Kilian M Treurniet1, Natalie E LeCouffe1,2, Manon Kappelhof1, Yvo B W E M Roos2, Charles B L M Majoie3, Bart J Emmer1, Adriaan C G M van Es4, Jelis Boiten5, Geert J Lycklama6, Koos Keizer7, Lonneke S F Yo8, Hester F Lingsma9, Wim H van Zwam10, Inger de Ridder11, Robert J van Oostenbrugge11, Aad van der Lugt12, Diederik W J Dippel13, Jonathan M Coutinho2. 1. Department of Radiology & Nuclear Medicine, Amsterdam UMC, University of Amsterdam, P.O. Box 22660, Amsterdam, 1100DD, The Netherlands. 2. Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 3. Department of Radiology & Nuclear Medicine, Amsterdam UMC, University of Amsterdam, P.O. Box 22660, Amsterdam, 1100DD, The Netherlands. c.b.majoie@amsterdamumc.nl. 4. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. 5. Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands. 6. Department of Radiology, The Hague Medical Center, The Hague, The Netherlands. 7. Department of Neurology, Catharina Hospital, Eindhoven, The Netherlands. 8. Department of Radiology, Catharina Hospital, Eindhoven, The Netherlands. 9. Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands. 10. Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands. 11. Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands. 12. Department of Radiology & Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. 13. Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Abstract
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.
RCT Entities:
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.
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