Clinical trial NCT02260258: Neuromuscular Blockade for Post-Cardiac Arrest Care
Official title: Neuromuscular Blockade for Post-Cardiac Arrest Care
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiac Arrest
Keywords: Cardiac Arrest, NMB, Neuromuscular Blockade, Rocuronium
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh Medical Center
name: Brigham and Women's Hospital
name: University of Alabama at Birmingham
name: Beaumont Hospital
First posted: 2014-10-09
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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)

Primary outcomes:
measure: Change in Lactate Over 24 Hours
timeFrame: 24 hours
measure: Change in Lactate Over 24 Hours: Effect Estimate
timeFrame: 24 hours
Secondary outcomes:
measure: Time ROSC to Target Temperature
timeFrame: Duration of hospitalization, limit 180 days
measure: Length of Intensive Care Unit (ICU) Stay
timeFrame: Length of Stay Truncated at 28 Days
measure: Mechanical Ventilation Duration
timeFrame: Duration of hospitalization, limit 180 days
measure: Survival
timeFrame: Duration of hospitalization, limit 180 days
measure: Number of Participants With Rankin Score ≤3
timeFrame: Duration of hospitalization, limit 180 days
measure: Muscle Weakness Score
timeFrame: Duration of hospitalization, limit 180 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Michael Kurz
state: Alabama
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Royal Oak
country: United States
facility: Robert Swor
state: Michigan
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Michael W Donnino, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.