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Neuromuscular Blockade for Post-Cardiac Arrest Care (NMB_in_CA)

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ClinicalTrials.gov Identifier: NCT02260258
Recruitment Status : Completed
First Posted : October 9, 2014
Results First Posted : January 29, 2021
Last Update Posted : January 29, 2021
Sponsor:
Collaborators:
University of Pittsburgh Medical Center
Brigham and Women's Hospital
University of Alabama at Birmingham
Beaumont Hospital
Information provided by (Responsible Party):
Michael Donnino, Beth Israel Deaconess Medical Center

Tracking Information
First Submitted Date  ICMJE September 24, 2014
First Posted Date  ICMJE October 9, 2014
Results First Submitted Date  ICMJE June 28, 2020
Results First Posted Date  ICMJE January 29, 2021
Last Update Posted Date January 29, 2021
Study Start Date  ICMJE October 2014
Actual Primary Completion Date May 29, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2021)
  • Change in Lactate Over 24 Hours [ Time Frame: 24 hours ]
    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.
  • Change in Lactate Over 24 Hours: Effect Estimate [ Time Frame: 24 hours ]
    Interaction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups.
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
Lactate levels 24 hours after initiation of study drug [ Time Frame: 24 hours ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2021)
  • Time ROSC to Target Temperature [ Time Frame: Duration of hospitalization, limit 180 days ]
    Time from return of spontaneous circulation to target temperature
  • Length of Intensive Care Unit (ICU) Stay [ Time Frame: Length of Stay Truncated at 28 Days ]
    Length of stay in ICU
  • Mechanical Ventilation Duration [ Time Frame: Duration of hospitalization, limit 180 days ]
    Mechanical Ventilation Duration in Hours
  • Survival [ Time Frame: Duration of hospitalization, limit 180 days ]
    In-hospital survival
  • Number of Participants With Rankin Score ≤3 [ Time Frame: Duration of hospitalization, limit 180 days ]
    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)
  • Muscle Weakness Score [ Time Frame: Duration of hospitalization, limit 180 days ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
  • Lactate change over time [ Time Frame: (0, 12, 24, 36-hours) ]
  • Survival [ Time Frame: Duration of hospitalization, limit 180 days ]
    In-hospital survival
  • Good neurological outcome [ Time Frame: Duration of hospitalization, limit 180 days ]
    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.
    Good and bad neurological outcome will be defined as a score of 0-3 and 4-6 respectively.
  • Length of Intensive Care Unit (ICU) Stay [ Time Frame: Duration of ICU stay, limit 180 days ]
    Time from study drug to ICU discharge
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neuromuscular Blockade for Post-Cardiac Arrest Care
Official Title  ICMJE Neuromuscular Blockade for Post-Cardiac Arrest Care
Brief Summary 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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Other
Condition  ICMJE Cardiac Arrest
Intervention  ICMJE
  • Drug: Rocuronium
    Neuromuscular Blockade
  • Drug: Normal Saline
    Normal Saline
Study Arms  ICMJE
  • Experimental: Rocuronium

    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).

    Intervention: Drug: Rocuronium
  • Placebo Comparator: Usual Care
    Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
    Intervention: Drug: Normal Saline
Publications * Moskowitz A, Andersen LW, Rittenberger JC, Swor R, Seethala RR, Kurz MC, Berg KM, Chase M, Cocchi MN, Grossestreuer AV, Liu X, Holmberg MJ, Callaway CW, Donnino MW. Continuous Neuromuscular Blockade Following Successful Resuscitation From Cardiac Arrest: A Randomized Trial. J Am Heart Assoc. 2020 Sep;9(17):e017171. doi: 10.1161/JAHA.120.017171. Epub 2020 Aug 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 11, 2021)
83
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2014)
80
Actual Study Completion Date  ICMJE May 29, 2019
Actual Primary Completion Date May 29, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult (≥ 18 years)
  • Cardiac arrest with sustained return of spontaneous circulation (ROSC)
  • Comatose (i.e., not following commands) following ROSC
  • Undergoing targeted temperature management (TTM)
  • Time of enrollment ≤ 6 hours from initiation of targeted temperature management
  • Serum Lactate ≥2

Exclusion Criteria:

  • Pre-existing dementia, severe brain injury, or dependence on others for activities of daily living (i.e. a modified Rankin scale (mRS) score of 4 or higher)
  • Traumatic etiology of the cardiac arrest
  • Protected population (pregnant, prisoner)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02260258
Other Study ID Numbers  ICMJE 2014P000204
14GRNT20010002 ( Other Grant/Funding Number: American Heart Association )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Michael Donnino, Beth Israel Deaconess Medical Center
Study Sponsor  ICMJE Beth Israel Deaconess Medical Center
Collaborators  ICMJE
  • University of Pittsburgh Medical Center
  • Brigham and Women's Hospital
  • University of Alabama at Birmingham
  • Beaumont Hospital
Investigators  ICMJE
Principal Investigator: Michael W Donnino, MD Beth Israel Deaconess Medical Center
PRS Account Beth Israel Deaconess Medical Center
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP