PDF: BAST
(2023)Objective
To assess the efficacy and safety of the neuroprotective agent DL-3-n-butylphthalide (NBP) in acute ischemic stroke patients receiving reperfusion therapy (intravenous thrombolysis and/or endovascular treatment).
Study Summary
• Patients were randomized to a 90-day course of the neuroprotective agent NBP or placebo, administered adjunctively to standard reperfusion therapy.
• NBP treatment resulted in a significantly higher proportion of patients with a favorable functional outcome at 90 days compared to placebo (56.7% vs. 44.0%; p<0.001).
• The rate of serious adverse events was similar between the two groups.
Intervention
A 90-day course of DL-3-n-butylphthalide (NBP) (14 days intravenous followed by 76 days oral) or placebo, initiated within 6 hours of stroke onset in patients undergoing reperfusion therapy.
Study Design
Arms: Butylphthalide (NBP): 14 days IV then 76 days oral (n=527) vs Placebo (n=525)
Outcome
• Safety was comparable, with serious adverse events within 90 days occurring in 10.1% of the NBP group and 12.0% of the placebo group.
Bottom Line
Among patients in China with acute ischemic stroke receiving reperfusion therapy, treatment with the neuroprotective agent butylphthalide (NBP) for 90 days was associated with a significantly higher proportion of patients achieving a favorable functional outcome at 90 days compared to placebo, with a similar safety profile.
Major Points
- This was a large, multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 59 centers in China.
- The trial enrolled 1216 patients with acute ischemic stroke (NIHSS score 4-25) who were treated within 6 hours of onset and were receiving either intravenous thrombolysis, endovascular treatment, or both.
- Patients were randomized 1:1 to receive NBP or placebo for a total of 90 days (14 days of intravenous followed by 76 days of oral therapy).
- The primary outcome was a favorable functional outcome at 90 days, defined by a modified Rankin Scale (mRS) score threshold that was adjusted based on the patient's baseline stroke severity.
- A significantly higher proportion of patients in the NBP group achieved a favorable outcome: 56.7% vs. 44.0% in the placebo group (Odds Ratio, 1.70; 95% CI, 1.35-2.14; P<.001).
- The rate of serious adverse events within 90 days was not significantly different between the groups (10.1% in the NBP group vs. 12.0% in the placebo group).
Study Design
- Study Type
- Multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial
- Randomization
- Yes
- Blinding
- Double-blind (researchers and patients)
- Sample Size
- 1216
- Follow-up
- 90 days
- Centers
- 59
- Countries
- China
Primary Outcome
Definition: Proportion of patients with a favorable functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 0 for baseline NIHSS 4-7; mRS 0-1 for baseline NIHSS 8-14; and mRS 0-2 for baseline NIHSS 15-25.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 44.0% (268/609) | 56.7% (344/607) | - (1.35-2.14) | <.001 |
Limitations & Criticisms
- The proportion of patients receiving endovascular treatment was relatively small (~30%), which may limit the generalizability of the findings to populations with higher rates of thrombectomy.
- The trial was conducted exclusively in China, and the findings may not be generalizable to other ethnic or geographic populations.
- The study enrolled a large number of patients with mild stroke (low NIHSS score), which contributed to lower overall rates of mortality and symptomatic intracranial hemorrhage than seen in other reperfusion trials.
- The use of small block sizes for randomization might have increased the risk of a predictable allocation process.
Citation
JAMA Neurol. 2023;80(8):851-859.