Tongxinluo and Functional Outcomes Among Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Dong, Yi; Jiang, Kaifu; Li, Zhenguang; Zhou, Yanhua; Ju, Bo; Min, Lianqiu; He, Qiu; Fan, Ping; Hu, Wenli; Qu, Hongdang; Wu, Haiqin; Pan, Chunlian; Cao, Yibing; Lou, Xiaoliang; Zhang, Guiru; Zhang, Jiewen; Hu, Fengyun; Dong, Qiang

Key Points: Question: Can the antioxidant drug Tongxinluo, which consists of 12 traditional Chinese herbs and medicines, improve short-term functional outcomes in patients with acute ischemic stroke? Findings: In this randomized clinical trial that included 2007 participants with acute ischemic stroke randomized within 72 hours of symptom onset, oral administration of Tongxinluo for 90 days compared with placebo significantly improved the rate of favorable functional outcome (modified Rankin Scale score, 0 or 1) at 90 days. Meaning: Among patients with acute mild-to-moderate ischemic stroke, Tongxinluo given within 72 hours of symptom onset improved clinical outcomes at 90 days; further research is needed to explore this outcome. Importance: Previous studies revealed limited effectiveness of neuroprotective agents in treating acute ischemic stroke (AIS). Tongxinluo, developed from traditional Chinese medicines, has been recognized as a novel neuroprotective agent with anti-inflammatory properties that stabilize vulnerable plaques in animal models and patients with myocardial infarction. Objective: To assess the efficacy and safety of Tongxinluo in patients with acute ischemic stroke (AIS). Design, Setting, and Participants: This multicenter, open-label, double-blind, randomized clinical trial included 2007 patients with AIS and a National Institutes of Health Stroke Scale score between 4 and 22 at admission. The trial was conducted at 50 hospitals in China from March 1, 2014, to October 31, 2016. Data were analyzed from November 14, 2016, to November 16, 2017. Interventions: Eligible patients were randomized within 72 hours of symptom onset to the Tongxinluo group or the control group. Participants received 4 oral capsules of Tongxinluo or placebo, 3 times a day for 90 days. Other treatment was administrated according to guidelines. Main Outcomes and Measure: The primary outcome was a favorable functional outcome at day 90 after randomization, defined as a modified Rankin Scale (mRS) score of 0 to 1 (on a scale of 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]). All statistical analyses were performed in a modified intention-to-treat population, defined as all patients who underwent randomization, were given any treatment, and underwent any posttreatment assessment. Results: Among 2007 patients with AIS who were randomized, 1946 (96.5%) were included in the modified intention-to-treat analysis (973 in the Tongxinluo group and 973 in the control group, with mean [SD] age of 60.5 [9.2] years and 1342 [69.0%] male). Patients in the Tongxinluo group had a significantly higher proportion of favorable functional outcomes at day 90 compared with those in the control group (mRS score of 0-1, 640 [65.8%] vs 575 [59.1%]; odds ratio, 1.33 [95% CI, 1.11-1.60]; P =.002). The prespecified subgroup analyses indicated that, among all subgroups, additional Tongxinluo treatment had similar outcomes. Conclusions and Relevance: Among patients with ischemic stroke within 72 hours after symptom onset, those additionally receiving Tongxinluo were more likely to have a favorable functional outcome, compared with a placebo group. Further research in patients with thrombolysis and endovascular treatment are needed to explore these outcomes. Trial registration: ClinicalTrials.gov Identifier: NCT01919671 This randomized clinical trial investigates the effects of a traditional Chinese medicine formulation (Tongxinluo) compared with placebo on functional outcome in patients with acute ischemic stroke.

CHINA; CHINESE medicine; NEUROPROTECTIVE agents; ANTI-inflammatory agents; NIH Stroke Scale; PATIENT safety; RESEARCH funding; HERBAL medicine; STATISTICAL sampling; BLIND experiment; LOGISTIC regression analysis; FUNCTIONAL status; TREATMENT effectiveness; RANDOMIZED controlled trials; ORAL drug administration; DESCRIPTIVE statistics; ODDS ratio; DRUG efficacy; ISCHEMIC stroke; RESEARCH; CONFIDENCE intervals; DATA analysis software; PHARMACEUTICAL encapsulation; DRUG dosage; THERAPEUTICS; EVALUATION; DRUG administration

JAMA Network Open, 2024, Vol 7, Issue 9, pe2433463

2574-3805

Academic Journal

10.1001/jamanetworkopen.2024.33463