Neuromuscular Blockade for Post-Cardiac Arrest Care (NMB_in_CA)

January 11, 2021 updated by: Michael Donnino, Beth Israel Deaconess Medical Center
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.

Study Overview

Status

Completed

Conditions

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

Interventional

Enrollment (Actual)

83

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Michael Kurz
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02215
        • Brigham and Women's Hospital
    • Michigan
      • Royal Oak, Michigan, United States, 48073
        • Robert Swor
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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).

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.
Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 hours
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.
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time ROSC to Target Temperature
Time Frame: Duration of hospitalization, limit 180 days
Time from return of spontaneous circulation to target temperature
Duration of hospitalization, limit 180 days
Length of Intensive Care Unit (ICU) Stay
Time Frame: Length of Stay Truncated at 28 Days
Length of stay in ICU
Length of Stay Truncated at 28 Days
Mechanical Ventilation Duration
Time Frame: Duration of hospitalization, limit 180 days
Mechanical Ventilation Duration in Hours
Duration of hospitalization, limit 180 days
Survival
Time Frame: Duration of hospitalization, limit 180 days
In-hospital survival
Duration of hospitalization, limit 180 days
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)

Duration of hospitalization, limit 180 days
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

Duration of hospitalization, limit 180 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Actual)

May 29, 2019

Study Completion (Actual)

May 29, 2019

Study Registration Dates

First Submitted

September 24, 2014

First Submitted That Met QC Criteria

October 6, 2014

First Posted (Estimate)

October 9, 2014

Study Record Updates

Last Update Posted (Actual)

January 29, 2021

Last Update Submitted That Met QC Criteria

January 11, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cardiac Arrest

Clinical Trials on Rocuronium

3
Subscribe