Please use this identifier to cite or link to this item:
Title: The National Institute for Health Research Hyperacute Stroke Research Centres and the ENCHANTED trial: the impact of enhanced research infrastructure on trial metrics and patient outcomes.
Authors: Robinson, TG
Wang, X
Durham, AC
Ford, GA
Liao, J
Littlewood, S
Roffe, C
White, P
Chalmers, J
Anderson, CS
ENCHANTED Investigators
First Published: 13-Feb-2019
Publisher: BMC (part of Springer Nature), World Health Organization (WHO)
Citation: Health Research Policy and Systems, 2019, 17, Article number: 19
Abstract: BACKGROUND: The English National Institute for Health Research Clinical Research Network first established Hyperacute Stroke Research Centres (HSRCs) in 2010 to support multicentre hyperacute (< 9 h) and complex stroke research. We assessed the impact of this investment on research performance and patient outcomes in a post-hoc analysis of country-specific data from a large multicentre clinical trial. METHODS: Comparisons of baseline, outcome and trial metric data were made for participants recruited to the alteplase-dose arm of the international Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) at National Institute for Health Research Clinical Research Network HSRCs and non-HSRCs between June 2012 and October 2015. RESULTS: Among 774 ENCHANTED United Kingdom participants (41% female; mean age 72 years), 502 (64.9%) were recruited from nine HSRCs and 272 (35.1%) from 24 non-HSRCs. HSRCs had higher monthly recruitment rates (median 1.5, interquartile interval 1.4-2.2 vs. 0.7, 0.5-1.3; p = 0.01) and shorter randomisation-to-treatment times (2.6 vs. 3.1 min; p = 0.01) compared to non-HSRCs. HSRC participants were younger and had milder stroke severity, but clinically important between-group differences in 90-day death or disability outcomes remained after adjustment for minimisation criteria and important baseline variables at randomisation, whether defined by ordinal modified Rankin scale score shift (adjusted OR 0.82, 95% CI 0.62-1.08; p = 0.15), scores 2 to 6 (adjusted OR 0.71, 95% CI 0.50-1.01; p = 0.05), or scores 3 to 6 (adjusted OR 0.82, 95% CI 0.57-1.17; p = 0.27). There was no significant difference in symptomatic intracerebral haemorrhage, nor heterogeneity in the comparative treatment effects between low- and standard-dose alteplase by HSRCs or non-HSRCs. CONCLUSIONS: Infrastructure investment in HSRCs was associated with improved research performance metrics, particularly recruitment and time to treatment with clinically important, though not statistically significant, improvements in patient outcomes. TRIAL REGISTRATION: Unique identifier: NCT01422616 .
DOI Link: 10.1186/s12961-019-0417-2
eISSN: 1478-4505
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: The datasets analysed during the current study are available from the corresponding author on reasonable request. Additional files at version of record: Additional file 1: Imaging transfer and analysis, and definitions of symptomatic intracerebral haemorrhage. (DOCX 40 kb) Additional file 2: Table S1. Use of alteplase and management details from randomisation to day 7 by hyperacute stroke research centres (HSRCs) and non-HSRCs. Table S2. Key secondary outcome of symptomatic intracerebral haemorrhage across all definitions by HSRCs and nonHSRCs. Table S3. Key efficacy outcomes by randomised treatment and HSRCs and non-HSRCs. Table S4. Key efficacy outcomes by randomised treatment and HSRCs and non-HSRCs. Table S5. Key safety outcome of symptomatic intracerebral haemorrhage by randomised treatment and HSRCs and non-HSRCs. (DOCX 49 kb)
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

Files in This Item:
File Description SizeFormat 
s12961-019-0417-2.pdfPublished (publisher PDF)576.52 kBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.