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Abstract
Objective The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA).
Design Eligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90 min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0–2 at day 90.
Results Ten UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13–21). Median stroke onset to IVT start was 120 min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0–1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0–2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021).
Conclusions The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability-free survival.
Trial registration number NCT01745692; Results.
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Collaborators Trial coordinator: Alicia Murray. Trial Steering Committee (Stroke Association): Gary Ford (chair), Keith Muir, Phil White, Martin M Brown, Andy Clifton, Janet Freeman, Ian Ford; (HTA Phase): Hugh Markus (chair), Joanna Wardlaw. Independent Data Monitoring Committee (Stroke Association): Kennedy Lees, Andy Molyneux, Steff Lewis; (HTA Phase): Tom Robinson, Andy Molyneux, John Norrie. Sites and investigators: University College London Hospital (18)—Fergus Robertson, Richard Perry, Martin M Brown; Newcastle (13)—Anand Dixit, Phil White; St George's, University of London (12)—Geoff Cloud, Andrew Clifton, Jeremy Madigan; University Hospital of N Staffordshire (6)—Christine Roffe, Sanjeev Nayak; Charing Cross Hospital (5)—Kyriakos Lobotesis; Salford Royal Hospital (5)—Craig Smith, Amit Herwadkar; King's College Hospital, London (2)—Naga Kandasamy; Leeds (2)—Tony Goddard, John Bamford; Nottingham (1)—Ganesh Subramanian, Rob Lenthall; QE Hospital Birmingham (1)—Edward Littleton, Sal Lamin. Research coordinators: Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham.
Contributors KWM is guarantor of the data. Site study coordinators and principal investigators (physician and interventionalist) are listed and contributed to data acquisition. Additional data analysis was undertaken by JM and RL. The Statistical Analysis Plan was written by C-MM and IF. Statistical analysis was undertaken by C-MM. The manuscript draft was prepared by KWM and PW with input from all members of the Trial Steering Committee. All authors critically reviewed the manuscript content.
Funding The start-up phase of the trial was funded by grants from the Stroke Association (TSA 2011/2006) from 2012 to 2015 and the National Institute of Health Research (NIHR) Health Technology Assessment programme (HTA 14.08.47) from 2015 to 2016, and received unrestricted grants from Codman and Covidien (Medtronic). MMB's Chair in Stroke Medicine is supported by the Reta Lila Weston Trust for Medical Research. GAF is supported by an NIHR Senior Investigator Award. Recruitment was predominantly undertaken by NIHR Hyperacute Stroke Research Centres. Part of this work was undertaken at University College London and University College Hospital, which received a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centres funding scheme. The Systematic Image Review System 2 used for image adjudication was developed and hosted at the University of Edinburgh. Funding for the trial was obtained from the Stroke Association by KWM, PW, IF and JW and from the HTA by KWM, PW, IF, JW, GAF, MMB and AC.
Disclaimer The funding bodies had no role in the design, conduct or interpretation of the trial.
Competing interests The Trial Steering Committee was chaired by GAF (Stroke Association funded phase) and by H Markus (HTA phase). JF was the lay representative on the Trial Steering Committee and participated in all trial design and management decisions. The Data Monitoring Committee was chaired by K R Lees (Stroke Association phase) and by T Robinson (HTA phase); and included S Lewis (Stroke Association phase), J Norrie (HTA phase) and A Molyneux (throughout).
Ethics approval National Research Ethics Service Committee North East-Newcastle and North Tyneside 2 (12-NE-0315). Scotland A Research Ethics Committee (12/SS/0059).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Reported and additional data have been shared with the HERMES pooling project of stent-retriever trials.