Neuroprotective Effect of Remote Ischemic Post-conditioning in Out-of-hospital Cardiac Arrest

Официальное название

Neuroprotective Effect of Remote Ischemic Post-conditioning in Out-of-hospital Cardiac Arrest : a Randomized Open Label Controlled Trial

Обзор

Patients admitted to intensive care unit (ICU) following an out-of-hospital cardiac arrest (OHCA) have a high morbidity and mortality rate, primarily due to ischemia-reperfusion (I/R) syndrome leading to anoxic-ischemic brain injury. Despite current recommended advanced life support therapies, no specific treatment or procedure has yet been shown to improve the neurological outcome of such patients. Remote ischemic post-conditioning (RIPOST) which usually consists of applying brief and repeated cycles of ischemia alternating with reperfusion by inflating and deflating a blood pressure cuff or a pneumatic tourniquet placed around a limb, is a promising strategy to protect organs against I/R injury, including brain. Regarding cardiac arrest, pre-clinical studies have demonstrated an improvement in neurological outcome in animal subjects treated with RIPOST after cardiopulmonary resuscitation. The aim of our study is to demonstrate the benefit of early RIPOST in OHCA patients in reducing neurological injury and organ failure related to I/R syndrome.

Подробное описание

The RIPOST trial is a prospective, single-center, randomized, open-label, parallel group trial.

Patients with inclusion criteria will be randomized in two parallel groups:

* Experimental group: standard of care associated to 3 RIPOST sessions : one within the 4 hours following cardiac arrest, one 12 hours after cardiac arrest and one 24 hours after cardiac arrest. A RIPOST session = four cycles of cuff inflation to 200 mmHg for five minutes and then deflation to 0 mmHg for another five minutes, using an inflatable thigh tourniquet (total duration of the session = 40 minutes). * Control group: standard of care associated to 3 sham sessions at inclusion, 24, and 48 hours after inclusion. A sham session = application of the thigh tourniquet during 40 minutes without any inflation.

Inclusion duration: 36 months

Patient participation duration: 3 months

Study duration: 39 months

Вмешательства

• Другое Remote ischemic post conditioning sessions
  Three sessions of RIPOST (within the 4 hours following cardiac arrest and then 12 and 24 hours after cardiac arrest), as follows: four cycles of cuff inflation to 200 mmHg for 5 min and then deflation to 0 mmHg for another 5 min (40 min total duration of the intervention), using an inflatable thigh tourniquet
• Другое Sham sessions
  Three sessions of a sham procedure (within the 4 hours following cardiac arrest and then 12 and 24 hours after cardiac arrest), as follows : application of a thigh tourniquet during 40 min without any inflation

Первичные конечные точки

• Neurofilament light chain (NFL) blood level evolution between 6 and 72 hours after cardiac arrest occurrence [Срок оценки: 72 hours after out-of-hospital cardiac arrest occurrence]

Вторичные конечные точки (7)

• Sepsis organ failure assessment score (SOFA) [Срок оценки: 72 hours after out-of-hospital cardiac arrest occurrence]
• Rate of patients with NFL peak level >500 pg/mL [Срок оценки: 72 hours after out-of-hospital cardiac arrest occurrence]
• Neuron-specific enolase (NSE) blood level evolution between 6 and 72 hours after cardiac arrest occurrence [Срок оценки: 72 hours after out-of-hospital cardiac arrest occurrence]
• S100B protein (PS100B) blood level evolution between 6 and 72 hours after cardiac arrest occurrence [Срок оценки: 72 hours after out-of-hospital cardiac arrest occurrence]
• ICU mortality rate from multi-organ failure and from neurological injury [Срок оценки: At intensive care unit (ICU) discharge, up to 28 days]
• Modified Rankin Scale (mRS) [Срок оценки: 90 days after out-of-hospital cardiac arrest occurrence]
• Post out-of-hospital cardiac arrest event occurrence [Срок оценки: 24 hours after out-of-hospital cardiac arrest occurrence]

Критерии участия

Критерии включения

• Out-of-hospital cardiac arrest with stable return of spontaneous circulation (ROSC > 20 minutes)
• Patient receiving invasive mechanical ventilation for coma (Glasgow score < 8)
• Availability of a lower limb without intravenous infusion or tension cuff positioned on it
• Randomization and application of the first session of the tested procedure within 4 hours after ROSC
• Consent of a next-of-kin or inclusion in emergency procedure

Критерии исключения

• Age < 18 y.o or pregnancy
• Patient unable to walk without assistance, unable to support himself properly without assistance, bedridden, incontinent and requiring nursing constant attention and care (corresponding to a mRS equal to 4 or 5)
• Interval between cardiac arrest and ROSC (no flow + low flow) estimated > 60 minutes
• Unwitnessed cardiac arrest with asystole as first rhythm
• In-hospital cardiac arrest
• Refractory cardiac arrest (no ROSC considered as stable)
• Cardiac arrest from traumatic, hemorrhage, stroke or hanging supposed origin
• Mean arterial pressure < 65mmHg persisting despite appropriate vascular filling and vasopressor and/or inotropic support
• Active uncontrolled bleeding
• Contraindication or not possible to use a pneumatic tourniquet on none of the two lower limbs (amputations, intravenous infusion positioned on both lower limbs, tourniquet size incompatible with patient morphology)
• Implementation of extracorporeal arteriovenous circulation for refractory cardiac arrest or refractory cardiogenic shock before inclusion
• Patient already included in this study
• Inclusion in another interventional study which purpose is to improve prognosis after a cardiac arrest
• Judicial protection measure
• Patient without French social security

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 · 1 центр

• Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer — Toulon

Публикации

• Ho AFW, Chong J, Ong MEH, Hausenloy DJ. Remote Ischemic Conditioning in Emergency Medicine-Clinical Frontiers and Research Opportunities. Shock. 2020 Mar;53(3):269-276. doi: 10.1097/SHK.0000000000001362. PMID 32045394
• Kloner RA, Shi J, Dai W, Carreno J, Zhao L. Remote Ischemic Conditioning in Acute Myocardial Infarction and Shock States. J Cardiovasc Pharmacol Ther. 2020 Mar;25(2):103-109. doi: 10.1177/1074248419892603. Epub 2019 Dec 11. PMID 31823646
• Albrecht M, Meybohm P, Broch O, Zitta K, Hein M, Grasner JT, Renner J, Bein B, Gruenewald M. Evaluation of remote ischaemic post-conditioning in a pig model of cardiac arrest: A pilot study. Resuscitation. 2015 Aug;93:89-95. doi: 10.1016/j.resuscitation.2015.05.019. Epub 2015 Jun 4. PMID 26051813
• England TJ, Hedstrom A, O'Sullivan SE, Woodhouse L, Jackson B, Sprigg N, Bath PM. Remote Ischemic Conditioning After Stroke Trial 2: A Phase IIb Randomized Controlled Trial in Hyperacute Stroke. J Am Heart Assoc. 2019 Dec 3;8(23):e013572. doi: 10.1161/JAHA.119.013572. Epub 2019 Nov 21. PMID 31747864
• Moseby-Knappe M, Mattsson N, Nielsen N, Zetterberg H, Blennow K, Dankiewicz J, Dragancea I, Friberg H, Lilja G, Insel PS, Rylander C, Westhall E, Kjaergaard J, Wise MP, Hassager C, Kuiper MA, Stammet P, Wanscher MCJ, Wetterslev J, Erlinge D, Horn J, Pellis T, Cronberg T. Serum Neurofilament Light Chain for Prognosis of Outcome After Cardiac Arrest. JAMA Neurol. 2019 Jan 1;76(1):64-71. doi: 10.1001 PMID 30383090

Идентификаторы

NCT: NCT06473207 · 2023-CHITS-010 · 2023-A02457-38

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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