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

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...

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Main Authors:	England, Timothy J., Hedstrom, Amanda, O'Sullivan, Saoirse, Donnelly, Richard, Barrett, David A., Sarmad, Sarir, Sprigg, Nikola, Bath, Philip M.W.
Format:	Article
Published:	American Heart Association 2017
Subjects:	stroke post-conditioning biomarker
Online Access:	https://eprints.nottingham.ac.uk/39949/

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author	England, Timothy J. Hedstrom, Amanda O'Sullivan, Saoirse Donnelly, Richard Barrett, David A. Sarmad, Sarir Sprigg, Nikola Bath, Philip M.W.
author_facet	England, Timothy J. Hedstrom, Amanda O'Sullivan, Saoirse Donnelly, Richard Barrett, David A. Sarmad, Sarir Sprigg, Nikola Bath, Philip M.W.
author_sort	England, Timothy J.
building	Nottingham Research Data Repository
collection	Online Access
description	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
first_indexed	2025-11-14T19:40:15Z
format	Article
id	nottingham-39949
institution	University of Nottingham Malaysia Campus
institution_category	Local University
last_indexed	2025-11-14T19:40:15Z
publishDate	2017
publisher	American Heart Association
recordtype	eprints
repository_type	Digital Repository
spelling	nottingham-399492024-08-15T15:22:08Z https://eprints.nottingham.ac.uk/39949/ 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. 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 American Heart Association 2017-03-06 Article PeerReviewed England, Timothy J., Hedstrom, Amanda, O'Sullivan, Saoirse, Donnelly, Richard, Barrett, David A., Sarmad, Sarir, Sprigg, Nikola and Bath, Philip M.W. (2017) Remote Ischaemic Conditioning after Stroke Trial (RECAST): a pilot randomised placebo controlled phase II trial in acute ischaemic stroke (ISRCTN 86672015). Stroke, 48 (3). ISSN 1524-4628 stroke post-conditioning biomarker http://stroke.ahajournals.org/content/early/2017/03/06/STROKEAHA.116.016429 doi:10.1161/STROKEAHA.116.016429 doi:10.1161/STROKEAHA.116.016429
spellingShingle	stroke post-conditioning biomarker England, Timothy J. Hedstrom, Amanda O'Sullivan, Saoirse Donnelly, Richard Barrett, David A. Sarmad, Sarir Sprigg, Nikola Bath, Philip M.W. Remote Ischaemic Conditioning after Stroke Trial (RECAST): a pilot randomised placebo controlled phase II trial in acute ischaemic stroke (ISRCTN 86672015)
title	Remote Ischaemic Conditioning after Stroke Trial (RECAST): a pilot randomised placebo controlled phase II trial in acute ischaemic stroke (ISRCTN 86672015)
title_full	Remote Ischaemic Conditioning after Stroke Trial (RECAST): a pilot randomised placebo controlled phase II trial in acute ischaemic stroke (ISRCTN 86672015)
title_fullStr	Remote Ischaemic Conditioning after Stroke Trial (RECAST): a pilot randomised placebo controlled phase II trial in acute ischaemic stroke (ISRCTN 86672015)
title_full_unstemmed	Remote Ischaemic Conditioning after Stroke Trial (RECAST): a pilot randomised placebo controlled phase II trial in acute ischaemic stroke (ISRCTN 86672015)
title_short	Remote Ischaemic Conditioning after Stroke Trial (RECAST): a pilot randomised placebo controlled phase II trial in acute ischaemic stroke (ISRCTN 86672015)
title_sort	remote ischaemic conditioning after stroke trial (recast): a pilot randomised placebo controlled phase ii trial in acute ischaemic stroke (isrctn 86672015)
topic	stroke post-conditioning biomarker
url	https://eprints.nottingham.ac.uk/39949/ https://eprints.nottingham.ac.uk/39949/ https://eprints.nottingham.ac.uk/39949/

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

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