Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial

Authors: Rustam Al-Shahi Salman, Martin S. Dennis, Gordon D. Murray, Karen Innes, Jonathan Drever, Lynn Dinsmore, Carol Williams, Philip M. White, William N. Whiteley, Peter A. G. Sandercock, Cathie L. M. Sudlow, David E. Newby, Nikola Sprigg, David J. Werring, the RESTART collaborators

Published in: Trials | Issue 1/2018

Login to get access

Abstract

Background

For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs.

Methods/design

The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study).

Discussion

Final results of RESTART will be analysed and disseminated in 2019.

Trial registration

ISRCTN71907627 (www.​isrctn.​com/​ISRCTN71907627). Prospectively registered on 25 April 2013.
Appendix
Available only for authorised users
Literature
1.
Poon MT, Fonville AF, Al-Shahi Salman R. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2014;85(6):660–7.CrossRefPubMed
2.
Antithrombotic Trialists Collaboration, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60.CrossRef
3.
Aguilar M, Hart R. Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev. 2005;4:CD001925.
4.
Perry LA, Berge E, Bowditch J, Forfang E, Ronning OM, Hankey GJ, Villanueva E, Al-Shahi Salman R. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2017;5:CD012144.PubMed
5.
Biffi A, Halpin A, Towfighi A, Gilson A, Busl K, Rost N, Smith EE, Greenberg MS, Rosand J, Viswanathan A. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2010;75(8):693–8.CrossRefPubMedPubMedCentral
6.
Chong BH, Chan KH, Pong V, Lau KK, Chan YH, Zuo ML, Lui WM, Leung GK, Lau CP, Tse HF, et al. Use of aspirin in Chinese after recovery from primary intracranial haemorrhage. Thromb Haemost. 2012;107(2):241–7.CrossRefPubMed
7.
Flynn RW, MacDonald TM, Murray GD, MacWalter RS, Doney AS. Prescribing antiplatelet medicine and subsequent events after intracerebral hemorrhage. Stroke. 2010;41(11):2606–11.CrossRefPubMed
8.
Teo KC, Lau GK, Mak RH, Leung HY, Chang RS, Tse MY, Lee R, Leung GK, Siu DC, Cheung RT, et al. Antiplatelet resumption after antiplatelet-related intracerebral hemorrhage: a retrospective hospital-based study. World Neurosurg. 2017;106:85–91.CrossRefPubMed
9.
Sung JJ, Lau JY, Ching JY, Wu JC, Lee YT, Chiu PW, Leung VK, Wong VW, Chan FK. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2010;152(1):1–9.CrossRefPubMed
10.
Maxwell AE, MacLeod MJ, Joyson A, Johnson S, Ramadan H, Bellfield R, Byrne A, McGhee C, Rudd A, Price F, et al. Reasons for non-recruitment of eligible patients to a randomised controlled trial of secondary prevention after intracerebral haemorrhage: observational study. Trials. 2017;18(1):162.CrossRefPubMedPubMedCentral
11.
Maxwell AE, Dennis M, Rudd A, Weir CJ, Parker RA, Al-Shahi Salman R. Promoting Recruitment using Information Management Efficiently (PRIME): study protocol for a stepped-wedge cluster randomised controlled trial within the REstart or STop Antithrombotics Randomised Trial (RESTART). Trials. 2017;18(1):22.CrossRefPubMedPubMedCentral
12.
Parker RA, Weir CJ, Maxwell AE, Al-Shahi Salman R. Promoting Recruitment using Information Management Efficiently (PRIME): statistical analysis plan for a stepped wedge cluster randomised trial within the REstart or STop Antithrombotics Randomised Trial (RESTART). Trials. 2017;18(1):94.CrossRefPubMedPubMedCentral
13.
Bruno A, Shah N, Lin C, Close B, Hess DC, Davis K, Baute V, Switzer JA, Waller JL, Nichols FT. Improving modified Rankin Scale assessment with a simplified questionnaire. Stroke. 2010;41(5):1048–50.CrossRefPubMed
14.
Dennis M, Mead G, Doubal F, Graham C. Determining the modified Rankin score after stroke by postal and telephone questionnaires. Stroke. 2012;43(3):851–3.CrossRefPubMed
15.
Bruno A, Akinwuntan AE, Lin C, Close B, Davis K, Baute V, Aryal T, Brooks D, Hess DC, Switzer JA, et al. Simplified modified Rankin Scale questionnaire: reproducibility over the telephone and validation with quality of life. Stroke. 2011;42(8):2276–9.CrossRefPubMed
16.
Sprigg N, Robson K, Bath P, Dineen R, Roberts I, Robinson T, Roffe C, Werring D, Al-Shahi Salman R, Pocock S, et al. Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage: protocol for a randomized, placebo-controlled trial. Int J Stroke. 2016;11(6):683–94.CrossRefPubMed
17.
McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med. 2006;119(8):624–38.CrossRefPubMed
18.
Cordonnier C, Potter GM, Jackson CA, Doubal F, Keir S, Sudlow CL, Wardlaw JM, Al-Shahi Salman R. Improving interrater agreement about brain microbleeds: development of the Brain Observer MicroBleed Scale (BOMBS). Stroke. 2009;40(1):94–9.CrossRefPubMed
19.
Gregoire SM, Chaudhary UJ, Brown MM, Yousry TA, Kallis C, Jager HR, Werring DJ. The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds. Neurology. 2009;73(21):1759–66.CrossRefPubMed
20.
Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O’Brien JT, Barkhof F, Benavente OR, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822–38.CrossRefPubMedPubMedCentral
21.
Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–7.CrossRefPubMedPubMedCentral
22.
Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hrobjartsson A, Schulz KF, Parulekar WR, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.CrossRefPubMedPubMedCentral
23.
Tudur Smith C, Hopkins C, Sydes MR, Woolfall K, Clarke M, Murray G, Williamson P. How should individual participant data (IPD) from publicly funded clinical trials be shared? BMC Med. 2015;13:298.CrossRefPubMedPubMedCentral
Metadata
Title
The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial
Authors
Rustam Al-Shahi Salman
Martin S. Dennis
Gordon D. Murray
Karen Innes
Jonathan Drever
Lynn Dinsmore
Carol Williams
Philip M. White
William N. Whiteley
Peter A. G. Sandercock
Cathie L. M. Sudlow
David E. Newby
Nikola Sprigg
David J. Werring
the RESTART collaborators
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2542-6

Other articles of this Issue 1/2018

Trials 1/2018 Go to the issue

Study protocol

Photodynamic therapy with Bixa orellana extract and LED for the reduction of halitosis: study protocol for a randomized, microbiological and clinical trial

Study protocol

Culturally tailored, peer-based sleep health education and social support to increase obstructive sleep apnea assessment and treatment adherence among a community sample of blacks: study protocol for a randomized controlled trial

Study protocol

Positive end-expiratory pressure (PEEP) level to prevent expiratory flow limitation during cardiac surgery: study protocol for a randomized clinical trial (EFLcore study)

Research

Recruiting care homes to a randomised controlled trial

Study protocol

Feasibility of an online mindfulness-based program for patients with melanoma: study protocol for a randomised controlled trial

Study protocol

TRAnexamic acid in hemorrhagic CESarean section (TRACES) randomized placebo controlled dose-ranging pharmacobiological ancillary trial: study protocol for a randomized controlled trial