Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial
U. Fischer
(1, 2)
,
J. Kaesmacher
(1, 2)
,
D. Strbian
(3)
,
O. Eker
(4)
,
C. Cognard
(5)
,
P. S. Plattner
(1, 2)
,
L. Bütikofer
(1)
,
P. Mordasini
(1)
,
S. Deppeler
(1)
,
V. M. Pereira
(6)
,
J. F. Albucher
(7)
,
J. Darcourt
(8)
,
R. Bourcier
(9)
,
G. Benoit
(9)
,
C. Papagiannaki
(10)
,
O. Ozkul-Wermester
(11)
,
G. Sibolt
(12, 3)
,
M. Tiainen
(12, 3)
,
B. Gory
(13, 14)
,
S. Richard
(15, 16)
,
J. Liman
(17)
,
M. S. Ernst
(17)
,
M. Boulanger
(18)
,
C. Barbier
(18)
,
L. Mechtouff
(19)
,
L. Zhang
(20)
,
G. Marnat
(21)
,
I. Sibon
(22)
,
O. Nikoubashman
(23)
,
A. Reich
(23)
,
A. Consoli
(13, 24)
,
B. Lapergue
(24)
,
M. Ribó
(25)
,
A. Tomasello
(25)
,
S. Saleme
(26)
,
F. Macian
(26)
,
S. Moulin
(27)
,
P. Pagano
(27)
,
G. Saliou
(28)
,
E. Carrera
(29)
,
K. Janot
(30)
,
M. Hernández-Pérez
(31)
,
R. Pop
(32)
,
L. D. Schiava
(33)
,
A. R. Luft
(34)
,
M. Piotin
(35)
,
J. C. Gentric
(36, 37)
,
A. Pikula
(38, 6)
,
W. Pfeilschifter
(39)
,
Maurice Arnold
(2, 1)
,
A. H. Siddiqui
(40)
,
M. T. Froehler
(41)
,
A. J. Furlan
(42)
,
R. Chapot
(43)
,
M. Wiesmann
(23)
,
P. Machi
(44)
,
H. C. Diener
(45)
,
Z. Kulcsar
(34)
,
L. H. Bonati
(46, 47)
,
C. L. Bassetti
(2, 1)
,
M. Mazighi
(35, 48, 49, 50)
,
D. S. Liebeskind
(51)
,
J. L. Saver
(51)
,
J. Gralla
(2, 1)
1
UNIBE -
Universität Bern = University of Bern = Université de Berne
2 Inselspital - Bern University Hospital [Berne]
3 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
4 Service de neuroradiologie [Lyon]
5 Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse]
6 University of Toronto
7 Département Neurologie [CHU Toulouse]
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
10 Service de Radiologie [CHU Rouen]
11 Service de neurologie [Rouen]
12 HUS - Helsinki University Hospital [Finland]
13 IADI - Imagerie Adaptative Diagnostique et Interventionnelle
14 Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy]
15 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
16 Service de neurologie [CHRU Nancy]
17 UMG - University Medical Center Göttingen
18 CHU Caen
19 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
20 St George’s University Hospitals
21 DNR - Bordeaux - Département de Neuro-Radiologie [Bordeaux]
22 INCIA - Institut de Neurosciences cognitives et intégratives d'Aquitaine
23 UKA - Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany]
24 Hôpital Foch [Suresnes]
25 Vall d'Hebron University Hospital [Barcelona]
26 CHU Limoges
27 CHU Reims - Hôpital universitaire Robert Debré [Reims]
28 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
29 HUG - Hôpitaux Universitaires de Genève
30 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
31 GTPUH - Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain]
32 Département de Neuroradiologie [Strasbourg]
33 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
34 University hospital of Zurich [Zurich]
35 Fondation Ophtalmologique Adolphe de Rothschild [Paris]
36 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
37 Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
38 Toronto Western Hospital
39 Frankfurt University Hospital
40 SUNY Buffalo - University at Buffalo [SUNY]
41 Vanderbilt University Medical Center [Nashville]
42 Case Western Reserve University [Cleveland]
43 Alfried Krupp Krankenhaus [Essen]
44 Geneva University Hospitals and Geneva University
45 IMIBE - Institute of Medical Informatics, Biometrics and Epidemiology [ Essen, Germany]
46 University Hospital Basel [Basel]
47 Unibas - Université de Bâle = University of Basel = Basel Universität
48 LVTS (UMR_S_1148 / U1148) - Laboratoire de Recherche Vasculaire Translationnelle
49 Hôpital Lariboisière-Fernand-Widal [APHP]
50 GHU-PPN - FHU NeuroVasc [Site Sainte-Anne, Paris]
51 David Geffen School of Medicine [Los Angeles]
2 Inselspital - Bern University Hospital [Berne]
3 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
4 Service de neuroradiologie [Lyon]
5 Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse]
6 University of Toronto
7 Département Neurologie [CHU Toulouse]
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
10 Service de Radiologie [CHU Rouen]
11 Service de neurologie [Rouen]
12 HUS - Helsinki University Hospital [Finland]
13 IADI - Imagerie Adaptative Diagnostique et Interventionnelle
14 Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy]
15 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
16 Service de neurologie [CHRU Nancy]
17 UMG - University Medical Center Göttingen
18 CHU Caen
19 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
20 St George’s University Hospitals
21 DNR - Bordeaux - Département de Neuro-Radiologie [Bordeaux]
22 INCIA - Institut de Neurosciences cognitives et intégratives d'Aquitaine
23 UKA - Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany]
24 Hôpital Foch [Suresnes]
25 Vall d'Hebron University Hospital [Barcelona]
26 CHU Limoges
27 CHU Reims - Hôpital universitaire Robert Debré [Reims]
28 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
29 HUG - Hôpitaux Universitaires de Genève
30 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
31 GTPUH - Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain]
32 Département de Neuroradiologie [Strasbourg]
33 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
34 University hospital of Zurich [Zurich]
35 Fondation Ophtalmologique Adolphe de Rothschild [Paris]
36 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
37 Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
38 Toronto Western Hospital
39 Frankfurt University Hospital
40 SUNY Buffalo - University at Buffalo [SUNY]
41 Vanderbilt University Medical Center [Nashville]
42 Case Western Reserve University [Cleveland]
43 Alfried Krupp Krankenhaus [Essen]
44 Geneva University Hospitals and Geneva University
45 IMIBE - Institute of Medical Informatics, Biometrics and Epidemiology [ Essen, Germany]
46 University Hospital Basel [Basel]
47 Unibas - Université de Bâle = University of Basel = Basel Universität
48 LVTS (UMR_S_1148 / U1148) - Laboratoire de Recherche Vasculaire Translationnelle
49 Hôpital Lariboisière-Fernand-Widal [APHP]
50 GHU-PPN - FHU NeuroVasc [Site Sainte-Anne, Paris]
51 David Geffen School of Medicine [Los Angeles]
U. Fischer
- Fonction : Auteur correspondant
O. Eker
- Fonction : Auteur
- PersonId : 174182
- IdHAL : omer-eker
- ORCID : 0000-0002-5696-5368
- IdRef : 139448691
L. Mechtouff
- Fonction : Auteur
- PersonId : 1171166
- ORCID : 0000-0001-9165-5763
- IdRef : 121718751
Maurice Arnold
- Fonction : Auteur
- PersonId : 938257
Résumé
Background: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke.
Methods: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants.
Findings: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047).
Interpretation: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients.
Domaines
Neurosciences
Fichier sous embargo
Fichier sous embargo
Date de visibilité indéterminée