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

Treurniet, K.M.; LeCouffe, N.E.; Kappelhof, M.; Emmer, B.J.; Es, A.C.G.M. van; Boiten, J.; Lycklama, G.J.; Keizer, K.; Yo, L.S.F.; Lingsma, H.F.; Zwam, W.H. van; Ridder, I. de; Oostenbrugge, R.J. van; Lugt, A. van der; Dippel, D.W.J.; Coutinho, J.M.; Roos, Y.B.W.E.M.; Majoie, C.B.L.M.; MR CLEAN-NO IV Investigators

doi:doi:10.1186/s13063-021-05063-5

BackgroundEndovascular 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.MethodsMR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients >= 18years 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 (0.9mg/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...Show moreBackgroundEndovascular 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.MethodsMR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients >= 18years 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 (0.9mg/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 90days. 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 24h. Safety outcomes include intracranial hemorrhages scored according to the Heidelberg criteria. A total of 540 patients will be included.DiscussionIVT 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 registrationwww.isrctn.com: ISRCTN80619088. Registered on 31 October 2017.Show less

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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