FOCUS
(2023)Objective
To evaluate the efficacy and safety of monosialotetrahexosylganglioside (GM1) as a neuroprotective agent in patients with acute ischemic stroke attributable to internal carotid artery occlusion
Study Summary
• GM1 demonstrated a favorable safety profile with no significant differences in adverse events between groups
Intervention
GM1 (monosialotetrahexosylganglioside) 100 mg daily for 12-14 days plus conventional therapy versus placebo plus conventional therapy
Inclusion Criteria
Acute ischemic stroke attributable to internal carotid artery occlusion, symptom onset within 24 hours, baseline NIHSS score 7-20, premorbid mRS ≤1 (if recurrent AIS)
Study Design
Arms: GM1 group (conventional therapy + GM1 100 mg daily) versus Placebo group (conventional therapy + placebo)
Patients per Arm: 601 in GM1 group, 602 in placebo group
Outcome
• Secondary outcome: GM1 group showed superiority for mRS ≤1 at day 90 (RD 6.63%, p=0.0313)
• No significant improvements in mRS ≤1 at days 14 and 30
• Similar adverse event rates between groups with no treatment-emergent adverse events including Guillain-Barré syndrome
Bottom Line
In patients with acute ischemic stroke due to internal carotid artery occlusion, GM1 100 mg daily for 12-14 days significantly improved functional independence at 90 days (mRS ≤2: 67.7% vs 57.5%, p=0.0007) compared to placebo, with a favorable safety profile, leading to early trial termination.
Major Points
- Trial was terminated early due to significant benefit in the primary endpoint
- GM1 improved functional independence (mRS ≤2) at 90 days with an absolute risk difference of 10.16% (NNT approximately 10)
- GM1 showed superiority for excellent functional outcome (mRS ≤1) at day 90 but not at earlier timepoints (days 14 and 30)
- No safety concerns were identified, with similar adverse event rates between groups and no cases of Guillain-Barré syndrome
- Study specifically targeted patients with internal carotid artery occlusion with moderate to severe strokes (NIHSS 7-20)
Study Design
- Study Type
- Randomized controlled trial
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 1203
- Follow-up
- 90 days
Primary Outcome
Definition: Proportion of patients achieving modified Rankin Scale (mRS) ≤2 at 90 days
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 57.5% | 67.7% | - (98.78% CI 2.70%-17.61%) | 0.0007 |
Limitations & Criticisms
- Early termination may overestimate treatment effect
- Lack of detailed baseline characteristics provided in the summary
- No information on adjunctive therapies (e.g., thrombolysis, thrombectomy rates)
- Unknown if results are generalizable beyond internal carotid artery occlusion
- Limited information on long-term outcomes beyond 90 days
- No detailed safety data or specific adverse event rates provided