The DIAS study (Part 2) was performed to support the dose finding of desmoteplase treatment in subjects with acute ischemic stroke selected by perfusion/diffusion mismatch on MRI within a time window of 3 to 9 h after stroke-symptom onset. In addition, it assessed safety and tolerability of 3 doses of desmoteplase compared with placebo with special consideration of intracranial hemorrhage and major systemic bleedings.
Acute stroke is the third leading cause of mortality in developed countries and the major medical cause of disability. The outcome can be improved by early treatment with thrombolysis. Alteplase (r-tPA) is the only approved thrombolytic drug in the indication of acute ischemic stroke. However, the use of alteplase is currently restricted by the need to administer it within 3 hours of symptom onset. As the risk of transforming a cerebral infarct into haemorrhage probably rises as the time elapsed increases, a thrombolytic drug that carries a lower risk of haemorrhage than alteplase may offer a wider time-to-treatment window and improve the safety profile.Desmoteplase (DSPA) with its high fibrin specificity, lack of neurotoxicity, potential neuroprotective effect, non-activation by ß-amyloid, and long terminal half-life may account for an improved safety and efficacy profile within the first 9 hours after onset of symptoms.
- Desmoteplase Drug
Intervention Desc: Desmoteplase 125 µg/kg BW ARM 1: Kind: Experimental Label: 1 Description: Desmoteplase 62.5 µg/kg BW i.v. bolus ARM 2: Kind: Experimental Label: 2 Description: Desmoteplase 90 µg/kg BW i.v. bolus ARM 3: Kind: Experimental Label: 3 Description: Desmoteplase 125 µg/kg BW i.v. bolus
- Placebo Drug
Intervention Desc: Placebo ARM 1: Kind: Experimental Label: 4 Description: Placebo i.v. bolus
- Allocation: Randomized
- Masking: Double Blind (Subject, Caregiver, Investigator)
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||National Institutes of Health Stroke Scale (NIHSS), Barthel-Index & mRS||Day 90||No|
|Primary||Change in lesion volume||Day 30||No|
|Secondary||Reperfusion after 4-8 h||8 h||No|
|Secondary||Safety and pharmacoeconomic outcomes||Day 90||No|