A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke

被引：321

作者：

LeCouffe, N. E. ^{[1
]}

Kappelhof, M. ^{[2
]}

Treurniet, K. M. ^{[2
,4
]}

Rinkel, L. A. ^{[1
]}

Bruggeman, A. E. ^{[2
]}

Berkhemer, O. A. ^{[2
,3
,8
]}

Wolff, L. ^{[8
]}

van Voorst, H. ^{[2
,3
]}

Tolhuisen, M. L. ^{[2
,3
]}

Dippel, D. W. J. ^{[9
]}

van der Lugt, A. ^{[8
]}

van Es, A. C. G. M. ^{[11
]}

Boiten, J. ^{[5
]}

Nijeholt, G. J. Lycklama A. ^{[4
]}

Keizer, K. ^{[12
]}

Gons, R. A. R. ^{[12
]}

Yo, L. S. F. ^{[13
]}

van Oostenbrugge, R. J. ^{[14
]}

van Zwam, W. H. ^{[15
]}

Roozenbeek, B. ^{[9
]}

van der Worp, H. B. ^{[17
]}

Lo, R. T. H. ^{[18
]}

van den Wijngaard, I. R. ^{[4
,5
]}

de Ridder, I. R. ^{[14
]}

Costalat, V. ^{[37
]}

Arquizan, C. ^{[38
]}

Lemmens, R. ^{[41
,42
,43
]}

Demeestere, J. ^{[41
,42
,43
]}

Hofmeijer, J. ^{[19
]}

Martens, J. M. ^{[20
]}

Schonewille, W. J. ^{[21
]}

Vos, J. -A. ^{[22
]}

Uyttenboogaart, M. ^{[23
]}

Bokkers, R. P. H. ^{[24
]}

van Tuijl, J. H. ^{[25
]}

Kortman, H. ^{[26
]}

Schreuder, F. H. B. M. ^{[27
]}

Boogaarts, H. D. ^{[28
]}

de Laat, K. F. ^{[6
]}

van Dijk, L. C. ^{[7
]}

den Hertog, H. M. ^{[29
]}

van Hasselt, B. A. A. M. ^{[30
]}

Brouwers, P. J. A. M. ^{[31
]}

Bulut, T. ^{[32
]}

Remmers, M. J. M. ^{[33
]}

van Norden, A. ^{[33
]}

Imani, F. ^{[34
]}

Rozeman, A. D. ^{[35
]}

Elgersma, O. E. H. ^{[36
]}

Desfontaines, P. ^{[44
]}

机构：

[1] Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Neurol, Amsterdam, Netherlands

[2] Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Radiol & Nucle Med, Amsterdam, Netherlands

[3] Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Biomed Engn & Phys, Amsterdam, Netherlands

[4] Hague Med Ctr, Dept Radiol, The Hague, Netherlands

[5] Hague Med Ctr, Dept Neurol, The Hague, Netherlands

[6] Haga Hosp, Dept Neurol, The Hague, Netherlands

[7] Haga Hosp, Dept Radiol, The Hague, Netherlands

[8] Erasmus MC, Univ Med Ctr, Dept Radiol & Nucl Med, Rotterdam, Netherlands

[9] Erasmus MC, Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands

[10] Erasmus MC, Univ Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands

[11] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands

[12] Catharina Hosp, Dept Neurol, Eindhoven, Netherlands

[13] Catharina Hosp, Dept Radiol, Eindhoven, Netherlands

[14] Cardiovasc Res Inst Maastricht, Dept Neurol, Maastricht, Netherlands

[15] Maastricht Univ, Med Ctr, Dept Radiol & Nucl Med, Maastricht, Netherlands

[16] Maastricht Univ, Sch Mental Hlth & Sci, Maastricht, Netherlands

[17] Univ Med Ctr Utrecht, Brain Ctr, Dept Neurol & Neurosurg, Utrecht, Netherlands

[18] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands

[19] Rijnstate Hosp, Dept Neurol, Arnhem, Netherlands

[20] Rijnstate Hosp, Dept Radiol, Arnhem, Netherlands

[21] St Antonius Hosp, Dept Neurol, Nieuwegein, Netherlands

[22] St Antonius Hosp, Dept Radiol, Nieuwegein, Netherlands

[23] Univ Med Ctr Groningen, Dept Neurol, Groningen, Netherlands

[24] Univ Med Ctr Groningen, Radiol Med Imaging Ctr, Groningen, Netherlands

[25] Elisabeth TweeSteden Hosp, Dept Neurol, Tilburg, Netherlands

[26] Elisabeth TweeSteden Hosp, Dept Radiol, Tilburg, Netherlands

[27] Radboud Univ Nijmegen Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands

