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Original research
Systemic THrombolysis Randomization IN Endovascular Stroke Therapy (SHRINE) Collaboration: a patient-level pooled analysis of the SKIP and DEVT Trials
  1. Raul G Nogueira1,
  2. Kazumi Kimura2,
  3. Yuji Matsumaru3,
  4. Kentaro Suzuki2,
  5. Zhongming Qiu4,5,
  6. Wenjie Zi4,6,
  7. Timothy P Moran7,
  8. Fengli Li4,
  9. Hongfei Sang4,
  10. Weidong Luo4,
  11. Shuai Liu4,
  12. Junjie Yuan4,
  13. Jiaxing Song4,
  14. Jiacheng Huang4,
  15. Masataka Takeuchi8,
  16. Masafumi Morimoto9,
  17. Toshiaki Otsuka10,
  18. Qingwu Yang4
  1. 1 Department of Neurology and Neurosurgery, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
  2. 2 Department of Neurology, Nippon Medical School, Tokyo, Japan
  3. 3 Division of Stroke Prevention and Treatment, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
  4. 4 Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China
  5. 5 Department of Neurology, 903th Hospital of PLA, Hangzhou, Zhejiang, China
  6. 6 Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
  7. 7 Department of Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
  8. 8 Department of Neurosurgery, Seisho Hospital, Kanagawa, Japan
  9. 9 Department of Neurosurgery, Yokohama Shintoshi Neurosurgery Hospital, Kanagawa, Yokohama, Japan
  10. 10 Department of Hygiene and Public Health, Nippon Medical School, Bunkyo-ku, Japan
  1. Correspondence to Dr Raul G Nogueira, Department of Neurology and Neurosurgery, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA; raul.g.nogueira{at}


Objective To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups.

Methods We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0–2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality.

Results We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable.

Conclusions The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.

  • Stroke
  • Thrombolysis
  • Thrombectomy

Data availability statement

Data are available upon reasonable request. Data pertaining to this study are available upon reasonable request to the corresponding author.

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Data availability statement

Data are available upon reasonable request. Data pertaining to this study are available upon reasonable request to the corresponding author.

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  • Contributors All authors contributed to the acquisition of the data. RGN and TPM contributed to the analysis of data. RGN wrote the first manuscript draft. TPM prepared the figures. All authors have reviewed and approved the contents of this manuscript. This study results from two multicenter randomized trials requiring the collaboration of multiple investigators. All authors meet the ICJME criteria for authorship.

    RGN accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

  • Funding Funding for the SKIP trial was provided by the Japanese Society for Neuroendovascular Therapy. The DEVT trial was supported by grants 81525008, 81901236, 81801157 from the National Natural Science Foundation of China, 2019ZX001 from the Chongqing Major Disease Prevention and Control Technology Research Project, 2019XLC2008 2019XLC3016 from the Clinical Medical Research Talent Training Program of Army Medical University, and 2018JSLC0017 from the Major Clinical Innovation Technology Project of the Second Affiliated Hospital of Army Medical University.

  • Competing interests RGN reports consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron; stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze. RGN is one of the principal investigators of the ‘Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW)’ trial. Funding for this project is provided by Cerenovus. RGN is the principal investigator of the ‘Combined Thrombectomy for Distal MediUm Vessel Occlusion StroKe (DUSK)’ trial. Funding for this project is provided by Stryker Neurovascular. RGN is an investor in Viz-AI, Perfuze, Cerebrotech, Reist/Q’Apel Medical, Truvic, Vastrax, and Viseon.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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