CHARM
(2024)Objective
To assess whether intravenous glibenclamide could improve functional outcome at 90 days in patients with large hemispheric infarction at risk of cerebral edema
Study Summary
• Enrolled 535 patients aged 18-85 years with large hemispheric stroke (ASPECTS 1-5 or ischemic core 80-300 mL)
• Trial stopped early for strategic and operational reasons (slow enrollment due to COVID-19) before unblinding
Intervention
Intravenous glibenclamide 8.6 mg over 72 hours versus placebo, started within 10 hours of stroke onset
Inclusion Criteria
Age 18-85 years, large stroke defined by ASPECTS 1-5 or ischemic core lesion volume 80-300 mL on CT perfusion or MRI DWI
Study Design
Arms: Glibenclamide versus Placebo
Patients per Arm: 217 glibenclamide, 214 placebo (mITT population aged 18-70 years)
Outcome
• 90-day mortality: 32% glibenclamide vs 29% placebo (HR 1.20, 95% CI 0.85-1.70, p=0.30)
• Hypoglycemia occurred in 6% of glibenclamide group vs 2% of placebo group
Bottom Line
Intravenous glibenclamide did not improve functional outcomes at 90 days in patients with large hemispheric infarction, although the trial was stopped early and underpowered to make definitive conclusions.
Major Points
- First phase 3 trial evaluating glibenclamide for prevention of cerebral edema after large hemispheric stroke
- Trial stopped early by sponsor for strategic and operational reasons (slow enrollment due to COVID-19) before unblinding
- No significant improvement in 90-day functional outcome measured by modified Rankin Scale shift (common OR 1.17, 95% CI 0.80-1.71, p=0.42)
- 90-day mortality trended higher in glibenclamide group (32% vs 29%) but not statistically significant
- Hypoglycemia was more common in glibenclamide group (6% vs 2%)
- Study underpowered due to early termination, limiting definitive conclusions
Study Design
- Study Type
- Phase 3, randomized controlled trial
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 535
- Follow-up
- 90 days
- Centers
- 143
- Countries
- 21 countries
Primary Outcome
Definition: Shift in distribution of scores on modified Rankin Scale at day 90
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Not specified | Not specified | - (0.80-1.71) | 0.42 |
Limitations & Criticisms
- Trial stopped early by sponsor for strategic and operational reasons, resulting in underpowered study
- Slow enrollment attributed to COVID-19 pandemic
- Sample size insufficient to make definitive conclusions about efficacy
- Exclusion criteria not fully detailed in abstract
- Age restriction to 18-70 years for primary analysis may limit generalizability
- Study drug initiated relatively late (mean ~9 hours after stroke onset)
Citation
Lancet Neurol. 2024;23:1205-13