[28] Radboud Univ Nijmegen Med Ctr, Dept Neurosurg, Nijmegen, Netherlands

[29] Isala Hosp, Dept Neurol, Zwolle, Netherlands

[30] Isala Hosp, Dept Radiol & Nucl Med, Zwolle, Netherlands

[31] Medisch Spectrum Twente, Dept Neurol, Enschede, Netherlands

[32] Medisch Spectrum Twente, Dept Radiol, Enschede, Netherlands

[33] Amphia Hosp, Dept Neurol, Breda, Netherlands

[34] Amphia Hosp, Dept Radiol, Breda, Netherlands

[35] Albert Schweitzer Hosp, Dept Neurol, Dordrecht, Netherlands

[36] Albert Schweitzer Hosp, Dept Radiol, Dordrecht, Netherlands

[37] Ctr Hosp Univ Montpellier, Dept Neuroradiol, Montpellier, France

[38] Ctr Hosp Univ Montpellier, Dept Neurol, Montpellier, France

[39] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, Dept Neurol, Paris, France

[40] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, Dept Neuroradiol, Paris, France

[41] Univ Leuven, KU Leuven, Dept Neurosci, Expt Neurol, Leuven, Belgium

[42] Univ Hosp Leuven, Dept Neurol, Vlaams Inst Biotechnol, Ctr Brain & Dis Res, Leuven, Belgium

[43] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium

[44] Ctr Hosp Chretien, Dept Neurol, Liege, Belgium

[45] Ctr Hosp Chretien, Dept Radiol, Liege, Belgium

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2021年 / 385卷 / 20期

关键词：

ACUTE ISCHEMIC-STROKE; MECHANICAL THROMBECTOMY; THROMBOLYSIS; GUIDELINES; THERAPY; CARE;

D O I：

10.1056/NEJMoa2107727

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 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, .)

引用

页码：1833 / 1844

页数：12

共 27 条

[1] INTEROBSERVER AGREEMENT FOR THE ASSESSMENT OF HANDICAP IN STROKE PATIENTS [J].

BAMFORD, JM ;

SANDERCOCK, PAG ;

WARLOW, CP ;

SLATTERY, J .

STROKE, 1989, 20 (06) :828-828

[2] A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke [J].

Berkhemer, O. A. ;

Fransen, P. S. S. ;

Beumer, D. ;

van den Berg, L. A. ;

Lingsma, H. F. ;

Yoo, A. J. ;

Schonewille, W. J. ;

Vos, J. A. ;

Nederkoorn, P. J. ;

Wermer, M. J. H. ;

van Walderveen, M. A. A. ;

Staals, J. ;

Hofmeijer, J. ;

van Oostayen, J. A. ;

Nijeholt, G. J. Lycklama A. ;

Boiten, J. ;

Brouwer, P. A. ;

Emmer, B. J. ;

de Bruijn, S. F. ;

van Dijk, L. C. ;

Kappelle, L. J. ;

Lo, R. H. ;

Van Dijk, E. J. ;

de Vries, J. ;

de Kort, P. L. M. ;

van Rooij, W. J. J. ;

van den Berg, J. S. P. ;

van Hasselt, B. A. A. M. ;

Aerden, L. A. M. ;

Dallinga, R. J. ;

Visser, M. C. ;

Bot, J. C. J. ;

Vroomen, P. C. ;

Eshghi, O. ;

Schreuder, T. H. C. M. L. ;

Heijboer, R. J. J. ;

Keizer, K. ;

Tielbeek, A. V. ;

den Hertog, H. M. ;

Gerrits, D. G. ;

van den Berg-Vos, R. M. ;

Karas, G. B. ;

Steyerberg, E. W. ;

Flach, H. Z. ;

Marquering, H. A. ;

Sprengers, M. E. S. ;

Jenniskens, S. F. M. ;

Beenen, L. F. M. ;

van den Berg, R. ;

Koudstaal, P. J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (01) :11-20

[3] Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke [J].

