Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Pilot Study of Intra-arrest Therapeutic Hypothermia in Patients Suffering Non-Traumatic Out of Hospital Cardiac Arrest

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jonathan Studnek, Carolinas Medical Center
ClinicalTrials.gov Identifier:
NCT01413399
First received: August 9, 2011
Last updated: August 3, 2012
Last verified: August 2012

August 9, 2011
August 3, 2012
August 2011
June 2012   (final data collection date for primary outcome measure)
Survival to hospital discharge [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks ] [ Designated as safety issue: No ]
Survival to hospital discharge [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks ]
Complete list of historical versions of study NCT01413399 on ClinicalTrials.gov Archive Site
  • Number of patients who achieve prehospital return of spontaneous circulation [ Time Frame: Patients will be followed for the duration of their prehospital course of care expected to be an average of 1 hour ] [ Designated as safety issue: No ]
    ROSC will be defined as return of sustained pulses during the prehospital cardiac arrest resuscitation
  • Total volume of chilled saline infused [ Time Frame: Assessed at the end of prehospital care likely 30-90 min. after resuscitation was initiated ] [ Designated as safety issue: No ]
  • Number of patients who achieve prehospital return of spontaneous circulation [ Time Frame: Patients will be followed for the duration of their prehospital course of care expected to be an average of 1 hour ]
    ROSC will be defined as return of sustained pulses during the prehospital cardiac arrest resuscitation
  • Total volume of chilled saline infused
Not Provided
Not Provided
 
A Pilot Study of Intra-arrest Therapeutic Hypothermia in Patients Suffering Non-Traumatic Out of Hospital Cardiac Arrest
A Pilot Study of Intra-arrest Therapeutic Hypothermia in Patients Suffering Non-Traumatic Out of Hospital Cardiac Arrest

The objective of this study will be to assess the frequency of return of spontaneous circulation (ROSC), survival to admission, survival to discharge from the hospital, and neurologic function at time of discharge from the hospital among patients experiencing out of hospital cardiac arrest randomized to receive either intra-arrest induction of therapeutic hypothermia (IATH) or post-arrest therapeutic hypothermia (TH).

Specific aims

  1. Develop and test methodologies for randomizing out-of-hospital cardiac arrest (OOHCA) patients to receive one of two therapeutic hypothermia treatments in the prehospital environment.
  2. Randomize patients experiencing OOHCA to receive either IATH or post-arrest TH and assess the frequency of ROSC, survival to admission, survival to discharge, and neurologic function.
  3. Estimate the most efficacious volume of chilled saline administered during the intra arrest period.
  4. Identify barriers and strategies for the successful implementation of this project as a multicenter randomized trial.

Therapeutic hypothermia improves mortality and functional neurologic outcomes in patients resuscitated from pulseless ventricular tachycardia and fibrillation (VT/VF), with several studies validating the safety of prehospital induction following successful (return of spontaneous circulation) ROSC by the rapid infusion of 2 liters of 4ºC intravenous fluids. However, the optimal timing for inducing hypothermia remains uncertain. Early studies demonstrated the efficacy of therapeutic hypothermia despite delays of 4 to 8 hours from the time of ROSC to the initiation of cooling. The post-resuscitation reperfusion injury evolves quickly and was thought to be best attenuated by hypothermia induction immediately following return of spontaneous circulation (ROSC). This was supported by animal data which demonstrated that improved neurologic outcome was associated with reduced time to goal temperature following ROSC. More recently this hypothesis has been called into question by 2 clinical trials which suggested that time to initiation of cooling was not associated with improved neurologic outcome at discharge.

There may be another benefit to early therapeutic cooling. Animal data suggest that intra-arrest induction of therapeutic hypothermia (IATH) improves rates of ROSC from cardiac arrest. This is corroborated by a report describing an impressively high ROSC rate of 60.9% among patients receiving IATH. This was a higher frequency of ROSC than reported in similar patient groups. It has been demonstrated that mild hypothermia exerts a stabilizing effect on the myocardium, decreasing the rate of refibrillation following ROSC. Mild hypothermia has also been shown to prolong ventricular refractoriness and repolarization, possibly facilitating electrical defibrillation by slowing repolarization ion currents.

Recently we conducted a retrospective observational study that demonstrated an association between the administration of IATH and ROSC.22 We found that the likelihood of ROSC with IATH was 2.4 (95% CI 1.41-4.24) time higher in the subset of patients who received > 700ml of 4º C normal saline compared to those who did not receive IATH. Our study lacked sufficient power to demonstrate a difference in survival to admission or discharge; however, we noted trends towards improved survival. Current intra-arrest treatments do not obtain ROSC rates greater than those seen in our study with IATH. These associations were noted in all rhythms, including asystole and pulseless electrical activity.

Obtaining ROSC quickly with the resulting decrease in time spent in a low or no flow circulation would have obvious downstream effects on both hospital mortality and neurologic function, independent of the effect of mild hypothermia in the post-arrest inflammatory state. Surprisingly these associations were seen even with fluid volumes that were too low to change core body temperature suggesting that the benefits of therapeutic hypothermia on the myocardium may be possible even at relatively low fluid volumes.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Out-of-Hospital Cardiac Arrest
Drug: 4 degree chilled saline
4 degree chilled saline up to 2L in the prehospital setting
  • Active Comparator: Intra-Arrest Therapeutic Hypothermia
    Intervention: Drug: 4 degree chilled saline
  • Active Comparator: Post-Arrest Therapeutic Hypothermia
    Intervention: Drug: 4 degree chilled saline
Garrett JS, Studnek JR, Blackwell T, Vandeventer S, Pearson DA, Heffner AC, Reades R. The association between intra-arrest therapeutic hypothermia and return of spontaneous circulation among individuals experiencing out of hospital cardiac arrest. Resuscitation. 2011 Jan;82(1):21-5. doi: 10.1016/j.resuscitation.2010.09.473. Epub 2010 Oct 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
363
June 2012
June 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Cardiac arrest of presumed medical etiology in the out-of-hospital setting

Exclusion Criteria:

  • Traumatic Cardiac Arrests
  • Cardiac Arrests Due to hemorrhage
  • Cardiac arrests involving children or young adults
  • Patients presumed to be pregnant
  • Patients with a do not resuscitate
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01413399
MeckHypo2011
Yes
Jonathan Studnek, Carolinas Medical Center
Carolinas Medical Center
Not Provided
Principal Investigator: Jonathan R Studnek, PhD Carolinas Medical Center
Carolinas Medical Center
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP