TY - JOUR
T1 - MR CLEAN-NO IV: intravenous treatment followed by endovascular treatment versus direct endovascular treatment for acute ischemic stroke caused by a proximal intracranial occlusion—study protocol for a randomized clinical trial
AU - Treurniet, Kilian M.
AU - LeCouffe, Natalie E.
AU - Kappelhof, Manon
AU - Emmer, Bart J.
AU - van Es, Adriaan C. G. M.
AU - Boiten, Jelis
AU - Lycklama, Geert J.
AU - Keizer, Koos
AU - Yo, Lonneke S. F.
AU - Lingsma, Hester F.
AU - van Zwam, Wim H.
AU - de Ridder, Inger
AU - van Oostenbrugge, Robert J.
AU - van der Lugt, Aad
AU - MR CLEAN-NO IV Investigators
AU - Dippel, Diederik W. J.
AU - Coutinho, Jonathan M.
AU - Roos, Yvo B. W. E. M.
AU - Majoie, Charles B. L. M.
N1 - 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. Amsterdam UMC, location AMC, and Erasmus MC received additional unrestricted funding on behalf of CONTRAST, for the execution of MR CLEAN-NO IV of Stryker. Funding Information: MR CLEAN-NO IV is executed within the CONTRAST consortium. The CONTRAST consortium is supported by Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, by the Brain Foundation Netherlands and powered by Health~Holland, Top Sector Life Sciences, and receives unrestricted funding from Medtronic and Cerenovus. CONTRAST is funded by a Cardiovascular Research the Netherlands (CVON) grant of the Dutch Heart Foundation, the Dutch brain foundation and industry partners. For MR CLEAN-NO IV, the consortium received an unrestricted grant from Stryker. The study is designed and will be conducted, analyzed, and interpreted by the investigators independently of the funders and sponsor. They will not have a role in writing the report and decision to submit for publication. Funding Information: DD and AvdL report that Erasmus MC received research grants from Dutch Heart Foundation, Dutch Brain Foundation, AngioCare BV, Covidien/EV3®, MEDAC Gmbh/LAMEPRO, Penumbra Inc., Stryker, and Top Medical/Concentric, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences & Health, Stryker, Thrombolytic Science, LLC, and Cerenovus. 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 treatment (EVT) has greatly improved the prognosis of acute ischemic stroke (AIS) patients with a proximal intracranial large vessel occlusion (LVO) of the anterior circulation. Currently, there is clinical equipoise concerning the added benefit of intravenous alteplase administration (IVT) prior to EVT. The aim of this study is to assess the efficacy and safety of omitting IVT before EVT in patients with AIS caused by an anterior circulation LVO. Methods: MR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients ≥ 18 years of age with a pre-stroke mRS < 3 with an LVO confirmed on CT angiography/MR angiography eligible for both IVT and EVT are randomized to receive either IVT (0.9 mg/kg) followed by EVT, or direct EVT in a 1:1 ratio. The primary objective is to assess superiority of direct EVT. Secondarily, non-inferiority of direct EVT compared to IVT before EVT will be explored. The primary outcome is the score on the modified Rankin Scale at 90 days. Ordinal regression with adjustment for prognostic variables will be used to estimate treatment effect. Secondary outcomes include reperfusion graded with the eTICI scale after EVT and stroke severity (National Institutes of Health Stroke Scale) at 24 h. Safety outcomes include intracranial hemorrhages scored according to the Heidelberg criteria. A total of 540 patients will be included. Discussion: IVT prior to EVT might facilitate early reperfusion before EVT or improved reperfusion rates during EVT. Conversely, among other potential adverse effects, the increased risk of bleeding could nullify the beneficial effects of IVT. MR CLEAN-NO IV will provide insight into whether IVT is still of added value in patients eligible for EVT. Trial registration: www.isrctn.com: ISRCTN80619088. Registered on 31 October 2017.
AB - Background: Endovascular treatment (EVT) has greatly improved the prognosis of acute ischemic stroke (AIS) patients with a proximal intracranial large vessel occlusion (LVO) of the anterior circulation. Currently, there is clinical equipoise concerning the added benefit of intravenous alteplase administration (IVT) prior to EVT. The aim of this study is to assess the efficacy and safety of omitting IVT before EVT in patients with AIS caused by an anterior circulation LVO. Methods: MR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients ≥ 18 years of age with a pre-stroke mRS < 3 with an LVO confirmed on CT angiography/MR angiography eligible for both IVT and EVT are randomized to receive either IVT (0.9 mg/kg) followed by EVT, or direct EVT in a 1:1 ratio. The primary objective is to assess superiority of direct EVT. Secondarily, non-inferiority of direct EVT compared to IVT before EVT will be explored. The primary outcome is the score on the modified Rankin Scale at 90 days. Ordinal regression with adjustment for prognostic variables will be used to estimate treatment effect. Secondary outcomes include reperfusion graded with the eTICI scale after EVT and stroke severity (National Institutes of Health Stroke Scale) at 24 h. Safety outcomes include intracranial hemorrhages scored according to the Heidelberg criteria. A total of 540 patients will be included. Discussion: IVT prior to EVT might facilitate early reperfusion before EVT or improved reperfusion rates during EVT. Conversely, among other potential adverse effects, the increased risk of bleeding could nullify the beneficial effects of IVT. MR CLEAN-NO IV will provide insight into whether IVT is still of added value in patients eligible for EVT. Trial registration: www.isrctn.com: ISRCTN80619088. Registered on 31 October 2017.
KW - Endovascular treatment
KW - Intravenous alteplase
KW - Ischemic stroke
UR - http://www.scopus.com/inward/record.url?scp=85101451876&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13063-021-05063-5
DO - https://doi.org/10.1186/s13063-021-05063-5
M3 - Article
C2 - 33588908
SN - 1745-6215
VL - 22
JO - Trials
JF - Trials
IS - 1
M1 - 141
ER -