Trial of Different Hypothermia Temperatures in Patients Recovered From Out-of-hospital Cardiac Arrest

Pilot Randomized Clinical Trial Comparing the Efficacy of Two Different Hypothermia Temperatures for Treatment of Comatose Patients Recovered From an Out-of-hospital Cardiac Arrest

Mild therapeutic hypothermia in the temperature range of 32º - 34ºC. improves survival in patients recovered from a ventricular fibrillation cardiac arrest. The same therapy is suggested with less evidence for asystole as first rhythm after cardiac arrest. The purpose of this study is to determine whether different temperature targets (32º vs 34º) may have different efficacy in the treatment of post-cardiac arrest patients. If successful, this pilot study will eventually form the basis for a larger, multicentric randomized clinical trial.

Study Overview

• Status: Completed
• Conditions: Cardiac Arrest; Non-environmental Hypothermia
• Intervention / Treatment: Procedure: Endovascular Cooling

Detailed Description

Patients admitted consecutively were potentially eligible for the study if they had a witnessed out-off hospital cardiac arrest (OHCA) apparently related to heart disease and an interval of <60 minutes from collapse to return of spontaneous circulation (ROSC). Additional inclusion criteria were:

1. Age >18 years.
2. Initial registered rhythm of a shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia) or asystole.

Exclusion criteria were:

1. Known pregnancy
2. Glasgow Coma Scale score after ROSC >8.
3. Cardiogenic shock (a systolic blood pressure of <80 mm Hg despite inotrope infusion >30 minutes).
4. Other nonshockable rhythms (pulseless electric activity).
5. Terminal illness present before the OHCA.
6. Possible causes of coma other than cardiac arrest (drug overdose, head trauma, or cerebrovascular accident).

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28046
    • Intensive Cardiac Care Unit. Hospital Universitario la Paz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18
• Resuscitated patients from a cardiac arrest with first rhythm of ventricular fibrillation or asystole
• Witnessed cardiac arrest
• Estimated delay between cardiac arrest and advanced resuscitation < 20 min.
• Resuscitation time from first contact to recovery of spontaneous circulation < 60 min.
• Hemodynamic stability (Mean blood pressure [BP] >60 mmHg), with or without inotropic drugs, before randomization
• Glasgow coma score <9 without sedation before randomization

Exclusion Criteria:

• Pregnant women or suspected pregnancy or fertile women without a negative pregnancy test
• Suspected non-cardiac arrest caused coma
• Electrical instability (uncontrollable life-threatening arrhythmias)
• Hemodynamic instability (Mean BP ≤60 mmHg), refractory to volume infusion or inotropic drugs
• Refractory hypoxemia (saturation <85% with FiO2=100%)
• Previous known terminal illness
• Active bleeding or known coagulopathy
• Opposition from patient's family to enter the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 32º Celsius; Endovascular Cooling was set at a target temperature of 32°C	Procedure: Endovascular Cooling; Infusion of <8°C cold saline followed by the implantation of the Icy 9.3F 38-cm catheter (ZOLL Medical Corporation, Chelmsford, MA) placed in the inferior vena cava through a femoral vein connected to the Thermogard XP Temperature Management System (ZOLL Medical Corporation). Cooling was set at a maximum rate with a target temperature of 32°C or 34°C according to randomization.
Active Comparator: 34º Celsius; Endovascular Cooling was set at a target temperature of 32°C	Procedure: Endovascular Cooling; Infusion of <8°C cold saline followed by the implantation of the Icy 9.3F 38-cm catheter (ZOLL Medical Corporation, Chelmsford, MA) placed in the inferior vena cava through a femoral vein connected to the Thermogard XP Temperature Management System (ZOLL Medical Corporation). Cooling was set at a maximum rate with a target temperature of 32°C or 34°C according to randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival free from severe dependence (Barthel index <60)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival at 6 months		6 months
Barthel Index at 6 months		6 months
Life threatening arrhythmias in different hypothermia temperatures	New life-threatening arrhythmias during hypothermia: ventricular fibrillation, sustained (>30 sec.) monomorphic or polymorphic ventricular tachycardia, extreme bradycardia (heart rate <35 bpm. and/or pauses >3 sec.)	48 hours (during hypothermia)
Impact on ventricular function of different hypothermia temperatures	Echocardiographic evaluation of possible impact of different hypothermia temperatures on ventricular diastolic and systolic function	48 hours During hypothermia

Collaborators and Investigators

• Sponsor: Hospital Universitario La Paz
• Investigators: Principal Investigator: Esteban Lopez-de-Sa, MD, FESC, Intensive Cardiac Care Unit. Department of Cardiology. Hospital Universitario La Paz

Publications and helpful links

General Publications

• Lopez-de-Sa E, Rey JR, Armada E, Salinas P, Viana-Tejedor A, Espinosa-Garcia S, Martinez-Moreno M, Corral E, Lopez-Sendon J. Hypothermia in comatose survivors from out-of-hospital cardiac arrest: pilot trial comparing 2 levels of target temperature. Circulation. 2012 Dec 11;126(24):2826-33. doi: 10.1161/CIRCULATIONAHA.112.136408. Epub 2012 Nov 6.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: July 1, 2010
• First Submitted That Met QC Criteria: July 1, 2010
• First Posted (Estimate): July 2, 2010

Study Record Updates

• Last Update Posted (Estimate): December 5, 2012
• Last Update Submitted That Met QC Criteria: December 4, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Cardiac arrest; Out-of-hospital cardiac arrest; Cardiac arrhythmia; Ventricular function; Post-cardiac arrest syndrome; Hypothermia, induced; Disability evaluation; Internal cooling
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Body Temperature Changes; Heart Arrest; Hypothermia; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: Hypothermia_32vs34