PDF: SONIC
(2022)Objective
To evaluate the safety and efficacy of the neuroprotectant nelonemdaz in patients with acute large vessel occlusion stroke undergoing endovascular reperfusion therapy.
Study Summary
• Patients were randomized 1:1:1 to receive a 5-day course of placebo, low-dose nelonemdaz, or high-dose nelonemdaz.
• There was no statistically significant difference in the primary outcome of good functional outcome (modified Rankin Scale score of 0-2) at 12 weeks among the three groups.
• The drug was safe, with no serious adverse events. There was a non-significant trend toward better outcomes with nelonemdaz, warranting a larger trial.
Intervention
A 5-day intravenous course of low-dose nelonemdaz (2750 mg total), high-dose nelonemdaz (5250 mg total), or placebo, initiated prior to thrombectomy for acute large vessel occlusion stroke. Follow-up was for 12 weeks.
Study Design
Arms: Array
Outcome
• No serious adverse events were reported, and the overall rate of adverse events was similar across groups.
• There was a statistically significant improvement in the Barthel Index (>90) for the high-dose group compared to placebo (p=0.0480).
Bottom Line
In this phase II trial, adjunctive treatment with nelonemdaz did not result in a statistically significant improvement in the proportion of patients with a good functional outcome at 12 weeks compared to placebo. However, the treatment was safe and showed a favorable, non-significant trend toward better outcomes, warranting a larger phase III trial.
Major Points
- SONIC was a multicenter, randomized, double-blind, placebo-controlled, 3-arm, phase II trial conducted at 7 centers in South Korea.
- 209 patients with acute ischemic stroke due to large-vessel occlusion undergoing endovascular therapy within 8 hours of onset were randomized 1:1:1 to receive placebo, low-dose nelonemdaz (2750 mg total), or high-dose nelonemdaz (5250 mg total).
- The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0-2 at 12 weeks.
- The primary outcome did not differ significantly among the groups: 54.1% in the placebo group, 61.5% in the low-dose group, and 63.2% in the high-dose group (P=0.5578).
- No serious adverse events related to the drug were reported, and the overall frequency of adverse events was similar across all groups.
- A favorable, though not statistically significant, shift in the distribution of mRS scores at 12 weeks was observed in the nelonemdaz treatment groups compared to placebo.
Study Design
- Study Type
- Multicenter, randomized, double-blind, placebo-controlled, 3-arm, phase II clinical trial
- Randomization
- Yes
- Blinding
- Double-blind (study investigators and participants blinded to treatment allocation)
- Sample Size
- 209
- Follow-up
- 12 weeks
- Centers
- 7
- Countries
- South Korea
Primary Outcome
Definition: The proportion of patients with a modified Rankin Scale (mRS) score of 0-2 at 12 weeks.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 54.1% (33/61) | 61.5% (40/65) for low-dose; 63.2% (36/57) for high-dose | - | 0.5578 |
Limitations & Criticisms
- The trial did not demonstrate a statistically significant benefit for its primary endpoint.
- A high dropout rate resulted in a smaller full analysis set (183/208) than planned, potentially reducing statistical power.
- There were baseline imbalances between groups; the low-dose group was younger and had a higher rate of intravenous alteplase use, which may have biased results.
- The P value for statistical significance was set at an unconventional level of ≤0.1.
Citation
https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.122.039649