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

Abstract

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.

Figure 1.. Study Flowchart

mITT indicates modified intention-to-treat; mRS, modified Rankin Scale (higher scores indicate worse function); NIHSS, National Institutes of Health Stroke Scale (higher scores indicate more severe stroke).

Figure 2.. Distribution of the Modified Rankin Scale (mRS) Scores on Day 90

Scores range from 0 (no neurologic deficit, no symptoms, or completely recovered) to 6 (death). ITT indicates intention to treat.

Figure 3.. Prespecified Subgroup Analysis of the Primary Outcome

The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin Scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. BMI indicates body mass index (calculated as the weight in kilograms divided by the height in meters squared); LAA, large artery atherosclerosis; OR, odds ratio; SAO, small-artery occlusion; and TOAST, Trial of Org 10172 in Acute Stroke Treatment.