REmote iSchemic Conditioning in acUtE BRAin INfarction Study (RESCUE-BRAIN)

Lower Limb Ischaemic Per-conditioning in Acute Cerebral Infarction (<H6): Multicenter Randomized Study With Stratification on IV Thrombolysis and PROBE Design (Prospective Randomized Open Trial With Blinded End-Point)

Cerebral infarction is the most common form of stroke (80% of strokes). Stroke is the first cause of acquired disability, and the 2nd cause of dementia and death. The only approved treatment in the first 4.5 hour is intravenous rt-PA thrombolysis (Actilyse ®) whose objective is recanalization of occluded artery and reperfusion of the brain parenchyma. Few patients are treated (1-5%) and they keep disability in 50-60% of cases. This handicap is mainly correlated to the final infarct size. The objective of neuroprotective treatments is to reduce the final size of the cerebral infarction.

The per-conditioning remote ischemic (Per-CID) showed a neuroprotective effect in cerebral ischemia by reducing the final size of cerebral infarction animal models. The per-CID corresponds, in cases of cerebral ischemia, to iterative ischemia realization of a member with a cuff. In humans, the per-CID has shown a cardioprotective effect in a randomized control trial involving 250 patients within 6 first hours of myocardial infarction and candidate for primary angioplasty.

Study Overview

• Status: Unknown
• Conditions: Cerebral Infarction
• Intervention / Treatment: Other: Usual care; Device: Lower limb tourniquet

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Corbeil-Essonne, France, 91100
    • Centre Hospitalier Sud Francilien
  • Créteil, France, 94000
    • Hopital Henri Mondor
  • Le Chesnay, France, 78150
    • Centre Hospitalier de Versailles
  • Nantes, France, 44093
    • CHU de Nantes
  • Paris, France, 75019
    • Fondation Ophtalmologique Adolphe de Rothschild
  • Paris, France, 75013
    • Hôpital Pitié-Salpétrière
  • Paris, France, 78018
    • Hôpital Bichat
  • Strasbourg, France, 67098
    • CHU de Strasbourg
  • Suresnes, France, 92150
    • Hopital Foch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients ≥ 18 years
• Carotid ischemic stroke
• NIHSS score between 5 and 25
• Brain MRI performed within 6 hours from symptoms onset
• Obtaining a written informed consent of the patient or a third party (parent or close), or emergency inclusion process
• Affiliated with a Medicare (or rightful beneficiary)

Exclusion Criteria:

• Presence of a leg ulcer or a bad skin condition in the lower limbs
• History of arterial occlusive disease of the lower limbs
• Sickle cell disease known (risk of vaso-occlusive crisis)
• History of phlebitis in the lower limbs
• History of cerebral infarction older than 3 months
• Participation in another interventional acute phase protocol
• Patients under guardianship
• Pathologies involving life-threatening within 6 months and making it impossible to evaluate to 3 months
• Patient non-self before the ischemic stroke (Rankin Score previous> 2)
• Pregnant Women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: With per-CID protocol; Usual care patients (thrombolysis or not ) with remote ischemic per-conditioning using an electronic tourniquet .	Device: Lower limb tourniquet; Lower limb tourniquet will be put on half thigh. The protocol will include 4 cycles of inflation cuff 110 mm Hg above systolic blood pressure followed by 4 cycles of deflation in between. The total duration of per-CID protocol will be 40 minutes (4 phases of 5 minutes inflations' of and 4 phases of 5 minutes deflations').
Other: Without per-CID protocol; Usual care patients (thrombolysis or not).	Other: Usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain MRI changes of DWI ( Diffusion-Weighted Imaging) brain infarction volume (cc) between baseline (<H6) and day 1 in the 2 groups of patients ( Remote Ischemic Perconditioning and control)	Central lecture of brain MRI, blinded to clinical data, randomisation group and day of MRI realization ( day 0 or day 1) Endpoint criteria: DWI volume d1-d0 (cc) measured by a dedicated software (Neurinfarct) Comparison of DWI volume d1-d0 between the 2 groups ( Per-CID group and control)	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with Modified Rankin Scale (mRS) <2 at 3 months in the 2 groups (PerCID and control)	Percentage of patients with Modified Rankin Scale (mRS) <2 ( i.e. favorable outcome with no disability) at 3 months in the 2 groups (PerCID and control)	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety of remote perconditioning ischemic process	- Rate of lower limb ischemia and deep venous thrombosis in Per CID group	7 days
safety of remote perconditioning ischemic process	Rate of early neurological worsening (NIHSS score (d1- d0) > 4 points) in Per-CID and control group	7 days
safety of remote perconditioning ischemic process	Percentage of hemorrhagic transformation in case of IV thrombolysis in the 2 groups	7 days

Collaborators and Investigators

• Sponsor: Versailles Hospital
• Collaborators: Unité de Recherche Clinique Paris IDF Ouest
• Investigators: Principal Investigator: Fernando PICO, Neurology Department head, Versailles Hospital

Publications and helpful links

General Publications

• Pico F, Lapergue B, Ferrigno M, Rosso C, Meseguer E, Chadenat ML, Bourdain F, Obadia M, Hirel C, Duong DL, Deltour S, Aegerter P, Labreuche J, Cattenoy A, Smadja D, Hosseini H, Guillon B, Wolff V, Samson Y, Cordonnier C, Amarenco P. Effect of In-Hospital Remote Ischemic Perconditioning on Brain Infarction Growth and Clinical Outcomes in Patients With Acute Ischemic Stroke: The RESCUE BRAIN Randomized Clinical Trial. JAMA Neurol. 2020 Jun 1;77(6):725-734. doi: 10.1001/jamaneurol.2020.0326.
• Pico F, Rosso C, Meseguer E, Chadenat ML, Cattenoy A, Aegerter P, Deltour S, Yeung J, Hosseini H, Lambert Y, Smadja D, Samson Y, Amarenco P. A multicenter, randomized trial on neuroprotection with remote ischemic per-conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol. Int J Stroke. 2016 Oct;11(8):938-943. doi: 10.1177/1747493016660098. Epub 2016 Jul 19.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: July 11, 2014
• First Posted (Estimate): July 15, 2014

Study Record Updates

• Last Update Posted (Actual): September 5, 2018
• Last Update Submitted That Met QC Criteria: September 3, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Brain Infarction; Infarction; Cerebral Infarction
• Other Study ID Numbers: P14/01_RESCUE BRAIN; 2014-A00104-43 (Registry Identifier: ID RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED