Background Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment... Show moreBackground Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA).Methods MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220. Findings Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1 center dot 67 [95% CI 1 center dot 20-2 center dot 32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0 center dot 72 [95% CI 0 center dot 44-1 center dot 18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4 center dot 59 [95% CI 1 center dot 49-14 center dot 10]). Interpretation In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow.Funding Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.Copyright (c) 2023 Elsevier Ltd. All rights reserved. Show less
Compagne, K.C.J.; Kappelhof, M.; Hinsenveld, W.H.; Brouwer, J.; Goldhoorn, R.J.B.; Uyttenboogaart, M.; ... ; MR CLEAN Registry Investigators 2022
Background: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to... Show moreBackground: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes. Methods: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days). Results: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; PP<0.001, respectively). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 66%; P<0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07-1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98-1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99-1.30]). Outcomes were consistent in the analysis per chronological quartile. Conclusions: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates. Show less
LeCouffe, N.E.; Kappelhof, M.; Treurniet, K.M.; Rinkel, L.A.; Bruggeman, A.E.; Berkhemer, O.A.; ... ; MR CLEAN-NO IV Investigators 2021
Alteplase with EVT versus EVT Alone for Stroke Trials involving Asian patients with acute stroke have suggested that endovascular treatment alone is not inferior to the usual practice of... Show moreAlteplase with EVT versus EVT Alone for Stroke Trials involving Asian patients with acute stroke have suggested that endovascular treatment alone is not inferior to the usual practice of thrombolysis before endovascular treatment. This trial involving European patients did not show noninferiority or superiority of endovascular treatment alone.Background The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. Methods We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. Results The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P=0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). Conclusions In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, .) Show less
Background The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied.Methods We randomly assigned patients within 6 hours after... Show moreBackground The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied.Methods We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days.Results A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12).Conclusions Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.)Endovascular Therapy for Basilar-Artery Stroke In a randomized trial involving 300 patients with basilar-artery stroke, endovascular thrombectomy was not significantly different from medical therapy with respect to a favorable functional outcome (modified Rankin scale score of 0 to 3) at 90 days, but a clinically significant benefit could not be excluded. Show less
Schaafsma, J.D.; Velthuis, B.K.; Berg, R. van den; Brouwer, P.A.; Majoie, C.B.L.M.; Barkhof, F.; ... ; Rinkel, G.J.E. 2012
Purpose: To determine the test characteristics of magnetic resonance (MR) angiography in the assessment of occlusion of aneurysms treated with coil placement. Materials and Methods: This was an... Show morePurpose: To determine the test characteristics of magnetic resonance (MR) angiography in the assessment of occlusion of aneurysms treated with coil placement. Materials and Methods: This was an ethics committee-approved multicenter study. Written informed consent was obtained in 311 patients with 343 aneurysms, who had been treated with coil placement and were scheduled for routine follow-up with intraarterial digital subtraction angiography (DSA). Thirty-five patients participated two or three times. Either 3.0- or 1.5-T time-of-flight (TOF) and contrast material-enhanced MR angiography were performed in addition to intraarterial DSA. Aneurysm occlusion was evaluated by independent readers at DSA and MR angiography. The test characteristics of MR angiography were assessed by using DSA as the standard. The area under the receiver operating characteristic curve (AUC) was calculated for 3.0- versus 1.5-T MR angiography and for TOF versus contrast-enhanced MR angiography, and factors associated with discrepancies between MR angiography and DSA were assessed with logistic regression. Results: Aneurysm assessments (n = 381) at DSA and MR angiography were compared. Incomplete occlusion was seen at DSA in 88 aneurysms (23%). Negative predictive value of MR angiography was 94% (95% confidence interval [ CI]: 91%, 97%), positive predictive value was 69% (95% CI: 60%, 78%), sensitivity was 82% (95% CI: 72%, 89%), and specificity was 89% (95% CI: 85%, 93%). AUCs were similar for 3.0- (0.90 [ 95% CI: 0.86, 0.94]) and 1.5-T MR (0.87 [ 95% CI: 0.78, 0.95]) and for TOF MR (0.86 [ 95% CI: 0.81, 0.91]) versus contrast-enhanced MR (0.85 [ 95% CI: 0.80, 0.91]). A small residual lumen (odds ratio, 2.1 [ 95% CI: 1.1, 4.3]) and suboptimal projection at DSA (odds ratio, 5.5 [ 95% CI: 1.5, 21.0]) were independently associated with discordance between intraarterial DSA and MR angiography. Conclusion: Documentation of good diagnostic performance of TOF MR angiography at both 1.5 and 3.0 T in the current study represents an important step toward replacing intraarterial DSA with MR angiography in the follow-up of patients with aneurysms treated with coils. (C) RSNA, 2010 Show less
