Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021 Jan 19;325(3):244-253.
doi: 10.1001/jama.2020.23522.

Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial

Kentaro Suzuki  1 , Yuji Matsumaru  2 , Masataka Takeuchi  3 , Masafumi Morimoto  4 , Ryuzaburo Kanazawa  5 , Yohei Takayama  6 , Yuki Kamiya  7 , Keigo Shigeta  8 , Seiji Okubo  9 , Mikito Hayakawa  2 , Norihiro Ishii  10 , Yorio Koguchi  11 , Tomoji Takigawa  12 , Masato Inoue  13 , Hiromichi Naito  14 , Takahiro Ota  15 , Teruyuki Hirano  16 , Noriyuki Kato  17 , Toshihiro Ueda  18 , Yasuyuki Iguchi  19 , Kazunori Akaji  20 , Wataro Tsuruta  21 , Kazunori Miki  22 , Shigeru Fujimoto  23 , Tetsuhiro Higashida  5 , Mitsuhiro Iwasaki  4 , Junya Aoki  1 , Yasuhiro Nishiyama  1 , Toshiaki Otsuka  24 , Kazumi Kimura  1 ; SKIP Study Investigators
Affiliations
Randomized Controlled Trial

Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial

Kentaro Suzuki et al. JAMA. .

Erratum in

Abstract

Importance: Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear.

Objective: To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome.

Design, setting, and participants: Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019.

Interventions: Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103).

Main outcomes and measures: The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours.

Results: Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, -11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, -0.8% [95% CI, -9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, -16.8% [95% CI, -32.1% to -1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, -1.8% [95% CI, -9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78).

Conclusions and relevance: Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority.

Trial registration: umin.ac.jp/ctr Identifier: UMIN000021488.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Suzuki reported receiving grants from the Japanese Society for Neuroendovascular Therapy during the conduct of the study and a scholarship to study abroad from the Uehara Memorial Foundation. Dr Matsumaru reported receiving personal fees from Medtronic Co Ltd, Stryker Co Ltd, Sanofi Co Ltd, Daiichi Sankyo Co Ltd, Otsuka Pharmaceutical Co Ltd, and Biomedical Solutions outside the submitted work. Dr Takeuchi reported receiving lecture fees from Stryker Co Ltd outside the submitted work. Dr Kamiya reported receiving personal fees from Daiichi Sankyo Co Ltd and grants from Bristol-Myers Squibb Co Ltd outside the submitted work. Dr Hirano reported receiving personal fees from Bayer Healthcare Co Ltd, Daiichi Sankyo Co Ltd, Nippon Boehringer Ingelheim Co Ltd, Bristol-Myers Squibb Co Ltd, Medtronic Co Ltd, Sanofi Co Ltd, Otsuka Pharmaceutical Co Ltd, Mitsubishi Tanabe Pharma Co, CSL Behring KK, Astellas Pharma Inc, and Pfizer Japan Inc outside the submitted work. Dr Iguchi reported receiving grants and personal fees from Sanofi SA, Daiichi-Sankyo Co Ltd, and Boehringer Ingelheim GmbH, Bayer AG; personal fees from Pfizer Inc and Bristol-Myers Squibb; and lecture fees from Bayer Healthcare Co Ltd, Pfizer Japan Inc, Nippon Boehringer Ingelheim Co Ltd, Takeda Pharmaceutical Co Ltd, Otsuka Pharmaceutical Co Ltd, and Daiichi Sankyo Co Ltd outside the submitted work. Dr Fujimoto reported receiving personal fees from Daiichi Sankyo Co Ltd, Bayer Yakuhin Ltd, Nippon Boehringer Ingelheim Co Ltd, Bristol-Myers Squibb Co, Pfizer Japan Inc, Takeda Pharmaceutical Co Ltd, Otsuka Pharmaceutical Co Ltd, Sanofi KK, MSD KK, and Dai-Nippon Sumitomo Pharma Co Ltd outside the submitted work. Dr Nishiyama reported receiving personal fees from Daiichi Sankyo Co Ltd outside the submitted work. Dr Kimura reported receiving grants from 38th Mihara Cerebrovascular Disorder Research Promotion Fund Ltd during the conduct of the study and grants from Teijin Pharma Ltd, Medtronic Co Ltd, Pfizer Japan Inc, Daiichi Sankyo Co, and Nippon Boehringer Ingelheim Co Ltd, personal fees from Daiichi Sankyo Co, personal fees from Bayer Healthcare Co Ltd and personal fees from Nippon Boehringer Ingelheim Co Ltd and Bristol-Myers Squibb Co Ltd outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Enrollment, Randomization, and Treatment of the SKIP Randomized Clinical Trial
Patients were randomly assigned in a 1:1 ratio to the mechanical thrombectomy alone group or the intravenous thrombolysis plus mechanical thrombectomy group using a permuted block design stratified by site. Each site was not required to provide screening logs during the recruitment phase. Thus, the number of patients assessed for eligibility is not available. ASPECTS indicates Alberta Stroke Program Early CT Score; mRS, modified Rankin Scale. aASPECTS too low indicates ASPECTS less than 5 on initial diffusion-weighted imaging or less than 6 on initial computed tomography.
Figure 2.
Figure 2.. Functional Outcomes at 90 Days From Onset According to the Modified Rankin Scale Score
Scores on the modified Rankin Scale range from 0 to 6, with 0 indicating no symptoms; 1, symptoms without clinical disability; 2, slight disability; 3, moderate disability; 4, moderately severe disability; 5, severe disability; and 6, death.
Figure 3.
Figure 3.. Subgroup Plot Showing the Adjusted Treatment Effect for Favorable Outcome, With P Values for Heterogeneity Across Subgroups
ASPECTS indicates Alberta Stroke Program Early CT Score; M1, middle cerebral artery M1 segment; and NIHSS, National Institutes of Health Stroke Scale. To convert glucose to mmol/L, multiply by 0.0555.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Jovin TG, Chamorro A, Cobo E, et al. ; REVASCAT Trial Investigators . Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372(24):2296-2306. doi:10.1056/NEJMoa1503780 - DOI - PubMed
    1. Berkhemer OA, Fransen PS, Beumer D, et al. ; MR CLEAN Investigators . A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20. doi:10.1056/NEJMoa1411587 - DOI - PubMed
    1. Campbell BC, Mitchell PJ, Kleinig TJ, et al. ; EXTEND-IA Investigators . Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009-1018. doi:10.1056/NEJMoa1414792 - DOI - PubMed
    1. Saver JL, Goyal M, Bonafe A, et al. ; SWIFT PRIME Investigators . Stent-retriever thrombectomy after intravenous t-PA vs t-PA alone in stroke. N Engl J Med. 2015;372(24):2285-2295. doi:10.1056/NEJMoa1415061 - DOI - PubMed
    1. Goyal M, Demchuk AM, Menon BK, et al. ; ESCAPE Trial Investigators . Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019-1030. doi:10.1056/NEJMoa1414905 - DOI - PubMed

MeSH terms

Substances