Targeted Hypothermia Versus Targeted Normothermia After Convulsive Refractory Status Epilepticus

NCT07383779

The HYBERNATUS-II study is a phase-III, open-label, randomized controlled trial in patients with convulsive refractory SE receiving mechanical ventilation. Patients are allocated at random to either early targeted hypothermia for 24 hours or targeted normothermia at the acute phase of ICU management. This trial is a superiority multicentric trial and patients will be randomized in a 1:1 ratio using an electronic Cas Report Form. Before any examination or intervention related to the study may be carried out, the investigator must obtain the freely given, informed and written consent of the participant, or of his/her substitute decision maker (family member, close relative or legal representative) where applicable. However, eligible subjects are unconscious and inherently not able to consent. Two situations of inclusion are therefore envisaged: \- In case a substitute decision maker is present or contactable: a freely given, informed and written consent of the substitute decision maker will be performed. \- In case a substitute decision maker is not present or contactable in the inclusion time frame, the patient may be included through a process of differed consent. Substitute decision maker will be informed as soon as possible and a freely given, informed and written pursuit consent will be performed. In all cases, the patient will have to confirm his participation to the study through a freely given, informed and written pursuit consent as soon as their condition allows it. If the patient is under curatorship, the pursuit consent may be given based on his or her own decision. If the patient is under guardianship, the written guardian's consent will also be required. Individuals liable to participate in studies stipulated in line 1° of article L. 1121-1 of the Code de la Santé Publique (French Public Health Code) benefit from a preliminary medical examination adapted to the study. Patients will be included after informed consent as soon as possible once they satisfied all eligibility criteria. The inclusion window is until 3.5 hours (210 minutes) after convulsive SE onset. Consecutive eligible patients will be included and randomly allocated in a 1:1 ratio to one of the two procedure groups. Randomization and concealment will be ensured by using a secure, computer-generated, interactive, response system accessible via the Internet available at each study centre 24H/24. Randomization list will be prepared by an independent statistician who will not be in charge of the analysis. Randomization lists will be generated by a dedicated computer program, with randomly varying sized blocks, and stratified as follows: according to sites, previous history of epilepsy \[yes or not\], and results of brain imaging \[Abnormal Brain Imaging or not\]. Each investigator will be able to access the randomization site using a personal password. Randomization will be carried out after checking of the inclusion criteria and the absence of exclusion criteria and after obtaining a written and informed consent or according to the emergency procedure by the principal investigator or a physician representing the investigator before the person is enrolled in the study of each centre involved in the study. Each patient will be assigned a unique identification number. An inclusion confirmation will be sent by email to the investigator specifying the allocated procedure arm. Patients will be randomly allocated to one of the two study procedure groups. The two groups will differ only in the administration of early targeted hypothermia for 24 hours or targeted normothermia at the acute phase of ICU management. All other treatment will be standardized in the two groups. Targeted Hypothermia group : Implementation of allocation arm is started within 30 min after randomization.The objective is to lower the core body temperature to 33°C \[32-34°C\] rapidly after randomization then to maintain this temperature for 24 hours. The management in the targeted hypothermia group will include the following. Targeted normothermia group. Implementation of allocation arm is started within 30 min after randomization. The objective of the control group is to ensure normothermia 37° \[36.5-37.5°C\] for 72 hours after randomization. Antipyretic treatments will be given in case of a core temperature higher than 37.8°C. In case of failure, cooling with a surface non-invasive loop-feedback TTM device associating pads directly adhering to the patient's skin (Artic Sun TM provided by the study, similar in all participating centers) will be initiated with a target temperature of 37° \[36.5-37.5°C\]. No active warming will be provided for patients in the normothermia group who had a spontaneous body temperature below 36.5°C. Patients included in the study will be followed until the 90th day after inclusion. The duration of the participation will therefore be 3 months for each patient.