The RESCUE BRAIN study : Multicenter randomized trial on neuroprotection with lower limb ischaemic per-conditioning in the acute phase of cerebral infarction (<H6) F Pico, E Meseguer, C Rosso, J Yeung, ML Chadenat, A Cattenoy, P Aegerter, D Smadja, H Hosseini, Y Samson, P Amarenco From the Neurology Department and Stroke Center, Versailles Mignot Hospital ( FP, JY, MLC),Versailles, France; Versailles Saint Quentin en Yvelines University, France ( FP); AP-HP, Urgences Cerebro-Vasculaires, Pitie -Salpetriere Hospital, Paris, France ( CR,YS), UPMC, Univ Paris 06, Paris, France ( CR,YS) ; Versailles Delegation à la Recherche Clinique (DRCI)), Mignot Hospital, Le Chesnay, France (AC.), URC PO ( Unité Recherche Clinique Paris Ouest) ( PA), Stroke Center Sud Francilien Hospital, Evry ( DS); Stroke Center Mondor Hospital and School of Medicine,Créteil, France ( HH); ), AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Department of Neurology and Stroke Centre (PA), Paris, France;
Introduction Aim of treatments in the acute phase is to reduce the final size of brain infarction IV Thrombolysis/ Mechanical thombectomy / Neuro protection Handicap is correlated to the final volume ( Zaidi et al. Stroke 2012) Mean Volume of brain saved by alteplase = 24 cm 3 Patients with high blood glucose level have 29 cm 3 larger brain infarction volume than normoglycemic patients ( Rosso al. AJNR 2011)
Neuroprotection STAIR (Stroke Therapy Academic Industry Roundtable) 2009 and STIR (Stroke Imaging Research ) 2013 recommendations 1. Use Brain Infarction Volume as a BIOMARKER Demonstrate that neuroprotective intervention reduce final size of brain infarction in humans. Advantages : a) Same criteria than animal experimentation b) Direct and objective measurement. c) Number of patients needed is quite small (n=100 à 300) and 10 fold less than with clinical endpoint 1. If neuroprotective intervention reduce final volume of BI then a large clinical trial with clinical endpoint ( Rankin) can be considered (n=1000 à 3000).
Objectives To evaluate if remote ischemic Per-Conditionning (per- CID) to a lower limb performed in the first 6 hours of cerebral infarction reduces the growth of the brain infarction
Methodology RESCUE Brain is an interventional, randomized, multicenter trial opened with blinded endpoint assessment (PROBE). Source of funding : PHRC IR 2014-A00104-43 ( Ministry of Health) ClinicalTrials.gov Identifier: NCT02189928 Randomization is stratified on the center and on IV thrombolysis. Mechanical thrombectomy is allowed following IV thrombolysis
Methodology Patients in the intervention group : 4 cycles of inflation cuff 110 mm Hg above systolic blood pressure followed by 4 cycles of deflation between (40 minutes) Main inclusion criteria: patients with carotid brain infarction proven by brain MRI < 6 hours NIHSS score between 5 and 25. Primary Endpoint : Brain MRI changes of DWI brain infarction volume (cc) between baseline (<H6) and day 1 in the 2 groups. Central lecture of brain MRI, blinded to clinical data, using a dedicated and validates software (Neurinfarct ).
Status 42 included patients out of 200 planed (21%)
Ischemic conditioning = transient ischemia without necrosis
Conditionnement ischémique et infarctus cérébral Etude DANOISE Etude RESCUE BRAIN Design Monocentrique Multicentrique Per CID Préhospitalier Avant confirmation diagnostique Intrahospitalier Après l IRM Per CID Bras Membre inférieur non atteint Profil patients Peu grave NIHSS median 4 NIHSS 5-25 Critère de jugement Variation vol IC ( M1) Variation vol IC (J1)
Conditionnement ischémique référence N Pathologie Intervention Resultats Staat et al Circulation 2005 30 IDM <H6 Post CI après ouverture artère 36 % AUC tropo Hausenloy et al 57 Pontages PréCID 4 cycles 5 AUC tropo Lancet 2007 coronaires min/ 5 min Thielmann M et al 329 Pontages PréCID 4 cycles 5 mortalité à M18 et Lancet 2013 coronaires min/ 5 min events CV Hoole et al 244 Coronarographie PréCID 4 cycles 5 AUC tropo Circulation 2009 programmée min/ 5 min events CV Botker et al. Lancet 2010 * 250 IDM < 6h PréCID 4 cycles 5 min/ 5 min En préhospitalier surface IDM en SPECT * RCT Etude CONDI2: 2300, critères cliniques