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Randomized Controlled Trial
. 2023 Aug 1;80(8):851-859.
doi: 10.1001/jamaneurol.2023.1871.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial

Collaborators, Affiliations
Randomized Controlled Trial

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial

Anxin Wang et al. JAMA Neurol. .

Abstract

Importance: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown.

Objective: To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment.

Design, setting, and participants: This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022.

Interventions: Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio.

Main outcomes and measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity.

Results: Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group.

Conclusions and relevance: Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo.

Trial registration: ClinicalTrials.gov Identifier: NCT03539445.

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Conflict of interest statement

Conflict of Interest Disclosures: None disclosed.

Figures

Figure 1.
Figure 1.. Flowchart of the Study
NIHSS indicates National Institute of Health Stroke Scale; rt-PA, recombinant tissue plasminogen activator.
Figure 2.
Figure 2.. Distribution of 90-Day Modified Rankin Scale (mRS) Score by Treatment Group and Baseline Stroke Severity
The mRS is a global stroke disability scale with scores ranging from 0 (no symptoms or completely recovered) to 6 (death). The diagonal line between the 2 study groups indicates the dichotomization of a favorable functional outcome in each severity stratum. Favorable functional outcome was defined as an mRS score of 0 in patients with a baseline National Institutes of Health Stroke Scale (NIHSS) score of 4 to 7; an mRS score of 0 to 1 in patients with a baseline NIHSS score of 8 to 14; and an mRS score of 0 to 2 in patients with a baseline NIHSS score of 15 to 25.
Figure 3.
Figure 3.. Odds Ratio for the Primary Outcome in Prespecified Subgroups
EVT indicates endovascular treatment; LACI, lacunar infarcts; NIHSS, National Institute of Health Stroke Scale; OCSP, Oxfordshire Community Stroke Project; PACI, partial anterior circulation infarcts; POCI, posterior circulation infarcts; rt-PA, recombinant tissue plasminogen activator; TACI, total anterior circulation infarcts.

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