Remote Ischaemic Conditioning after Stroke Trial (RECAST): a pilot randomised placebo controlled phase II trial in acute ischaemic stroke (ISRCTN 86672015)

England, Timothy J.; Hedstrom, Amanda; O'Sullivan, Saoirse; Donnelly, Richard; Barrett, David A.; Sarmad, Sarir; Sprigg, Nikola; Bath, Philip M.W.

Abstract

Background:
Repeated episodes of limb ischaemia and reperfusion (remote ischaemic conditioning, RIC) may improve outcome after acute stroke.
Methods:
We performed a pilot blinded placebo-controlled trial in patients with acute ischaemic stroke, randomised 1:1 to receive four 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 haemodynamic measures.
Findings:
Twenty-six patients (13 RIC, 13 sham) were recruited 15.8 hours (SD 6.2) post onset, age 76·2 years (10.5), blood pressure 159/83mmHg (25/11) and NIHSS 5 [IQR 3.75-9.25]. RIC was well tolerated with 49/52 cycles completed in full. Three patients experienced vascular events in the sham group: two ischaemic strokes and two myocardial infarcts versus none in the RIC group (p=0·076, log-rank test). Compared to sham, there was a significant decrease in day 90 NIHSS in the RIC group, median NIHSS 1 [0.5-5] versus 3 [2-9.5], p=0.04; RIC augmented plasma heat shock protein (HSP) 27 (p<0·05, repeated 2-way ANOVA) and phosphorylated HSP27 (p<0·001) but not plasma S100-beta, matrix metalloprotinase-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-URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015

Citation

England, T. J., Hedstrom, A., O'Sullivan, S., Donnelly, R., Barrett, D. A., Sarmad, S., Sprigg, N., & Bath, P. M. (2017). Remote Ischaemic Conditioning after Stroke Trial (RECAST): a pilot randomised placebo controlled phase II trial in acute ischaemic stroke (ISRCTN 86672015). Stroke, 48(5), https://doi.org/10.1161/STROKEAHA.116.016429

• Journal Article Type: Article
• Acceptance Date: Jan 17, 2017
• Online Publication Date: Mar 6, 2017
• Publication Date: May 31, 2017
• Deposit Date: Jan 19, 2017
• Publicly Available Date: Mar 6, 2017
• Journal: Stroke
• Print ISSN: 0039-2499
• Electronic ISSN: 1524-4628
• Publisher: American Heart Association
• Peer Reviewed: Peer Reviewed
• Volume: 48
• Issue: 5
• DOI: https://doi.org/10.1161/STROKEAHA.116.016429
• Keywords: stroke, post-conditioning, biomarker
• Public URL: https://nottingham-repository.worktribe.com/output/849019
• Publisher URL: http://stroke.ahajournals.org/content/early/2017/03/06/STROKEAHA.116.016429
• Contract Date: Jan 19, 2017