Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset.
OBJECTIVE
Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke.


METHODS
DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 microg/kg and 125 microg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined.


RESULTS
Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 microg/kg: n=14; 125 microg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 microg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 microg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 microg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 microg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 microg/kg desmoteplase (P=0.022).


CONCLUSIONS
Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 microg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).
Furlan
Anthony J
AJ
Department of Neurology, The Cleveland Clinic, Cleveland, OH 44195, USA. furlana@ccf.org
Eyding
Dirk
D
Albers
Gregory W
GW
Al-Rawi
Yasir
Y
Lees
Kennedy R
KR
Rowley
Howard A
HA
Sachara
Christian
C
Soehngen
Mariola
M
Warach
Steven
S
Hacke
Werner
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000707:Anaphylaxis / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005858:Germany; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009316:National Institutes of Health (U.S.); D010960:Plasminogen Activators / Q000008:administration & dosage* / Q000009:adverse effects; D015424:Reperfusion; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D005343:Fibrinolytic Agents; C069588:salivary plasminogen activator alpha 1, Desmodus rotundus; D010960:Plasminogen Activators