Clinical trial NCT06776549: Hypothermia Versus Normothermia After Extracorporeal Cardiopulmonary Resuscitation for Out-of-hospital Cardiac Arrest
Official title: Hypothermia Versus Normothermia After Extracorporeal Cardiopulmonary Resuscitation for Out-of-hospital Cardiac Arrest: A Cluster Randomized Trial (SAVE-J NEUROTHERM Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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)
Lead sponsor: Kagawa University
Sponsor class: OTHER
First posted: 2025-01-15
Enrollment: 468
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Survival
timeFrame: At discharge (approximately 25 days)
Secondary outcomes:
measure: Survival
timeFrame: At 30 days, 90 days, and 1 year after admission
measure: Neurological function: Cerebral performance categories (CPC)
timeFrame: At discharge (approximately 25 days), 30 days, 90 days, and 1 year after admission
measure: Adverse events
timeFrame: During the intensive care unit stay, an average of 2 weeks
Other outcomes:
Locations:
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Asahikawa
country: Japan
facility: Asahikawa Medical University Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kakogawa
country: Japan
facility: Hyogo Prefectural Kakogawa Medical Center
state: Hyogo
city: Kobe
country: Japan
facility: Hyogo Emergency Medical Center
state: Hyogo
city: Toyooka
country: Japan
facility: Toyooka Public Hospital
state: Hyogo
city: Kita-gun
country: Japan
facility: Kagawa University Hospital
state: Kagawa
city: Amami
country: Japan
facility: Oshima Prefectural Hospital
state: Kagoshima
city: Ebina
country: Japan
facility: Ebina General Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Saiseikai Yokohamashi Tobu Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Sendai
country: Japan
facility: Sendai Medical Center
state: Miyagi
city: Tsuyama
country: Japan
facility: Tsuyama Chuo Hospital
state: Okayama
city: Shimajiri-gun
country: Japan
facility: Okinawa Prefectural Nanbu Medical Center & Children's Medical Center
state: Okinawa
city: Suita
country: Japan
facility: Osaka Saiseikai Senri Hospital
state: Osaka
city: Kyoto
country: Japan
facility: Kyoto Second Red Cross Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Saitama
country: Japan
facility: Saitama Red Cross Hospital
city: Tokyo
country: Japan
facility: St. Luke's International Hospital
city: Tokyo
country: Japan
facility: Institute of Science Tokyo Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Bokutoh Hospital
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Tokyo
country: Japan
facility: Japanese Red Cross Musashino Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Tama Medical Center
city: Tokyo
country: Japan
facility: National Hospital Organization Disaster Medical Center
city: Tottori
country: Japan
facility: Tottori Prefectural Central Hospital
Study officials:
affiliation: Hyogo Emergency Medical Center
name: Akihiko Inoue
role: PRINCIPAL_INVESTIGATOR
affiliation: Kagawa University
name: Yasuhiro Kuroda
role: STUDY_CHAIR
affiliation: St. Luke's International Hospital
name: Toru Hifumi
role: STUDY_CHAIR
affiliation: Teikyo University
name: Tetsuya Sakamoto
role: STUDY_DIRECTOR
affiliation: Osaka University
name: Naoaki Ichihara
role: STUDY_DIRECTOR
References: