Targeted Temperature Management at 33°C Versus Controlled Normothermia for In-hospital Cardiac Arrest

Обзор

The IH-TTM trial is designed to determine whether survival with a favorable neurological outcome is improved by induced hypothermia at 33°C in comatose critically ill patients admitted after resuscitated in-hospital cardiac arrest (IHCA). Recent evidence suggests that targeted temperature management (TTM) at 33°C may provide no survival benefits compared to controlled normothermia in unselected patients with out-of-hospital cardiac arrest (OHCA). However, this evidence is relevant only to OHCA of presumed cardiac origin, chiefly witnessed and immediately followed by resuscitation efforts. Only scant data are available for cardiac arrest (CA) of other origins and for IHCA. In a randomized clinical trial of patients with CA in an initial non-shockable rhythm, the subgroup with IHCA had significantly better outcomes when treated with TTM at 33°C versus controlled normothermia; nevertheless, the sample size was limited. Another randomized controlled trial done specifically in patients with IHCA failed to show benefits of TTM at 33°C compared to controlled normothermia but was underpowered. Thus, whether therapeutic hypothermia is indicated after IHCA remains unclear. IH-TTM will be the largest trial assessing TTM after IHCA.

Вмешательства

• Другое Induced hypothermia at 33°C
  Cooling and maintenance phase : The aim is to achieve the target temperature of 33±0.5°C within 60 minutes after randomization. The target temperature of 33±0.5°C and device setting of 33°C will be maintained until 28 hours after randomization. \- Rewarming: Normothermia will be restored by gradual rewarming at a rate of 0.2°C/h. \- After rewarming: After 40 hours, in those participants who are still comatose or sedated, normothermia (36.5-37.7°C) will be maintained until 72 hours after rando
• Другое Control normothermia
  Participants whose initial temperature is below 33°C may be actively rewarmed to 36.5°-37.7°C, at which point active rewarming will be stopped and passive rewarming performed according to the latest guidelines. Participants whose initial temperature is above 33°C will not be actively rewarmed to normothermia. The goal will be to maintain temperature no higher than 37.8°C. After 40 hours, in those participants who are still comatose or sedated, normothermia (36.5-37.7°C) will be maintained until

Первичные конечные точки

• To assess whether induced hypothermia (TTM at 33°C) is superior to targeted normothermia in providing a favorable neurological outcome, defined as a modified Rankin Scale (mRS) score of 0 to 3 at 6 months. [Срок оценки: 6 months after randomization]

Вторичные конечные точки (12)

• All-cause mortality 2 months after randomization [Срок оценки: 2 months after randomization]
• All-cause mortality 3 months after randomization [Срок оценки: 3 months after randomization]
• All-cause mortality 4 months after randomization [Срок оценки: 4 months after randomization]
• All-cause mortality 6 months after randomization [Срок оценки: 6 months after randomization]
• ICU lengths of stay [Срок оценки: from day of randomization until the day of discharge from ICU, an average of 20 days.]
• Hospital lengths stay [Срок оценки: from day of randomization until the day of discharge from hospital, an average of 20 days.]
• Neurological outcome measured by modified Rankin Scale (mRS) score, ranging from 0 to 6 at 2 months after randomization [Срок оценки: 2 months after randomization]
• Neurological outcome measured by modified Rankin Scale (mRS) score, ranging from 0 to 6 at 3 months after randomization [Срок оценки: 3 months after randomization]
• Neurological outcome measured by modified Rankin Scale (mRS) score ranging from 0 to 6 at 4 months after randomization [Срок оценки: 4 months after randomization]
• Mechanical ventilation duration [Срок оценки: from time of randomization to final extubation or up to 28 days]
• Biomarkers concentration : neuron-specific enolase (NSE) on day 0 [Срок оценки: at day 0]
• Biomarkers concentration : neuron-specific enolase (NSE) on day 2 [Срок оценки: at day 2]

Критерии участия

Критерии включения

• IHCA (unwitnessed IHCA with initial asystole; these patients may still be eligible if visible or audible signs of life were witnessed within 10 minutes after IHCA (no-flow duration ≤10 minutes, in keeping with the non-inclusion criteria for HYPERION study).
• Sustained ROSC (Return Of Spontaneous Circulation) defined as signs of circulation for 20 minutes without chest compressions
• At least 1 mg of epinephrine
• Coma defined as an inability to obey verbal commands (Glasgow Coma Scale motor response <6 or Full Outline of UnResponsiveness (FOUR) score motor response <4) after sustained ROSC
• Eligible for intensive care without restrictions or limitations
• Inclusion within 90 minutes of ROSC
• Age 18 years or older
• Next of kin informed about the trial and having consented to participation of the patient in the trial (patients with coma are unable to consent). If no next of kin can be contacted during screening for the study, trial inclusion will be completed as an emergency procedure by the ICU physician, in compliance with Country of inclusion law.
• Healthcare costs covered by the French statutory healthcare insurance system

Критерии исключения

• Temperature at admission <30°C
• Obvious or suspected pregnancy
• Intracranial bleeding
• Dependent on others for activities of daily living before hospitalization
• Patient under curators, guardianship or under protection of justice
• Correctional facility inmate
• Patient who does no speak French

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 26 центров

• CH d'Angoulême — Angoulême
• CH Dubois Brive — Brive-la-Gaillarde
• CHU de Caen — Caen
• Hôpital Simone Veil — Cannes
• CH Public du Cotentin — Cherbourg
• CHU Clermont-Ferrand — Clermont-Ferrand
• CHU Bocage — Dijon
• CHD Vendée — La Roche-sur-Yon
• … и ещё 18 центров

Бельгия · 5 центров

• Hôpital Erasme — Brussels
• CHU Charleroi — Charleroi
• Hôpital Universitaire de Gand — Ghent
• Hôpital Universitaire de Bruxelles — Jette
• Clinique Saint-PIerre — Ottignies

Guadeloupe · 1 центр

• CHU Les Abymes — Pointe-à-Pitre

Идентификаторы

NCT: NCT07086703 · RC23_0488

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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