Clinical and Economical Interest of Endovascular Cooling in the Management of Cardiac Arrest (ICEREA Study)

Clinical Interest of Endovascular Cooling in the Management of Cardiac Arrest: Impact on Mortality in a Randomized Medico-economical Trial (the ICEREA Study)

According to international guidelines, mild therapeutic hypothermia is recommended for resuscitated patients after cardiac arrest due to ventricular fibrillation. Whether external or internal cooling is superior in terms of prognosis or security remains unknown. The aim of this study is to evaluate in a randomized trial the clinical and economical interests of the endovascular cooling versus the conventional external cooling for the management of hypothermia after cardiac arrest.

Study Overview

• Status: Completed
• Conditions: Heart Arrest; Hypothermia
• Intervention / Treatment: Procedure: Comparison of 2 cooling procedures

Detailed Description

According to international guidelines, mild therapeutic hypothermia is recommended for resuscitated patients after experiencing cardiac arrest from cardiac origin: "unconscious adult patients with spontaneous circulation after cardiac arrest should be cooled to 32-34°C for 12-24 hours when the initial rhythm was ventricular fibrillation" or pulseless ventricular tachycardia. "Such cooling may also be beneficial for other rhythm or in-hospital cardiac arrest".

"External or internal cooling techniques can be used to initiate cooling within minutes to hours". The two main randomized and positive studies dealing with the efficiency of hypothermia after cardiac arrest have used external cooling systems. However, several animal studies documented the importance of initiating hypothermia as soon as possible after cardiac arrest. Intravascular cooling enables more rapid induction of hypothermia compared with external cooling method after brain injury. Although several human studies have also documented that intravascular cooling provides more precise control of core temperature than external methods and although an endovascular method has been used safely in pilot studies in those experiencing hypothermia after cardiac arrest, the superiority of such a cooling on the prognosis after cardiac arrest remains unknown, as well as its cost efficiency.

The aim of this study is to evaluate in a randomized trial the potential clinical and economical interests of the endovascular cooling versus the conventional external cooling for the management of cardiac arrest from cardiac origin. With a clinical primary endpoint (survival without major neurological sequels), this study will also focus on important secondary endpoints, as the burden of nurse work and the economical costs induced by these 2 different methods of cooling.

• Study Type: Interventional
• Enrollment (Actual): 389
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Teaching Lariboisière Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 and 79 years old
• Out-of-hospital cardiac arrest (OH-CA) due to a presumed cardiac etiology
• Delay between OH-CA and return of spontaneous circulation (ROSC) < 60 minutes
• Delay between ROSC and starting cooling < 240 minutes
• Patient not obeying verbal command after ROSC and prior to starting cooling
• Availability of the "CoolGard" device (ALSIUS product)

Exclusion Criteria:

