TY - JOUR
T1 - A randomized trial of intravenous alteplase before endovascular treatment for stroke
AU - LeCouffe, Natalie E.
AU - Kappelhof, Manon
AU - Treurniet, Kilian M.
AU - Rinkel, Leon A.
AU - Bruggeman, Agnetha E.
AU - Berkhemer, Olvert A.
AU - Wolff, Lennard
AU - van Voorst, Henk
AU - Tolhuisen, Manon L.
AU - Dippel, Diederik W. J.
AU - van der Lugt, Aad
AU - van Es, Adriaan C. G. M.
AU - Boiten, Jelis
AU - Lycklama à Nijeholt, Geert J.
AU - Keizer, Koos
AU - Gons, Rob A. R.
AU - Yo, Lonneke S. F.
AU - van Oostenbrugge, Robert J.
AU - van Zwam, Wim H.
AU - Roozenbeek, Bob
AU - van der Worp, H. Bart
AU - Lo, Rob T. H.
AU - van den Wijngaard, Ido R.
AU - de Ridder, Inger R.
AU - Costalat, Vincent
AU - Arquizan, Caroline
AU - Lemmens, Robin
AU - Demeestere, Jelle
AU - Hofmeijer, Jeannette
AU - Martens, Jasper M.
AU - Schonewille, Wouter J.
AU - Vos, Jan-Albert
AU - Uyttenboogaart, Maarten
AU - Bokkers, Reinoud P. H.
AU - van Tuijl, Julia H.
AU - Kortman, Hans
AU - Schreuder, Floris H. B. M.
AU - Boogaarts, Hieronymus D.
AU - de Laat, Karlijn F.
AU - van Dijk, Lukas C.
AU - den Hertog, Heleen M.
AU - van Hasselt, Boudewijn A. A. M.
AU - Brouwers, Paul J. A. M.
AU - Bulut, Tomas
AU - MR CLEAN-NO IV Investigators
AU - van den Berg, René
AU - Beenen, Ludo F. M.
AU - Emmer, Bart J.
AU - Coutinho, Jonathan M.
AU - Majoie, Charles B. L. M.
AU - Roos, Yvo B. W. E. M.
N1 - Funding Information: The trial was funded by the Collaboration for New Treatments of Acute Stroke consortium, which is funded by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Cerenovus, and Stryker. There was no commercial involvement in the design or planning of the trial or in the analysis or reporting of the data by any of the parties providing funding. The trial used a deferred-consent procedure in accordance with national legislation in the participating countries.16 Patients or their legal representatives were asked to provide written informed consent as soon as possible after treatment. Patient eligibility was assessed by the treating physician. Members of the executive and steering committees designed the trial and protocol, collected the data, met monthly to oversee the trial, and wrote the manuscript. The authors vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol. Funding Information: Supported by the Collaboration for New Treatments of Acute Stroke (CONTRAST) consortium, which is supported by the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation (CVON2015-01: CONTRAST); the Brain Foundation Netherlands (HA2015.01.06); the Ministry of Economic Affairs by means of the PPP Allowance made available by Top Sector Life Sciences and Health to stimulate public–private partnerships (LSHM17016); and unrestricted funding by Stryker, Medtronic, and Cerenovus. Publisher Copyright: Copyright © 2021 Massachusetts Medical Society.
PY - 2021/11/11
Y1 - 2021/11/11
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Combined Modality Therapy
KW - Endovascular Procedures
KW - Europe
KW - Female
KW - Fibrinolytic Agents/therapeutic use
KW - Humans
KW - Infusions, Intravenous
KW - Ischemic Stroke/drug therapy
KW - Male
KW - Middle Aged
KW - Severity of Illness Index
KW - Thrombectomy
KW - Tissue Plasminogen Activator/therapeutic use
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=85120074229&partnerID=8YFLogxK
U2 - https://doi.org/10.1056/NEJMoa2107727
DO - https://doi.org/10.1056/NEJMoa2107727
M3 - Article
C2 - 34758251
SN - 0028-4793
VL - 385
SP - 1833
EP - 1844
JO - New England journal of medicine
JF - New England journal of medicine
IS - 20
ER -