title: Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): design and statistical analysis plan of the extended follow-up study.
abstract: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up.
  
  
  
  MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up.
  
  
  
  The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness.
  
  
  
  NTR1804 . Registered on 7 May 2009; ISRCTN10888758 . Registered on 24 July 2012 (main MR CLEAN trial); NTR5073 . Registered on 26 February 2015 (extended follow-up study).
authors.affiliation: Department of Neurology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands. l.a.vandenberg@amc.uva.nl.
authors.forename: Lucie A
authors.initials: LA
authors.lastname: van den Berg
authors.affiliation: Clinical Research Unit of the Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Marcel G W
authors.initials: MG
authors.lastname: Dijkgraaf
authors.affiliation: Department of Radiology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Olvert A
authors.initials: OA
authors.lastname: Berkhemer
authors.affiliation: Department of Neurology, Erasmus MC University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Puck S S
authors.initials: PS
authors.lastname: Fransen
authors.affiliation: Department of Neurology, Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: Debbie
authors.initials: D
authors.lastname: Beumer
authors.affiliation: Department of Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Hester
authors.initials: H
authors.lastname: Lingsma
authors.affiliation: Department of Radiology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Charles B M
authors.initials: CB
authors.lastname: Majoie
authors.affiliation: Department of Neurology, Erasmus MC University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Diederik W J
authors.initials: DW
authors.lastname: Dippel
authors.affiliation: Department of Radiology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Aad J
authors.initials: AJ
authors.lastname: van der Lugt
authors.affiliation: Department of Neurology, Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Oostenbrugge
authors.affiliation: Department of Radiology, Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: Wim H
authors.initials: WH
authors.lastname: van Zwam
authors.affiliation: Department of Neurology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Yvo B W E M
authors.initials: YB
authors.lastname: Roos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D002560:Cerebrovascular Circulation; D002985:Clinical Protocols; D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D057510:Endovascular Procedures / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009426:Netherlands; D016016:Proportional Hazards Models; D020127:Recovery of Function; D012107:Research Design; D012307:Risk Factors; D015607:Stents; D020521:Stroke / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D017131:Thrombectomy / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality / Q000706:statistics & numerical data; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality / Q000706:statistics & numerical data; D013997:Time Factors; D016896:Treatment Outcome
keywords: Acute ischemic stroke; Endovascular treatment; Intravenous thrombolysis; Mechanical thrombectomy; Randomized controlled trial