FOCUS
Efficacy and Safety of Monosialotetrahexosylganglioside as a Neuroprotective Agent in Patients with Acute Ischemic Stroke: A Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase 3 Trial
Year of Publication: 2023
PDF: Clinical Question
Does monosialotetrahexosylganglioside (GM1) improve functional outcomes in patients with acute ischemic stroke due to internal carotid artery occlusion when added to conventional therapy?
Study Overview
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
- Trial terminated early due to significant improvement in functional independence (mRS ≤2) at 90 days: 67.7% in GM1 group vs 57.5% in placebo group (p=0.0007)
- 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
Patients per Arm
601 in GM1 group, 602 in placebo group
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)
Design
Study Type: Randomized controlled trial
Randomization: 1
Blinding: Double-blind
Follow-up Duration: 90 days
Centers: 0
Countries:
Sample Size: 1203
Analysis: Interim analysis performed after 1,203 of 1,368 screened patients were randomized, leading to early termination
Inclusion Criteria
- Acute ischemic stroke attributable to internal carotid artery occlusion
- Symptom onset within 24 hours
- Baseline NIHSS score of 7-20
- Premorbid mRS score ≤1 in the event of recurrent AIS
Baseline Characteristics
| Characteristic | Control | Active |
|---|---|---|
| Note | Baseline characteristics were balanced between groups per trial description | Baseline characteristics were balanced between groups per trial description |
Arms
| Field | Control | GM1 |
|---|---|---|
| Intervention | Conventional therapy plus placebo daily for 12-14 days | Conventional therapy plus monosialotetrahexosylganglioside (GM1) 100 mg daily for 12-14 days |
| Duration | 12-14 days | 12-14 days |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Proportion of patients achieving modified Rankin Scale (mRS) ≤2 at 90 days | Primary | 57.5% | 67.7% | 10 | 0.0007 |
| mRS ≤1 at day 90 | Secondary | 0.0313 | |||
| mRS ≤1 at day 14 | Secondary | >0.05 | |||
| mRS ≤1 at day 30 | Secondary | >0.05 | |||
| Summary | Adverse | Incidence of adverse events was similar between groups | |||
| Treatment-emergent adverse events | Adverse | None reported | |||
| Guillain-Barré syndrome | Adverse | No cases reported in either group |
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
Based on: FOCUS (2023)
Content summarized and formatted by NeuroTrials.ai.