Goyal, M. ;

Demchuk, A. M. ;

Menon, B. K. ;

Eesa, M. ;

Rempel, J. L. ;

Thornton, J. ;

Roy, D. ;

Jovin, T. G. ;

Willinsky, R. A. ;

Sapkota, B. L. ;

Dowlatshahi, D. ;

Frei, D. F. ;

Kamal, N. R. ;

Montanera, W. J. ;

Poppe, A. Y. ;

Ryckborst, K. J. ;

Silver, F. L. ;

Shuaib, A. ;

Tampieri, D. ;

Williams, D. ;

Bang, O. Y. ;

Baxter, B. W. ;

Burns, P. A. ;

Choe, H. ;

Heo, J. -H. ;

Holmstedt, C. A. ;

Jankowitz, B. ;

Kelly, M. ;

Linares, G. ;

Mandzia, J. L. ;

Shankar, J. ;

Sohn, S. -I. ;

Swartz, R. H. ;

Barber, P. A. ;

Coutts, S. B. ;

Smith, E. E. ;

Morrish, W. F. ;

Weill, A. ;

Subramaniam, S. ;

Mitha, A. P. ;

Wong, J. H. ;

Lowerison, M. W. ;

Sajobi, T. T. ;

Hill, M. D. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (11) :1019-1030

[4] Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials [J].

Goyal, Mayank ;

Menon, Bijoy K. ;

van Zwam, Wim H. ;

Dippel, Diederik W. J. ;

Mitchell, Peter J. ;

Demchuk, Andrew M. ;

Davalos, Antoni ;

Majoie, Charles B. L. M. ;

van der Lugt, Aad ;

de Miquel, Maria A. ;

Donnan, Geoff Rey A. ;

Roos, Yvo B. W. E. M. ;

Bonafe, Alain ;

Jahan, Reza ;

Diener, Hans-Christoph ;

van den Berg, Lucie A. ;

Levy, Elad I. ;

Berkhemer, Olvert A. ;

Pereira, Vitor M. ;

Rempel, Jeremy ;

Millan, Monica ;

Davis, Stephen M. ;

Roy, Daniel ;

Thornton, John ;

San Roman, Luis ;

Ribo, Marc ;

Beumer, Debbie ;

Stouch, Bruce ;

Brown, Scott ;

Campbell, Bruce C. V. ;

van Oostenbrugge, Robert J. ;

Saver, Jeff Rey L. ;

Hill, Michael D. ;

Jovin, Tudor G. .

LANCET, 2016, 387 (10029) :1723-1731

[5]

Harrell F.E., 2001, Regression Modeling Strategies

[6] Comparison of Telephone and Face-to-Face Assessment of the Modified Rankin Scale [J].

Janssen, Paula M. ;

Visser, Nora A. ;

Mees, Sanne M. Dorhout ;

Klijn, Catharina J. M. ;

Algra, Ale ;

Rinkel, Gabriel J. E. .

CEREBROVASCULAR DISEASES, 2010, 29 (02) :137-139

[7] Bridging Therapy with i. v. rtPA in MCA Occlusion Prior to Endovascular Thrombectomy: a Double-Edged Sword? [J].

Kaesmacher, Johannes ;

Kleine, Justus F. .

CLINICAL NEURORADIOLOGY, 2018, 28 (01) :81-89

[8]

Katsanos A., 2021, NEUROLOGY

[9] Informed consent procedures for emergency interventional research in patients with traumatic brain injury and ischaemic stroke [J].

Kompanje, Erwin J. O. ;

van Dijck, Jeroen T. J. M. ;

Chalos, Vicky ;

van den Berg, Sophie A. ;

Janssen, Paula M. ;

Nederkoorn, Paul J. ;

van der Jagt, Mathieu ;

Citerio, Giuseppe ;

Stocchetti, Nino ;

Dippel, Diederik W. J. ;

Peul, Wilco C. .

LANCET NEUROLOGY, 2020, 19 (12) :1033-1042

[10] Noninferiority Margins in Trials of Thrombectomy Devices for Acute Ischemic Stroke: Is the Bar Being Set Too Low? [J].

Lin, Chun-Jen ;

Saver, Jeffrey L. .

STROKE, 2019, 50 (12) :3519-3526

← 1 2 3 →