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

NCT ID: NCT06776549

Last Updated: 2025-06-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

468 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-06

Study Completion Date

2028-12-31

Brief Summary

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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

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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.

Conditions

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Out-of-hospital Cardiac Arrest (OHCA) ECMO Treatment Temperature Post Cardiac Arrest Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Normothermia

Temperature control at 36 °C

Group Type ACTIVE_COMPARATOR

Temperature control

Intervention Type PROCEDURE

Procedure: Temperature control at 36 °C In the normothermia group receiving ECPR, the temperature of 36ºC will be immediately reached with ECMO using a heat exchanger. After reaching this targeted temperature, the maintenance phase will start, and the target temperature will be maintained at 36ºC. The maintenance phase will end 24 h after reaching this targeted temperature. Then, rewarming to 36ºC-37ºC will be conducted in 24 h. After the rewarming, the temperature will be kept in the range of 36ºC-37.5ºC for 24 h after rewarming or until the end of ECMO, and should not exceed 37.5ºC. Other interventions, such as sedation, administration of neuromuscular blocking agents, antipyretics, and catecholamines, as well as mechanical circulatory support, are optional and performed at the patient's discretion.

Hypothermia

Temperature control at 33-34 °C

Group Type EXPERIMENTAL

Temperature control

Intervention Type PROCEDURE

Procedure: Temperature control at 33-34 °C In the hypothermia group, patients receiving ECPR will be immediately cooled to 33ºC-34ºC with ECMO using a heat exchanger. After reaching this targeted temperature, the maintenance phase will start, and the target temperature will be kept at 33ºC-34°C. The maintenance phase will end 24 h after reaching this targeted temperature. Subsequently, rewarming to 36ºC-37ºC will be conducted in 24 h. After the rewarming, the temperature will be kept in the range of 36ºC-37.5ºC for 24 h after rewarming or until the end of ECMO, and should not exceed 37.5ºC. Other interventions, such as sedation, administration of neuromuscular blocking agents, antipyretics, and catecholamines, as well as mechanical circulatory support, are optional and performed at the patient's discretion.

Interventions

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Temperature control

Procedure: Temperature control at 33-34 °C In the hypothermia group, patients receiving ECPR will be immediately cooled to 33ºC-34ºC with ECMO using a heat exchanger. After reaching this targeted temperature, the maintenance phase will start, and the target temperature will be kept at 33ºC-34°C. The maintenance phase will end 24 h after reaching this targeted temperature. Subsequently, rewarming to 36ºC-37ºC will be conducted in 24 h. After the rewarming, the temperature will be kept in the range of 36ºC-37.5ºC for 24 h after rewarming or until the end of ECMO, and should not exceed 37.5ºC. Other interventions, such as sedation, administration of neuromuscular blocking agents, antipyretics, and catecholamines, as well as mechanical circulatory support, are optional and performed at the patient's discretion.

Intervention Type PROCEDURE

Temperature control

Procedure: Temperature control at 36 °C In the normothermia group receiving ECPR, the temperature of 36ºC will be immediately reached with ECMO using a heat exchanger. After reaching this targeted temperature, the maintenance phase will start, and the target temperature will be maintained at 36ºC. The maintenance phase will end 24 h after reaching this targeted temperature. Then, rewarming to 36ºC-37ºC will be conducted in 24 h. After the rewarming, the temperature will be kept in the range of 36ºC-37.5ºC for 24 h after rewarming or until the end of ECMO, and should not exceed 37.5ºC. Other interventions, such as sedation, administration of neuromuscular blocking agents, antipyretics, and catecholamines, as well as mechanical circulatory support, are optional and performed at the patient's discretion.

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kagawa University

OTHER

Sponsor Role lead

Responsible Party

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Akihiko Inoue

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Akihiko Inoue

Role: PRINCIPAL_INVESTIGATOR

Hyogo Emergency Medical Center

Yasuhiro Kuroda

Role: STUDY_CHAIR

Kagawa University

Toru Hifumi

Role: STUDY_CHAIR

Kyorin University School of Medicine

Tetsuya Sakamoto

Role: STUDY_DIRECTOR

Teikyo University

Naoaki Ichihara

Role: STUDY_DIRECTOR

Osaka University

Locations

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Kurume University Hospital

Kurume, Fukuoka, Japan

Site Status RECRUITING

Asahikawa Medical University Hospital

Asahikawa, Hokkaido, Japan

Site Status NOT_YET_RECRUITING

Sapporo Medical University Hospital

Sapporo, Hokkaido, Japan

Site Status RECRUITING

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Site Status RECRUITING

Hyogo Prefectural Kakogawa Medical Center

Kakogawa, Hyōgo, Japan

Site Status RECRUITING

Hyogo Emergency Medical Center

Kobe, Hyōgo, Japan

Site Status RECRUITING

Toyooka Public Hospital

Toyooka, Hyōgo, Japan

Site Status RECRUITING

Kagawa University Hospital

Kita-gun, Kagawa-ken, Japan

Site Status RECRUITING

Oshima Prefectural Hospital

Amami, Kagoshima-ken, Japan

Site Status RECRUITING

Ebina General Hospital

Ebina, Kanagawa, Japan

Site Status RECRUITING

Saiseikai Yokohamashi Tobu Hospital

Yokohama, Kanagawa, Japan

Site Status RECRUITING

Kyoto Second Red Cross Hospital

Kyoto, Kyoto, Japan

Site Status NOT_YET_RECRUITING

Tohoku University Hospital

Sendai, Miyagi, Japan

Site Status RECRUITING

Sendai Medical Center

Sendai, Miyagi, Japan

Site Status RECRUITING

Okayama University Hospital

Okayama, Okayama-ken, Japan

Site Status RECRUITING

Tsuyama Chuo Hospital

Tsuyama, Okayama-ken, Japan

Site Status RECRUITING

Okinawa Prefectural Nanbu Medical Center & Children's Medical Center

Shimajiri-gun, Okinawa, Japan

Site Status RECRUITING

Osaka Saiseikai Senri Hospital

Suita, Osaka, Japan

Site Status RECRUITING

Saitama Red Cross Hospital

Saitama, Saitama, Japan

Site Status RECRUITING

Tottori Prefectural Central Hospital

Tottori-shi, Tottori, Japan

Site Status RECRUITING

St. Luke's International Hospital

Tokyo, , Japan

Site Status RECRUITING

Institute of Science Tokyo Hospital

Tokyo, , Japan

Site Status RECRUITING

Nippon Medical School Hospital

Tokyo, , Japan

Site Status RECRUITING

Tokyo Metropolitan Bokutoh Hospital

Tokyo, , Japan

Site Status RECRUITING

Keio University Hospital

Tokyo, , Japan

Site Status RECRUITING

Japanese Red Cross Musashino Hospital

Tokyo, , Japan

Site Status RECRUITING

Tokyo Metropolitan Tama Medical Center

Tokyo, , Japan

Site Status RECRUITING

National Hospital Organization Disaster Medical Center

Tokyo, , Japan

Site Status RECRUITING

Countries

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Japan

Central Contacts

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Akihiko Inoue

Role: CONTACT

81-87-981-2392

Other Identifiers

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j-neuro

Identifier Type: -

Identifier Source: org_study_id

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