Neuromuscular Blockade for Post-Cardiac Arrest Care (NMB_in_CA)

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: Cardiac Arrest
• Intervention / Treatment: Drug: Rocuronium; Drug: Normal Saline

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

Study Locations

• United States
  • 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

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

How is the study designed?

Design Details

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

Number of Arms

2

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).	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Lactate Over 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	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 from return of spontaneous circulation to target temperature	Duration of hospitalization, limit 180 days
Length of Intensive Care Unit (ICU) Stay	Length of stay in ICU	Length of Stay Truncated at 28 Days
Mechanical Ventilation Duration	Mechanical Ventilation Duration in Hours	Duration of hospitalization, limit 180 days
Survival	In-hospital survival	Duration of hospitalization, limit 180 days
Number of Participants With Rankin Score ≤3	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	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

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: University of Alabama at Birmingham; Brigham and Women's Hospital; University of Pittsburgh Medical Center; Beaumont Hospital

Publications and helpful links

General 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.

Study record dates

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

• Keywords: Cardiac Arrest, NMB, Neuromuscular Blockade, Rocuronium
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Rocuronium
• Other Study ID Numbers: 2014P000204; 14GRNT20010002 (Other Grant/Funding Number: American Heart Association)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided