Study of Desmoteplase (International Nonproprietary Name [INN]) in Acute Ischemic Stroke (DIAS-2)

Completed

Phase 3 Results

Results

At 90-day follow up, 47.4% of patients treated with 90 mcg/kg Desmoteplase and 36.4% of patients treated with 125 mcg/kg Desmoteplase, compared to 46.0% in the placebo group with neither dose of Desmoteplase were responders (patients who improved by >/=8 NIHSS points, had a modified Rankin score of 0 to 2, and a Barthel index score of 75-100). Mortality rate 90-day follow up was 4 in the placebo group, 3 in the 90 mcg/kg dose group and 14 in the 125 mcg/kg dose group (10 of the 14 were considered by the investigators as not related to the drug, 9 of which occurred 14 or more days after stroke and were from non-neurological causes). The rate of symptomatic intracranial bleeding within 72 hours after study drug administration was 0% in the placebo group, 3.5% in the 90 mcg/kg dose group and 4.5% in the 125 mcg/kg group. Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 ?g/kg desmoteplase; 66 received 125 ?g/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6—14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10·6 cm3 and 52·5 cm3, respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 ?g/kg desmoteplase, 36% (24 of 66) for 125 ?g/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 ?g/kg desmoteplase 14·0% (0·5 cm3); 125 ?g/kg desmoteplase 10·8% (0·3 cm3); placebo ?10·0% (?0·9 cm3). The rates of symptomatic intracranial haemorrhage were 3·5% (2 of 57) for 90 ?g/kg desmoteplase, 4·5% (3 of 66) for 125 ?g/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% [3 of 57] for 90 ?g/kg desmoteplase; 21% [14 of 66] for 125 ?g/kg desmoteplase; and 6% [4 of 63] for placebo). The DIAS-2 study did not show a benefit of desmoteplase given 3—9 h after the onset of stroke. The high response rate in the placebo group could be explained by the mild strokes recorded (low baseline NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase.