• Cerebrovascular Disease Clinical Trials
• Interventional Techniques & Devices
• Ischemia

The Evaluating Neuroprotection in Aneurysm Coiling Therapy trial [ENACT; NCT00728182] showed that the novel agent NA-1 may be a useful treatment for stroke and ruptured aneurysm patients. Michael D. Hill, MD, MSc, FRCPC, University of Calgary, Calgary, Alberta, Canada, reported outcomes from the study.

A randomized, multicenter, double-blind, placebo-controlled, single-dose Phase 2 trial, ENACT randomized 197 male and female patients who were undergoing endovascular repair of a brain aneurysm to receive 2.6 mg/kg of NA-1 (n=92), a peptide designed to reduce ischemic brain damage, or placebo (n=93) as a 10-minute intravenous infusion after completion of the endovascular procedure on Day 1.

The primary outcome measures were to determine the safety and tolerability of a single IV dose of NA-1 in patients who were undergoing endovascular repair of brain aneurysms and establish the efficacy of NA-1 in reducing the volume of embolic strokes on enrollment and Days 1, 2–4, and 30. Secondary outcome measures were to determine the efficacy of a single IV dose of NA-1 in reducing the number of embolic strokes, procedurally induced vascular cognitive impairment, and frequency of large strokes on enrollment and Days 1, 2–4, and 30.

Other than the number of past smokers (26.9% in controls versus 43.8% in the treatment group), baseline characteristics and treatment factors were similar between the two groups. Except for 2 adverse events of transient (15 minutes) mild hypotension, no serious adverse events were attributable to NA-1.

Compared with baseline, the number and volume reductions of diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) lesions in all subjects were significant (p=0.005 and p=0.026, respectively). In ruptured aneurysm patients, significant reductions in the number of DWI and FLAIR lesions were observed in the treatment and control groups (unadjusted p=0.027 and p=0.46, respectively); similarly, there were significant reductions in the volume of DWI and FLAIR lesions (unadjusted p=0.015 and p=0.023, respectively). In unruptured aneurysm subjects, there were significant reductions between the treatment and control groups in the number of DWI lesions (adjusted p=0.019).

In patients without large stroke, there were significant reductions in the number of DWI and FLAIR lesions (adjusted p=0.002 and p=0.012, respectively) as well as in volume (p=0.009 and p=0.014, respectively). Among proportions of patients with DWI lesions, binned at the 90^th percentile, more NA-1 subjects had 0 or 1 lesions; fewer had >15 lesions (p=0.012). Among subjects with ruptured aneurysms, 68.4% of controls and 100% of the treatment group had an NIHSS of 0 to 1 (p=0.020); 73.7% of controls and 94.4% of the treatment group had a modified Rankin scale score of 0 to 2. The relative risk was 1.3 (95% CI, 0.95 to 1.7; p=0.180).

Overall, the trial showed that NA-1 was safe in patients with ruptured and unruptured aneurysms and reduced the number and volume of ischemic stroke lesions in a human model of iatrogenic embolic stroke. The study implies that neuroprotection is possible in older patients and that multiple endovascular procedures may be amenable to NA-1 treatment for stroke.

The authors concluded that testing of NA-1 in human community-acquired stroke is a priority and that it may be a useful treatment for ruptured aneurysm patients.

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The editors would like to thank the many members of the International Stroke Conference 2012 presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.

• © 2012 MD Conference Express®