• Do not reanimate order or terminal disease before inclusion
• Known pregnancy
• Clinical hemorrhagic syndrome or known coagulopathy
• Contra-indication to device usage (such as femoral venous access impossible)
• Hypothermia at admission < 30°C
• Etiology of OH-CA thought to be extra-cardiac (trauma, bleeding or anoxia)
• In hospital cardiac arrest
• Refractory shock (need for extra-corporeal life support)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1-2; Comparison of 2 cooling procedures	Procedure: Comparison of 2 cooling procedures; Comparison of 2 cooling procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical interest of endovascular cooling versus conventional external cooling for the management of cardiac arrest from cardiac origin	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Cost/efficiency ratio (endovascular versus conventional cooling)	at 28 days
Evaluation of the paramedical burden of work	at 28 days
Evaluation of the nurse's satisfaction index	at 28 days
Evaluation of treatment costs: global costs and costs within the first 48 hours of hospitalization	at 28 days
Time necessary to reach the target temperature (33°C): mean speed of temperature decrease	at 28 days
deviations of more than 1°C compared with the target temperature during the 24 hours (24H) after reaching that target temperature	at 28 days
mean speed of rewarming	at 28 days
Safety of the method (type of adverse events)	at 28 days
Analysis according to the type and the cause of the cardiac arrest, duration of resuscitation maneuvers, success of coronary angioplasty, number of organ failures (Logistic Organ Dysfunction System [LODS]	at 28 days
Sequential Organ Failure Assessment [SOFA]	at 28 days
and Organ Dysfunctions and/or Infection [ODIN] scores	at 28 days
Simplified Acute Physiology [SAPS II]), duration of Intensive Care Unit (ICU) stay and duration of mechanical ventilation	at 28 days
The efficiency is measured on survival and on better neurological outcome, as defined by CPC 1 or 2 on the Pittsburgh cerebral performance categories (CPC), with an expected 12% improvement of the survival without major sequels at day 28 after inclusion.	at 28 days and 90 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Alsius Corporation; distributed in France by; IST Cardiology (Le Fresne Camilly, France)
• Investigators: Principal Investigator: Frederic BAUD, MD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002 Feb 21;346(8):557-63. doi: 10.1056/NEJMoa003289.
• Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002 Feb 21;346(8):549-56. doi: 10.1056/NEJMoa012689. Erratum In: N Engl J Med 2002 May 30;346(22):1756.
• Nolan JP, Morley PT, Vanden Hoek TL, Hickey RW, Kloeck WG, Billi J, Bottiger BW, Morley PT, Nolan JP, Okada K, Reyes C, Shuster M, Steen PA, Weil MH, Wenzel V, Hickey RW, Carli P, Vanden Hoek TL, Atkins D; International Liaison Committee on Resuscitation. Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. Circulation. 2003 Jul 8;108(1):118-21. doi: 10.1161/01.CIR.0000079019.02601.90. No abstract available.
• International Liaison Committee on Resuscitation. 2005 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Part 4: Advanced life support. Resuscitation. 2005 Nov-Dec;67(2-3):213-47. doi: 10.1016/j.resuscitation.2005.09.018. No abstract available.
• Steinberg GK, Ogilvy CS, Shuer LM, Connolly ES Jr, Solomon RA, Lam A, Kassell NF, Baker CJ, Giannotta SL, Cockroft KM, Bell-Stephens TE, Allgren RL. Comparison of endovascular and surface cooling during unruptured cerebral aneurysm repair. Neurosurgery. 2004 Aug;55(2):307-14; discussion 314-5. doi: 10.1227/01.neu.0000129683.99430.8c.
• Al-Senani FM, Graffagnino C, Grotta JC, Saiki R, Wood D, Chung W, Palmer G, Collins KA. A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard System and Icy catheter following cardiac arrest. Resuscitation. 2004 Aug;62(2):143-50. doi: 10.1016/j.resuscitation.2004.02.016.
• Deye N, Cariou A, Girardie P, Pichon N, Megarbane B, Midez P, Tonnelier JM, Boulain T, Outin H, Delahaye A, Cravoisy A, Mercat A, Blanc P, Santre C, Quintard H, Brivet F, Charpentier J, Garrigue D, Francois B, Quenot JP, Vincent F, Gueugniaud PY, Mira JP, Carli P, Vicaut E, Baud FJ; Clinical and Economical Impact of Endovascular Cooling in the Management of Cardiac Arrest (ICEREA) Study Group. Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest: A Randomized, Controlled Study. Circulation. 2015 Jul 21;132(3):182-93. doi: 10.1161/CIRCULATIONAHA.114.012805. Epub 2015 Jun 19. Erratum In: Circulation. 2016 Feb 23;133(8):e418.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: October 25, 2006
• First Submitted That Met QC Criteria: October 25, 2006
• First Posted (Estimate): October 26, 2006

Study Record Updates

• Last Update Posted (Estimate): December 1, 2009
• Last Update Submitted That Met QC Criteria: November 30, 2009
• Last Verified: July 1, 2007

More Information

Terms related to this study

• Keywords: Humans; Hypothermia; Treatment outcome; Heart arrest; Cardiopulmonary resuscitation; Brain diseases; Hypoxia-ischemia; Cost Benefit Analysis; Prospective study; Comparative study; Hypothermia for; out-of-hospital cardiac arrest; from cardiac origin; successfully resuscitated
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Body Temperature Changes; Heart Arrest; Hypothermia
• Other Study ID Numbers: P051038

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No