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

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 .

Keywords: Acute ischaemic stroke; alteplase; clinical trials; symptomatic intracerebral haemorrhage; thrombolysis.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the appropriate ethics committee at each participating centre, and written informed consent was obtained from the patient or an appropriate surrogate.

Consent for publication

Not applicable.

Competing interests

TGR is an NIHR Senior Investigator; PW reports institutional research grants from Microvention Terumo, advisory panel fees from Stryker, and educational consulting fees from Microvention; JC reports research grants and lecture fees from Servier; CSA reports advisory panel fees from Amgen, speaking fees from Takeda China, research grants from Takeda China and NHMRC, and holds a Senior Principle Research Fellowship of the NHMRC.

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