CoChat
Sign Up
Cited by 229Acute Ischemic Stroke ManagementIntracranial Aneurysms: Treatment and ComplicationsCerebrovascular and Carotid Artery Diseases

Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial

Open access
Mitchell, Peter J, Yan, Bernard, Churilov, Leonid, Dowling, Richard J, Bush, Steven J, Bivard, Andrew, Huo, Xiao Chuan, Wang, Guoqing +68 more·2022·The Lancet
DOI 10.1016/s0140-6736(22)00564-5
Open this paper in CoChat — free account

Abstract

Background The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy).Methods DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0-2 or return to baseline at 90 days, with a non-inferiority margin of -0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants.Findings Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference -0·051, two-sided 95% CI -0·160 to 0·059; per-protocol risk difference -0·062, two-sided 95% CI -0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22-13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46-1·84).Interpretation We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment.Funding Australian National Health and Medical Research Council and Stryker USA.

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(22)00564-5

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Since many clinical differences between Western and non-Western populations have been reported, invariance in relevant features across these populations cannot be assumed but should be examined.

    “However, since many clinical differences between Western and non-Western populations have been reported, invariance in relevant features across these populations cannot be assumed but should be examined [3,40–42].”

    From Hasty generalizations and generics in medical research: A systematic review (2024) · cites this paper as [42]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Mitchell, P. J., Yan, B., Churilov, L., Dowling, R. J., Bush, S. J., Bivard, A., Huo, X. C., Wang, G., Zhang, S. Y., Ton, M. D., Cordato, D. J., Kleinig, T. J., Ma, H., Chandra, R. V., Brown, H., Campbell, B. C. V., Cheung, A. K., Steinfort, B., Scroop, R., Redmond, K., Miteff, F., Liu, Y., Duc, D. P., Rice, H., Parsons, M. W., Wu, T. Y., Nguyen, H.-T., Donnan, G. A., Miao, Z. R., Davis, S. M., Desmond, P., Yassi, N., Zhao, H., Williams, C., Alemseged, F., Ng, F. C., Yogendrakumar, V., Bailey, P., De Villiers, L., Phan, T., Thirugnanachandran, T., Chong, W., Asadi, H., Slater, L. A., Manning, N., Wenderoth, J., McDougall, A., Williams, C., Cappelen-Smith, C., Whitley, J., Edwards, L., Esperon, C. G., Spratt, N., Pepper, E., Levi, C., Faulder, K., Harrington, T., Krause, M., Waters, M., Fink, J., Ma, G., Shen, X., Song, X., Gao, Y., Guangxian, N., Guo, Z., Zhang, H., Han, H., Wang, H., Liao, G., Zhang, Z., Li, C., Yang, Z., Cai, C., Huang, C., & Hong, Y.
Affiliations
  • The Royal Melbourne Hospital (AU)
  • Binzhou People's Hospital (CN)
  • Hanoi Medical University (VN)
  • Liverpool Hospital (AU)
  • Royal Adelaide Hospital (AU)
  • Monash Medical Centre (AU)
  • Princess Alexandra Hospital (AU)
  • Royal North Shore Hospital (AU)
  • John Hunter Hospital (AU)
  • Yangzhou University (CN)
  • Gold Coast Hospital (AU)
  • Christchurch Hospital (NZ)
  • Capital Medical University (CN)
  • Pham Ngoc Thach University of Medicine (VN)
Corresponding author
  • Mitchell, Peter J
  • Bailey, Peter
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2022-07
Volume
400
Issue
10346
Pages
116-125
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(22)00564-5
OpenAlex
W4284897076
Cited by
229
References
27
Citations by year
2026: 32 · 2025: 44 · 2024: 56 · 2023: 80 · 2022: 17
FWCI
35.54
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Health Sciences › Medicine › Neurology › Intracranial Aneurysms: Treatment and Complications
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
Keywords
mechanical thrombectomy, acute ischemic stroke, large vessel occlusion, intravenous thrombolysis, alteplase, tenecteplase, bridging therapy, functional independence, modified Rankin Scale, non-inferiority, middle cerebral artery occlusion, basilar artery occlusion, internal carotid artery occlusion
MeSH terms
Adult, Australia, Brain Ischemia, Fibrinolytic Agents, Humans, Prospective Studies, Treatment Outcome, Thrombectomy, Stroke, Endovascular Procedures

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review