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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

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.

Condition or disease Intervention/treatment Phase
Cardiac Arrest Drug: Rocuronium Drug: Normal Saline Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 83 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Other
Official Title: Neuromuscular Blockade for Post-Cardiac Arrest Care
Study Start Date : October 2014
Actual Primary Completion Date : May 29, 2019
Actual Study Completion Date : May 29, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cardiac Arrest

Arm Intervention/treatment
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).

Drug: Rocuronium
Neuromuscular Blockade

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.
Drug: Normal Saline
Normal Saline




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Time ROSC to Target Temperature [ Time Frame: Duration of hospitalization, limit 180 days ]
    Time from return of spontaneous circulation to target temperature

  2. Length of Intensive Care Unit (ICU) Stay [ Time Frame: Length of Stay Truncated at 28 Days ]
    Length of stay in ICU

  3. Mechanical Ventilation Duration [ Time Frame: Duration of hospitalization, limit 180 days ]
    Mechanical Ventilation Duration in Hours

  4. Survival [ Time Frame: Duration of hospitalization, limit 180 days ]
    In-hospital survival

  5. 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)


  6. 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




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02260258


Locations
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United States, Alabama
Michael Kurz
Birmingham, Alabama, United States, 35294
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
United States, Michigan
Robert Swor
Royal Oak, Michigan, United States, 48073
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
University of Pittsburgh Medical Center
Brigham and Women's Hospital
University of Alabama at Birmingham
Beaumont Hospital
Investigators
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Principal Investigator: Michael W Donnino, MD Beth Israel Deaconess Medical Center
  Study Documents (Full-Text)

Documents provided by Michael Donnino, Beth Israel Deaconess Medical Center:
Statistical Analysis Plan  [PDF] June 7, 2019
Study Protocol  [PDF] June 7, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Michael Donnino, Michael Donnino MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT02260258    
Other Study ID Numbers: 2014P000204
14GRNT20010002 ( Other Grant/Funding Number: American Heart Association )
First Posted: October 9, 2014    Key Record Dates
Results First Posted: January 29, 2021
Last Update Posted: January 29, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Michael Donnino, Beth Israel Deaconess Medical Center:
Cardiac Arrest, NMB, Neuromuscular Blockade, Rocuronium
Additional relevant MeSH terms:
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Heart Arrest
Heart Diseases
Cardiovascular Diseases
Rocuronium
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs