• Hui-Sheng Chen, Yu Cui, Zhong-He Zhou, Ying-Jie Dai, Gao-Hua Li, Zhao-Long Peng, Yi Zhang, Xiao-Dong Liu, Zhi-Mei Yuan, Chang-Hao Jiang, Qing-Cheng Yang, Ying-Jie Duan, Guang-Bin Ma, Li-Wei Zhao, Rui-Xian Wang, Yuan-Lin Sun, Lei Shen, Er-Qiang Wang, Li-Hua Wang, Ye-Fang Feng, Feng-Yun Wang, Ren-Lin Zou, He-Ping Yang, Kai Wang, Duo-Lao Wang, Yi-Long Wang, and ARAIS Investigators.
• Department of Neurology, General Hospital of Northern Theatre Command, Shenyang, China.
• JAMA. 2023 Feb 28; 329 (8): 640650640-650.

ImportancePrevious studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking.ObjectiveTo assess the efficacy of argatroban plus alteplase for AIS.Design, Setting, And ParticipantsThis multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022.InterventionsEligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 μg/kg bolus over 3-5 minutes followed by an infusion of 1.0 μg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments.Main Outcomes And MeasuresThe primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set.ResultsAmong 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group.Conclusions And RelevanceAmong patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days.Trial RegistrationClinicalTrials.gov Identifier: NCT03740958.

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