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Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest (RELAX)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by Medical University of Vienna.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Heidrun Losert, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01719770
First received: July 6, 2011
Last updated: October 30, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Cardiac Arrest With Successful Resuscitation
Hypothermia
Skeletal Muscle Relaxant Overdose
Drug: rocuronium
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Requirement of Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest - a Pilot Study

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Number of shivering episodes [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Shivering episodes will be detected according to the Shivering Assessment Scale


Secondary Outcome Measures:
  • Elapsed time to target temperature [ Time Frame: Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation ] [ Designated as safety issue: No ]
  • Dissipated energy to reach the target temperature [ Time Frame: Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation ] [ Designated as safety issue: No ]
  • Changes in basal metabolism due to shivering or elevated stress levels [ Time Frame: during the first 72 hours after cardiac arrest ] [ Designated as safety issue: No ]
  • Depth of relaxation [ Time Frame: during cooling and rewarming period, which will be approximately 30 hours up to 48 hours after initiation of cooling ] [ Designated as safety issue: Yes ]
    via train of four measurement

  • Changes in serum levels of midazolam, fentanyl and rocuronium [ Time Frame: within the first 48 hours of treatment ] [ Designated as safety issue: Yes ]
  • Number of necessary boli of rocuronium [ Time Frame: during colling 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 ] [ Designated as safety issue: Yes ]
    In case of a shivering episode, a bolus of rocuronium will be administered (0,25mg/kg)


Estimated Enrollment: 60
Study Start Date: November 2010
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rocuronium
Continuous infusion of rocuronium with 0,25mg/kg (blinded) for 29 hours after initiation of mild therapeutic hypothermia
Drug: rocuronium
continuous application of rocuronium 0,25mg/kg/h (blinded), in case of shivering episode bolus sodium-chloride (blinded)
Other Name: Esmeron
Placebo Comparator: Placebo
Continuous infusion of sodium-chloride (placebo) and rocuronium bolus (0,25mg/kg)in case of shivering episode (blinded)
Other: placebo
continuous infusion of sodium-chloride (blinded), in case of shivering episode application of rocuronium 0,25mg/kg (blinded)
Other Name: sodium-chloride

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01719770

Contacts
Contact: Heidrun Losert, MD 00431404001964 heidrun.losert@meduniwien.ac.at
Contact: Mathias Stöckl, MD 00431404001964 mathias.stoeckl@meduniwien.ac.at

Locations
Austria
Medical University of Vienna, Department of Emergency Medicine Recruiting
Vienna, Austria, 1190
Contact: Heidrun Losert, MD    00431404001964    heidrun.losert@meduniwien.ac.at   
Contact: Mathias Stöckl, MD    00431404001964    mathias.stoeckl@meduniwien.ac.at   
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Heidrun Losert, MD Medical University Vienna, Department of Emergency Medicine
  More Information

No publications provided

Responsible Party: Heidrun Losert, Priv. Doz. Dr. Heidrun Losert, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01719770     History of Changes
Other Study ID Numbers: RELAX1
Study First Received: July 6, 2011
Last Updated: October 30, 2012
Health Authority: Austria: Ethikkommission

Keywords provided by Medical University of Vienna:
cardiac arrest
therapeutic hypothermia
skeletal muscle paralysis
shivering
serum drug levels
basal metabolism

Additional relevant MeSH terms:
Heart Arrest
Hypothermia
Muscle Hypotonia
Paralysis
Body Temperature Changes
Cardiovascular Diseases
Heart Diseases
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Manifestations
Signs and Symptoms
Rocuronium
Neuromuscular Agents
Neuromuscular Blocking Agents
Neuromuscular Nondepolarizing Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014