RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke

• Published in: Stroke (1970) Vol. 48; no. 5; pp. 1412 - 1415
• Main Authors: England, Timothy J, Hedstrom, Amanda, O’Sullivan, Saoirse, Donnelly, Richard, Barrett, David A, Sarmad, Sarir, Sprigg, Nikola, Bath, Philip M
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.05.2017
• Subjects: Aged; Aged, 80 and over; Brain Ischemia - blood; Brain Ischemia - diagnostic imaging; Brain Ischemia - therapy; Feasibility Studies; Female; Humans; Ischemic Preconditioning - adverse effects; Ischemic Preconditioning - methods; Male; Middle Aged; Outcome Assessment (Health Care); Pilot Projects; Single-Blind Method; Stroke - blood; Stroke - diagnostic imaging; Stroke - therapy; stroke; biomarkers; ischemic conditioning
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.116.016429

BACKGROUND AND PURPOSE—Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. METHODS—We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. RESULTS—Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75–9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group (P=0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5–5) versus 3 (interquartile range, 2–9.5; P=0.04); RIC augmented plasma HSP27 (heat shock protein 27; P<0.05, repeated 2-way ANOVA) and phosphorylated HSP27 (P<0.001) but not plasma S100-β, matrix metalloproteinase-9, endocannabinoids, or arterial compliance. CONCLUSIONS—RIC after acute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. CLINICAL TRIAL REGISTRATION—URLhttp://www.isrctn.com. Unique identifierISRCTN86672015.