Out-of-hospital Cardiac Arrest (OHCA)J-NEURONCT06776549
Hypothermia Versus Normothermia After Extracorporeal Cardiopulmonary Resuscitation for Out-of-hospital Cardiac Arrest
A study of Out-of-hospital Cardiac Arrest (OHCA) and ECMO Treatment, run by Kagawa University at 29 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Out-of-hospital Cardiac Arrest (OHCA), ECMO Treatment, Temperature
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 468 participants
- Where
- 29 sitesJapan
- Study dates
- 6 Jan 2025to 31 Jan 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- OHCA
- Age of 18-75 years, known or estimated
- An initial cardiac arrest rhythm of ventricular fibrillation/pulseless ventricular tachycardia or pulseless electrical activity
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
29 sites in 1 country. Contact the study team or a site near you to ask about taking part.
29 sites in 1 country
Japan29 sites, 29 recruiting
- Recruiting
Oshima Prefectural Hospital
Amami, Kagoshima-ken, 8940015
Kentaro Nakamura
- Not yet recruiting
Asahikawa Medical University Hospital
Asahikawa, Hokkaido, 0788510
Akihito Tampo
- Recruiting
Ebina General Hospital
Ebina, Kanagawa, 2430432
Takahiro Yukawa
- Recruiting
Hitachi General Hospital
Hitachi-shi, Ibaraki, 317-0077
Yuji Takahashi
- Recruiting
Hyogo Prefectural Kakogawa Medical Center
Kakogawa, Hyōgo, 6758555
Atushi Tanaka
- Recruiting
Kagawa University Hospital
Kita-gun, Kagawa-ken, 7610793
Kenya Kawakita
Takuya Taira
- Recruiting
Hyogo Emergency Medical Center
Kobe, Hyōgo, 6510073
Shinichi Ijuin
Takeshi Nishimura
- Recruiting
Kurume University Hospital
Kurume, Fukuoka, 8300011
Maki Otsuka
- Not yet recruiting
Kyoto Second Red Cross Hospital
Kyoto, Kyoto, 6028026
Kenji Kandori
- Recruiting
Okayama University Hospital
Okayama, Okayama-ken, 7008558
Tetsuya Yumoto
- Recruiting
Saitama Red Cross Hospital
Saitama, Saitama, 3308553
Syunichi Kato
- Recruiting
Sapporo Medical University Hospital
Sapporo, Hokkaido, 0608556
Ryuichiro Kakizaki
- Recruiting
Hokkaido University Hospital
Sapporo, Hokkaido, 0608648
Takeshi Wada
- Recruiting
Tohoku University Hospital
Sendai, Miyagi, 9808574
Shigeki Kushimoto
- Recruiting
Sendai Medical Center
Sendai, Miyagi, 9838520
Yu Kawazoe
- Recruiting
Okinawa Prefectural Nanbu Medical Center & Children's Medical Center
Shimajiri-gun, Okinawa, 9011193
Kota Hoshino
- Recruiting
Osaka Saiseikai Senri Hospital
Suita, Osaka, 5650862
Hirotaka Sawano
- Recruiting
St. Luke's International Hospital
Tokyo, 1048560
Shutaro Isokawa
Kasumi Shirasaki
- Recruiting
Institute of Science Tokyo Hospital
Tokyo, 1138519
Wataru Takayama
- Recruiting
Nippon Medical School Hospital
Tokyo, 1138603
Toru Takiguchi
Takuro Hamaguchi
- Recruiting
Tokyo Metropolitan Bokutoh Hospital
Tokyo, 1308575
Kazuhiro Sugiyama
Taichi Kato
- Recruiting
Keio University Hospital
Tokyo, 1608582
Ryo Yamamoto
- Recruiting
Japanese Red Cross Musashino Hospital
Tokyo, 1808610
Manato Watanabe
- Recruiting
Tokyo Metropolitan Tama Medical Center
Tokyo, 1838524
Yuichi Horikoshi
- Recruiting
National Hospital Organization Disaster Medical Center
Tokyo, 1900014
Kazushige Inoue
- Recruiting
Tottori Prefectural Central Hospital
Tottori-shi, Tottori, 6800901
Makoto Kobayashi
- Recruiting
Toyooka Public Hospital
Toyooka, Hyōgo, 6688501
Futoshi Nagashima
- Recruiting
Tsuyama Chuo Hospital
Tsuyama, Okayama-ken, 7080841
Hiroki Maeyama
- Recruiting
Saiseikai Yokohamashi Tobu Hospital
Yokohama, Kanagawa, 2308765
Kosei Omasa
About this study
Official title: Hypothermia Versus Normothermia After Extracorporeal Cardiopulmonary Resuscitation for Out-of-hospital Cardiac Arrest: A Cluster Randomized Trial (SAVE-J NEUROTHERM Trial)
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.
Read the 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.
- Conditions
- Out-of-hospital Cardiac Arrest (OHCA), ECMO Treatment, Temperature, Post Cardiac Arrest Syndrome
- Being tested
- Temperature control
- Keywords
- Cardiac arrest, Out-of-hospital cardiac arrest (OHCA), Extracorporeal cardiopulmonary resuscitation (ECPR), Temperature control, Post cardiac arrest syndrome (PCAS)
- Medical subject headings
- Out-of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome, Heart Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temperature controlProcedure or surgery
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.
Temperature controlProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Normothermia | Active comparator | Temperature control at 36 °C Receives: Procedure: Temperature control |
| Hypothermia | Experimental | Temperature control at 33-34 °C Receives: Procedure: Temperature control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Measured: At discharge (approximately 25 days)
Secondary outcomes (3)
Survival
Measured: At 30 days, 90 days, and 1 year after admission
Neurological function: Cerebral performance categories (CPC)
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
Measured: At discharge (approximately 25 days), 30 days, 90 days, and 1 year after admission
Adverse events
Adverse events during intensive care unit stay (arrhythmia, bleeding, pneumonia, and bacteremia)
Measured: During the intensive care unit stay, an average of 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2025
- Study start6 Jan 2025
- Primary completion31 Jan 2029 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Out-of-hospital Cardiac Arrest (OHCA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 468 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kagawa University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Akihiko Inoue, Kagawa University
- Investigators
- Akihiko Inoue, Principal investigator, Hyogo Emergency Medical CenterYasuhiro Kuroda, Study chair, Kagawa UniversityToru Hifumi, Study chair, Kyorin University School of MedicineTetsuya Sakamoto, Study director, Teikyo UniversityNaoaki Ichihara, Study director, Osaka University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06776549
- Sponsor's protocol ID
- j-neuro
- Acronym
- J-NEURO
- Status last verified
- Aug 2026
- First submitted
- 3 Jan 2025
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypothermia Versus Normothermia After Extracorporeal Cardiopulmonary Resuscitation for Out-of-hospital Cardiac Arrest: A Cluster Randomized Trial (SAVE-J NEUROTHERM Trial)
- ClinicalTrials.gov ID
- NCT06776549
- Acronym / sponsor ID
- J-NEURO / j-neuro
- Conditions
- Out-of-hospital Cardiac Arrest (OHCA), ECMO Treatment, Temperature, Post Cardiac Arrest Syndrome
- Keywords
- Cardiac arrest, Out-of-hospital cardiac arrest (OHCA), Extracorporeal cardiopulmonary resuscitation (ECPR), Temperature control, Post cardiac arrest syndrome (PCAS)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 468 participants (estimated)
- Lead sponsor
- Kagawa UniversityUniversity, hospital or other
- Study start
- 6 Jan 2025 (actual)
- Primary completion
- 31 Jan 2029 (estimated)
- Study completion
- 31 Jan 2030 (estimated)
- First posted
- 15 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normothermia | Active comparator | Procedure: Temperature controlTemperature control at 36 °C |
| Hypothermia | Experimental | Procedure: Temperature controlTemperature control at 33-34 °C |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- OHCA
- Age of 18-75 years, known or estimated
- An initial cardiac arrest rhythm of ventricular fibrillation/pulseless ventricular tachycardia or pulseless electrical activity
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Temperature controlProcedure: 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. | Procedure or surgery | Hypothermia |
| Temperature controlProcedure: 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. | Procedure or surgery | Normothermia |
Primary outcome
Survival
Time frame: At discharge (approximately 25 days)
3 secondary outcomes
Survival
Time frame: At 30 days, 90 days, and 1 year after admission
Neurological function: Cerebral performance categories (CPC)
Time frame: At discharge (approximately 25 days), 30 days, 90 days, and 1 year after admission
Adverse events
Time frame: During the intensive care unit stay, an average of 2 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Akihiko Inoue principal investigator
Hyogo Emergency Medical Center
Yasuhiro Kuroda study chair
Kagawa University
Toru Hifumi study chair
Kyorin University School of Medicine
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Out-of-hospital Cardiac Arrest (OHCA) and ECMO Treatment, run by Kagawa University at 29 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Akihiko Inoue (81-87-981-2392, j-neuro@googlegroups.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: At discharge (approximately 25 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2026.