Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest

NCT01719770 | Completed Phase 3 DMC

• 1 other identifier: RELAX1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Mild hypothermia improves neurological outcome after cardiac arrest. Neuromuscular blockers are in use, together with analgesia and sedation, during the cooling process in many centers to prevent shivering. Since neuromuscular blockers are accused to be associated with various side effects causing serious harm and/or leading to prolong ICU stay. So economical use seems to be reasonable. Furthermore, the use of neuromuscular blockers may mask epileptic activity. Therefore, post hypoxic seizures might remain undetected. Aim of this study is to investigate if a continuous application of neuromuscular blockers is necessary to prevent shivering and thereby avoid the counter regulation to achieve the target temperature as soon as possible in mild hypothermic therapy after cardiac arrest. A single center (university hospital) study. Randomized, double blinded, double dummy study design. Eligible are all adult patients after successful resuscitation due to cardiac arrest of presumed cardiac origin. All patients receiving mild therapeutic hypothermia after cardiac arrest of presumed cardiopulmonary origin will be included. Patients \<18 years, cardiac arrest \>6 hours before admittance at the hospital, patients with known or clinically apparent pregnancy, patients who reach our hospital with a body temperature below 35°C, patients with known allergic reactions against rocuronium, patients with a history of myasthenia gravis, patients with obvious intoxication, wards of the state/prisoners and patients with known epileptic disease will be excluded. Primary outcome: Shivering episodes will be scored with the Shivering Assessment Scale. Secondary outcome: Total doses of rocuronium, time to target core temperature of 33°C, dissipated energy and total energy needed during the cooling period will be compared between the two groups. Changes in basal metabolism and depth of relaxation will be ascertained. Furthermore, serum levels of midazolam, fentanyl, rocuronium and stress hormones will be measured. Train-of-four will be performed to assess the depth of relaxation. Sedation will be monitored via bispectral index; measurement of metabolic activity will be evaluated using indirect calorimetry. Additionally, EEG will be performed to detect epileptiform activities. Blood will be drawn to measure levels of midazolam, fentanyl and rocuronium.

Conditions

Cardiac Arrest With Successful Resuscitation; Hypothermia; Skeletal Muscle Relaxant Overdose

Keywords

cardiac arrest; therapeutic hypothermia; skeletal muscle paralysis; shivering; serum drug levels; basal metabolism

Outcome Measures

Primary Outcomes (1)

• Number of shivering episodes

  Shivering episodes will be detected according to the Shivering Assessment Scale

  during cooling period (mild therapeutic hypothermia will be performed for 24 hours after cooling initiation, rewarming with 0,4°C per hour until a body core temperature of 36°C is reached); total time of approximately 31 hours

Secondary Outcomes (6)

• Elapsed time to target temperature

  Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation

• Dissipated energy to reach the target temperature

  Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation

• Changes in basal metabolism due to shivering or elevated stress levels

  during the first 72 hours after cardiac arrest

• Depth of relaxation

  during cooling and rewarming period, which will be approximately 30 hours up to 48 hours after initiation of cooling

• Changes in serum levels of midazolam, fentanyl and rocuronium

  within the first 48 hours of treatment

Study Arms (2)

Rocuronium

ACTIVE COMPARATOR

Continuous infusion of rocuronium with 0,25mg/kg (blinded) for 29 hours after initiation of mild therapeutic hypothermia

Drug: rocuronium

Placebo

PLACEBO COMPARATOR

Continuous infusion of sodium-chloride (placebo) and rocuronium bolus (0,25mg/kg)in case of shivering episode (blinded)

Other: placebo

Interventions

rocuronium DRUG

continuous application of rocuronium 0,25mg/kg/h (blinded), in case of shivering episode bolus sodium-chloride (blinded)

Also known as: Esmeron

Rocuronium

placebo OTHER

continuous infusion of sodium-chloride (blinded), in case of shivering episode application of rocuronium 0,25mg/kg (blinded)

Also known as: sodium-chloride

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• all patients receiving mild therapeutic hypothermia after cardiac arrest
• cardiac arrest due to cardiopulmonary origin

You may not qualify if:

• patients younger than 18 years
• traumatic cardiac arrest
• cardiac arrest due to exsanguination, strangulation, smoke inhalation, drug overdose, electrocution, hanging or drowning
• known or clinically apparent pregnancy
• no treatment with mild therapeutic hypothermia because of an AND order
• terminal illness
• a body core temperature below 35°C at hospital admission
• known allergic reaction against rocuronium
• history of myasthenia gravis
• obvious intoxication
• ward of the state or prisoner
• known epileptic disease
• cardiac arrest \>6 hours prior to hospital admission

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna, Department of Emergency Medicine

Vienna, Vienna, 1190, Austria

Location

MeSH Terms

Conditions

Hypothermia; Heart Arrest

Interventions

Rocuronium; Sodium Chloride

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Heidrun Losert, MD

  Medical University Vienna, Department of Emergency Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Priv. Doz. Dr. Heidrun Losert

Study Record Dates

• First Submitted: July 6, 2011
• First Posted: November 1, 2012
• Study Start: November 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: April 1, 2015
• Last Updated: May 1, 2015

Record last verified: 2015-04

Locations

AU (1)