Hypothermia Versus Normothermia After Extracorporeal Cardiopulmonary Resuscitation for Out-of-hospital Cardiac Arrest

Not Applicable

Recruiting

• Conditions: Out-of-hospital Cardiac Arrest (OHCA); ECMO Treatment; Temperature; Post Cardiac Arrest Syndrome

• Registration Number: NCT06776549
• Lead Sponsor: Kagawa University

Brief Summary

The SAVE-J NEUROTHERM trial is a cluster randomized trial that evaluated and compared the mortality risk, neurological outcomes, and adverse events between patients who underwent hypothermia and those who underwent normothermia after extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest.

Detailed Description

Temperature control is a key neurointensive care for post-cardiac arrest patients. Although therapeutic hypothermia has been shown to be effective in the past, recent large randomized controlled trials have failed to demonstrate its efficacy. The international guidelines recommend temperature control under 37.7°C. However, the optimal temperature control, i.e., hypothermia versus normothermia, remains controversial. Additionally, randomized controlled trials that examined temperature control after extracorporeal cardiopulmonary resuscitation (ECPR) are lacking.

ECPR is a resuscitation technique using extracorporeal membrane oxygenation (ECMO) for refractory cardiac arrest. In ECPR patients, ECMO using a heat exchanger can more rapidly achieve the targeted temperature as compared to other temperature control devices. Early cooling to achieve hypothermia after resuscitation is expected to be more effective for neuroprotection in the injured brain. Thus, the investigators hypothesized that hypothermia would be effective in ECPR patients.

Furthermore, ECMO can stabilize the respiratory and circulatory status. Therefore, hypothermia, which may have side effects such as electrolyte abnormalities and arrhythmias, may be safely performed by ECMO. However, ECMO requires the administration of anticoagulants; therefore, it has the risk of hemorrhagic complications. Among patients receiving ECPR, bleeding is a common complication due to its relatively difficult procedure, considering the fact that emergent cannulation is performed under resuscitation. Additionally, CPR-related complications can also result in bleeding. These complications may be enhanced by hypothermia. Therefore, hypothermia after ECPR could contribute to a favorable outcome, but it could also cause bleeding.

The SAVE-J NEUROTHERM trial is a cluster randomized trial that evaluated and compared the mortality risk, neurological outcomes, and adverse events between out-of-hospital cardiac arrest (OHCA) patients who underwent hypothermia and normothermia after ECPR.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2025-01-03
• Study Start: 2025-01-06
• Study First Submitted QC: 2025-01-14
• Study First Posted: 2025-01-15
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-21
• Primary Completion: 2027-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 468

Inclusion Criteria

• OHCA
• Age of 18-75 years, known or estimated
• An initial cardiac arrest rhythm of ventricular fibrillation/pulseless ventricular tachycardia or pulseless electrical activity

Exclusion Criteria

• ECMO initiated after sustained return of spontaneous circulation (ROSC) and patients with sustained ROSC before ECMO initiation
• OHCA of presumed non-cardiac etiology
• Time from emergency call or witnessed arrest to hospital arrival of >60 min
• Time from hospital arrival to ECMO initiation of >60 min
• Pre-hospital ECPR
• Unavailability of the ECMO heat exchanger for temperature control
• Glasgow Coma Scale score before temperature control of >8
• Core body temperature upon hospital arrival of ≤32ºC
• Surgical intervention before temperature control (e.g., surgical intervention for the primary disease or complications related to resuscitation/ECMO procedures)
• Do Not Attempt Resuscitation) order confirmed prior to temperature control
• Limitations in intensive care before temperature control
• Known cerebral performance category (CPC) of 3-4 before cardiac arrest
• Known chronic obstructive pulmonary disease with home oxygen therapy
• Known or suspected pregnancy
• Concomitant illness, such as malignancy, shortens life expectancy (180-day survival unlikely)
• Consent not obtained or withdrawn by the participant or surrogate
• Other reasons, physician's decision not to enroll the patient

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Survival	At discharge (approximately 25 days)

Secondary Outcome Measures

Name	Time	Method
Survival	At 30 days, 90 days, and 1 year after admission
Neurological function: Cerebral performance categories (CPC)	At discharge (approximately 25 days), 30 days, 90 days, and 1 year after admission	The range of cerebral performance category (CPC) score is from 1 (normal/good cerebral function) to 5 (brain death or death). The higher the score, the worse the outcome.; A favorable neurological outcome was defined as a CPC of 1-2, whereas an unfavorable outcome was defined as a CPC of 3-5
Adverse events	During the intensive care unit stay, an average of 2 weeks	Adverse events during intensive care unit stay (arrhythmia, bleeding, pneumonia, and bacteremia)

Trial Locations

Locations (28)

Asahikawa Medical University Hospital; 🇯🇵 Asahikawa, Hokkaido, Japan

Oshima Prefectural Hospital; 🇯🇵 Amami, Kagoshima, Japan

Saiseikai Yokohamashi Tobu Hospital; 🇯🇵 Yokohama, Kanagawa, Japan

Tohoku University Hospital; 🇯🇵 Sendai, Miyagi, Japan

Sendai Medical Center; 🇯🇵 Sendai, Miyagi, Japan

Kurume University Hospital; 🇯🇵 Kurume, Fukuoka, Japan

Hyogo Emergency Medical Center; 🇯🇵 Kobe, Hyogo, Japan

Toyooka Public Hospital; 🇯🇵 Toyooka, Hyogo, Japan

Ebina General Hospital; 🇯🇵 Ebina, Kanagawa, Japan

Sapporo Medical University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Hokkaido University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Hyogo Prefectural Kakogawa Medical Center; 🇯🇵 Kakogawa, Hyogo, Japan

Kagawa University Hospital; 🇯🇵 Kita-gun, Kagawa, Japan

Tsuyama Chuo Hospital; 🇯🇵 Tsuyama, Okayama, Japan

Okinawa Prefectural Nanbu Medical Center & Children's Medical Center; 🇯🇵 Shimajiri-gun, Okinawa, Japan

Osaka Saiseikai Senri Hospital; 🇯🇵 Suita, Osaka, Japan

Kyoto Second Red Cross Hospital; 🇯🇵 Kyoto, Japan

Okayama University Hospital; 🇯🇵 Okayama, Japan

Saitama Red Cross Hospital; 🇯🇵 Saitama, Japan

St. Luke's International Hospital; 🇯🇵 Tokyo, Japan

Institute of Science Tokyo Hospital; 🇯🇵 Tokyo, Japan

Nippon Medical School Hospital; 🇯🇵 Tokyo, Japan

Tokyo Metropolitan Bokutoh Hospital; 🇯🇵 Tokyo, Japan

Keio University Hospital; 🇯🇵 Tokyo, Japan

Japanese Red Cross Musashino Hospital; 🇯🇵 Tokyo, Japan

Tokyo Metropolitan Tama Medical Center; 🇯🇵 Tokyo, Japan

National Hospital Organization Disaster Medical Center; 🇯🇵 Tokyo, Japan

Tottori Prefectural Central Hospital; 🇯🇵 Tottori, Japan