TY - JOUR
T1 - MR CLEAN-LATE, a multicenter randomized clinical trial of endovascular treatment of acute ischemic stroke in The Netherlands for late arrivals: study protocol for a randomized controlled trial
AU - Fransen, Puck S. S.
AU - Beumer, Debbie
AU - Berkhemer, Olvert A.
AU - van den Berg, Lucie A.
AU - Lingsma, Hester
AU - van der Lugt, Aad
AU - van Zwam, Wim H.
AU - van Oostenbrugge, Robert J.
AU - Roos, Yvo B. W. E. M.
AU - Majoie, Charles B.
AU - Dippel, Diederik W. J.
AU - AUTHOR GROUP
AU - Dippel, Diederik W.
AU - Brouwer, Patrick A.
AU - Boiten, Jelis
AU - Lycklama à Nijeholt, Geert J.
AU - Wermer, Marieke J.
AU - van Walderveen, Marianne A.
AU - Kappelle, L. Jaap
AU - Lo, Rob T.
AU - van Dijk, Ewoud J.
AU - de Vries, Joost
AU - Schonewille, Wouter J.
AU - Vos, Jan Albert
AU - Hofmeijer, Jeannette
AU - van Oostayen, Jacques A.
AU - Vroomen, Patrick C.
AU - Eshghi, Omid
AU - de Kort, Paul L.
AU - van Rooij, Willem Jan
AU - Keizer, Koos
AU - Tielbeek, Xander
AU - de Bruijn, Bas F.
AU - van Dijk, Lukas C.
AU - van den Bergh, J. S. Peter
AU - van Hasselt, Boudewijn A.
AU - Aerden, Leo A.
AU - Dallinga, René J.
AU - Schreuder, Tobien H.
AU - Heijboer, Roel J.
AU - den Hertog, Heleen M.
AU - Gerrits, Dick G.
AU - Visser, Marieke C.
AU - Bot, Joost C.
AU - Marquering, Henk A.
AU - Beenen, Ludo F.
AU - Sprengers, Marieke E.
AU - Jenniskens, Sjoerd
AU - van den Berg, René
AU - Yoo, Albert J.
AU - Koudstaal, Peter J.
N1 - Funding Information: MR CLEAN-LATE is part of the COnsortium for New TReatments of Acute STroke (CONTRAST: Additional file : Appendix 1) and will be coordinated from the Maastricht University Medical Center (see Additional file : Appendix 2 for the MR CLEAN-LATE trial investigators). CONTRAST is supported by the Netherlands Cardiovascular Research Initiative which is supported by the Dutch Heart Foundation (CVON2015-01: CONTRAST), the Brain Foundation Netherlands (HA2015.01.06), and Health~Holland, Top Sector Life Sciences & Health (LSHM17016), Medtronic and Cerenovus. The cost-effectiveness analysis is supported by ZonMW. Funding Information: We acknowledge the support of the Netherlands Cardiovascular Research Initiative which is supported by the Dutch Heart Foundation (CVON2015-01: CONTRAST), the support of the Brain Foundation Netherlands (HA2015.01.06), and the support of Health~Holland, Top Sector Life Sciences & Health (LSHM17016), of Medtronic and Cerenovus. Funding Information: WvZ reports that Maastricht University Medical Center received compensation from Stryker® and Cerenovus® for consultations by WvZ. CM reports that Amsterdam UMC received research grants from CVON/Dutch Heart Foundation, European Commission, TWIN Foundation, and Stryker®; he is a shareholder of Nico-Lab. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background: Endovascular therapy (EVT) for acute ischemic stroke due to proximal occlusion of the anterior intracranial circulation, started within 6 h from symptom onset, has been proven safe and effective. Recently, EVT has been proven effective beyond the 6-h time window in a highly selected population using CT perfusion or MR diffusion. Unfortunately, these imaging modalities are not available in every hospital, and strict selection criteria might exclude patients who could still benefit from EVT. The presence of collaterals on CT angiography (CTA) may offer a more pragmatic imaging criterion that predicts possible benefit from EVT beyond 6 h from time last known well. The aim of this study is to assess the safety and efficacy of EVT for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow. Methods: The MR CLEAN-LATE trial is a multicenter, randomized, open-label, blinded endpoint trial, aiming to enroll 500 patients. We will investigate the efficacy of EVT between 6 and 24 h from time last known well in acute ischemic stroke due to a proximal intracranial anterior circulation occlusion confirmed by CTA or MRA. Patients with any collateral flow (poor, moderate, or good collaterals) on CTA will be included. The inclusion of poor collateral status will be restricted to a maximum of 100 patients. In line with the current Dutch guidelines, patients who fulfill the characteristics of included patients in DAWN and DEFUSE 3 will be excluded as they are eligible for EVT as standard care. The primary endpoint is functional outcome at 90 days, assessed with the modified Rankin Scale (mRS) score. Treatment effect will be estimated with ordinal logistic regression (shift analysis) on the mRS at 90 days. Secondary endpoints include clinical stroke severity at 24 h and 5–7 days assessed by the NIHSS, symptomatic intracranial hemorrhage, recanalization at 24 h, follow-up infarct size, and mortality at 90 days, Discussion: This study will provide insight into whether EVT is safe and effective for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow on CTA. Trial registration: NL58246.078.17, ISRCTN19922220, Registered on 11 December 2017
AB - Background: Endovascular therapy (EVT) for acute ischemic stroke due to proximal occlusion of the anterior intracranial circulation, started within 6 h from symptom onset, has been proven safe and effective. Recently, EVT has been proven effective beyond the 6-h time window in a highly selected population using CT perfusion or MR diffusion. Unfortunately, these imaging modalities are not available in every hospital, and strict selection criteria might exclude patients who could still benefit from EVT. The presence of collaterals on CT angiography (CTA) may offer a more pragmatic imaging criterion that predicts possible benefit from EVT beyond 6 h from time last known well. The aim of this study is to assess the safety and efficacy of EVT for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow. Methods: The MR CLEAN-LATE trial is a multicenter, randomized, open-label, blinded endpoint trial, aiming to enroll 500 patients. We will investigate the efficacy of EVT between 6 and 24 h from time last known well in acute ischemic stroke due to a proximal intracranial anterior circulation occlusion confirmed by CTA or MRA. Patients with any collateral flow (poor, moderate, or good collaterals) on CTA will be included. The inclusion of poor collateral status will be restricted to a maximum of 100 patients. In line with the current Dutch guidelines, patients who fulfill the characteristics of included patients in DAWN and DEFUSE 3 will be excluded as they are eligible for EVT as standard care. The primary endpoint is functional outcome at 90 days, assessed with the modified Rankin Scale (mRS) score. Treatment effect will be estimated with ordinal logistic regression (shift analysis) on the mRS at 90 days. Secondary endpoints include clinical stroke severity at 24 h and 5–7 days assessed by the NIHSS, symptomatic intracranial hemorrhage, recanalization at 24 h, follow-up infarct size, and mortality at 90 days, Discussion: This study will provide insight into whether EVT is safe and effective for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow on CTA. Trial registration: NL58246.078.17, ISRCTN19922220, Registered on 11 December 2017
KW - Acute ischemic stroke
KW - Endovascular treatment
KW - Late arrivals
KW - Randomized controlled trial
KW - Thrombectomy
UR - http://www.scopus.com/inward/record.url?scp=85101776873&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/1745-6215-15-343
DO - https://doi.org/10.1186/1745-6215-15-343
M3 - Article
C2 - 25179366
SN - 1745-6215
VL - 22
SP - 343
JO - Trials
JF - Trials
IS - 1
M1 - 160
ER -