Neuromuscular Blockade for Post-Cardiac Arrest Care

NCT ID: NCT02260258

Last Updated: 2021-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2019-05-29

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.

Conditions

Cardiac Arrest

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: EXPERIMENTAL

Rocuronium

Intervention Type: DRUG

Neuromuscular Blockade

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.

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: DRUG

Normal Saline

Interventions

Rocuronium

Neuromuscular Blockade

Intervention Type: DRUG

Normal Saline

Normal Saline

Intervention Type: DRUG

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh Medical Center

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Beaumont Hospital

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Michael Donnino

Michael Donnino MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael W Donnino, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Michael Kurz

Birmingham, Alabama, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Robert Swor

Royal Oak, Michigan, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32851921 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

14GRNT20010002

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2014P000204

Identifier Type: -

Identifier Source: org_study_id