HONOLULU—A phase III trial shows no evidence that DP-b99 provides benefits for patients with acute ischemic stroke when administered within nine hours of symptom onset, according to research presented at the 2013 International Stroke Conference. The distribution of modified Rankin Scale scores did not differ between patients who received DP-b99 and those who received placebo, and adjustment for baseline age and NIH Stroke Scale (NIHSS) score did not alter this result.
An Investigation of Positive Phase II Results
After a phase II trial suggested that DP-b99 could improve modified Rankin scores, particularly for patients with moderate to severe stroke, Kennedy Lees, MD, and colleagues designed a phase III trial to test this hypothesis. The investigators planned to select 770 patients with ischemic stroke, NIHSS scores between 10 and 16, and cortical stroke findings because DP-b99 had had the greatest effect in this population in the phase II trial.
The primary outcome was the ordinal analysis of modified Rankin scores. The investigators planned to perform an interim analysis after half of the patients had been enrolled. If an independent data monitoring committee determined that the chance of a positive result was less than 20%, the investigators agreed to abandon the trial.
Outcomes Were Slightly Better for the Control Group
Dr. Lees, a Professor of Cerebrovascular Medicine at the University of Glasgow, and colleagues randomized 446 patients to DP-b99 or placebo. Of these patients, 350 had been randomized and followed up by the time of the interim analysis, which indicated the trial’s futility. In the modified intent-to-treat population, patients had to have at least one outcome measure at any time after baseline.
A total of 218 patients received DP-b99, and 219 received placebo. In general, the two study groups were balanced, but the placebo group was three years younger, on average, and had a lower proportion of previous stroke than the treatment group, said Dr. Lees.
Nearly 21% of patients who received DP-b99 recovered to a modified Rankin score of 1 or lower, compared with almost 29% of patients who received placebo. Approximately 19% of patients who received DP-b99 attained an NIHSS score of 1 or lower, compared with nearly 26% of control patients.
Mortality was 16.5% among patients who received DP-b99 and 15.1% among patients who received placebo. The number of days (of the first 90 days) that patients spent at home was not changed by treatment. The primary, secondary, and safety outcomes give “no indication of any positive effect” of the drug, said Dr. Lees. A subgroup analysis did not change the investigators’ interpretation of the results.
—Erik Greb
Senior Associate Editor
Suggested Reading
Lees KR, Bornstein N, Diener HC, et al. Results of Membrane-Activated Chelator Stroke Intervention Randomized Trial of DP-b99 in acute ischemic stroke. Stroke. 2013 Feb 7 [Epub ahead of print].
Rosenberg G, Bornstein N, Diener HC, et al. The Membrane-Activated Chelator Stroke Intervention (MACSI) Trial of DP-b99 in acute ischemic stroke: a randomized, double-blind, placebo-controlled, multinational pivotal phase III study. Int J Stroke. 2011;6(4):362-367.