If muscle group strength was not symmetric bilaterally, higher measurement used. Higher scores indicate better outcomes.&#xD;
Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance.&#xD;
Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed.&#xD;
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.&#xD;
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.&#xD;
Grade 0: No movement is observed</description>
        <time_frame>Duration of hospitalization, limit 180 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rocuronium</title>
            <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
          </group>
          <group group_id="O2">
            <title>Usual Care</title>
            <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</description>
          </group>
        </group_list>
        <measure>
          <title>Muscle Weakness Score</title>
          <description>Medical Research Council Scale : Measured for 6 muscle groups (3 in the upper limbs and 3 in the lower limbs). Maximum score is 30 (grade 5 for each group) and minimum is 0 (grade 0 for each group). If muscle group strength was not symmetric bilaterally, higher measurement used. Higher scores indicate better outcomes.&#xD;
Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance.&#xD;
Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed.&#xD;
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.&#xD;
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.&#xD;
Grade 0: No movement is observed</description>
          <units>Points</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30" lower_limit="28" upper_limit="30"/>
                    <measurement group_id="O2" value="30" lower_limit="27" upper_limit="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From time of enrollment to time of discharge, an average of 7.2 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Rocuronium</title>
          <description>Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.&#xD;
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).&#xD;
Rocuronium: Neuromuscular Blockade</description>
        </group>
        <group group_id="E2">
          <title>Usual Care</title>
          <description>Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.&#xD;
Normal Saline: Normal Saline</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="23" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
              </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="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
              </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>Mike Donnino</name_or_title>
      <organization>BIDMC</organization>
      <phone>6177542882</phone>
      <email>mdonnino@bidmc.harvard.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/NCT02260258
org study id: 2014P000204
secondary id: 14GRNT20010002
nct id: NCT02260258
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The main purpose of this study is to evaluate if neuromuscular blockade improves lactate
      clearance (and preliminary secondary clinical outcome measures) as compared to usual care in
      post-cardiac arrest patients undergoing targeted temperature management.
Out-of-hospital cardiac arrest (OHCA) occurs in more than 300,000 patients in the United
      States each year with an estimated mortality of greater than 90%. Unfortunately, we currently
      have little to offer in terms of treatment other than supportive care for the post-cardiac
      arrest patient. Neuromuscular blockade (NMB) is sometimes utilized in post-arrest patients
      particularly for the prevention of shivering. However, usage of NMB remains controversial and
      current American Heart Association (AHA) recommendations are to minimize utilization. Recent
      prospective randomized trials in patients with acute respiratory distress syndrome suggest a
      mortality benefit from NMB and an excellent safety profile. Furthermore, observational trials
      in both sepsis and post-cardiac arrest show that the use of NMB is associated with improved
      survival. Given this, we hypothesize that continuous NMB will be beneficial in post-arrest
      patients. In order to test this hypothesis, we propose a multi-center, randomized,
      open-label, phase II trial in post-CA patients comparing sustained NMB administration for 24
      hours to standard of care after return of spontaenous circulation (ROSC). We will enroll
      adult, comatose OHCA patients with ROSC and will utilize an already existing clinical trials
      network for the completion of the study. Patients will be randomized to receive either
      rocuronium for 24 hours or to receive placebo with usual care. Previous data from our group
      has suggested that lactate levels in the post-arrest patient are a good surrogate marker for
      mortality. We have therefore chosen to utilize lactate levels at 24 hours as the primary
      endpoint for the current trial. Secondarily we will evaluate clinical endpoints including
      length of stay (LOS), in-hospital mortality, and good neurological outcome. We will perform a
      sub-study of inflammatory markers and oxygen consumption.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Participant)
measure: Change in Lactate Over 24 Hours
time frame: 24 hours
description: Change in median serum lactate level between enrollment and 24-hours after the receipt of study drug. A negative number indicates that the lactate levels were lower at 24 hours compared to their level at receipt of study drug.
measure: Change in Lactate Over 24 Hours: Effect Estimate
time frame: 24 hours
description: Interaction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups.
measure: Time ROSC to Target Temperature
time frame: Duration of hospitalization, limit 180 days
description: Time from return of spontaneous circulation to target temperature
measure: Length of Intensive Care Unit (ICU) Stay
time frame: Length of Stay Truncated at 28 Days
description: Length of stay in ICU
measure: Mechanical Ventilation Duration
time frame: Duration of hospitalization, limit 180 days
description: Mechanical Ventilation Duration in Hours
measure: Survival
time frame: Duration of hospitalization, limit 180 days
description: In-hospital survival
measure: Number of Participants With Rankin Score ≤3
time frame: Duration of hospitalization, limit 180 days
description: Modified Rankin scale to assess neurological outcome at discharge. The scale ranges from 0 to 6, and is used for measuring the performance of daily activities. The score is as follows:
0: No symptoms
1: No significant disability (able to carry out all usual activities, despite some symptoms)
2: Slight disability (able to look after own affairs without assistance, but unable to carry out all previous activities)
3: Moderate disability (requires some help, but able to walk unassisted)
4: Moderately severe disability (unable to attend to own bodily needs without assistance, and unable to walk unassisted)
5: Severe disability (requires constant nursing care and attention, bedridden, incontinent)
6: Dead.
Higher cores represent worse outcomes. Good and bad neurological outcome will be defined as a score of 0-3 and 4-6 respectively. This outcome reports the number of patients with a good neurological outcome( modified Rankin score ≤ 3)
measure: Muscle Weakness Score
time frame: Duration of hospitalization, limit 180 days
description: Medical Research Council Scale : Measured for 6 muscle groups (3 in the upper limbs and 3 in the lower limbs). Maximum score is 30 (grade 5 for each group) and minimum is 0 (grade 0 for each group). If muscle group strength was not symmetric bilaterally, higher measurement used. Higher scores indicate better outcomes.
Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance.
Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed.
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.
Grade 0: No movement is observed
arm group label: Rocuronium
arm group type: Experimental
description: Patients will receive a bolus dose of 1 mg/kg, then a continuous intravenous (IV) infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
arm group label: Usual Care
arm group type: Placebo Comparator
description: Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
intervention type: Drug
intervention name: Rocuronium
description: Neuromuscular Blockade
arm group label: Rocuronium
intervention type: Drug
intervention name: Normal Saline
description: Normal Saline
arm group label: Usual Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael W Donnino, MD
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Beth Israel Deaconess Medical Center
investigator full name: Michael Donnino
investigator title: Michael Donnino MD
mesh term: Heart Arrest
mesh term: Rocuronium
sharing ipd: Undecided
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 