The Desmoteplase in Acute Ischemic Stroke (DIAS) clinical trial program.

BACKGROUND: Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in phase III of clinical development. In comparison to alteplase, it has high fibrin selectivity, is associated with minimal or no neurotoxicity, and has no apparent negative effect on the blood-brain barrier. The safety and efficacy of desmoteplase is being studied in the Desmoteplase in Acute Ischemic Stroke clinical trial program. Three studies (Dose Escalation Study of Desmoteplase in Acute Ischemic Stroke, Desmoteplase in Acute Ischemic Stroke, and Desmoteplase in Acute Ischemic Stroke-2) have been completed, two large randomized, double-blind, placebo-controlled, phase III trials are ongoing at >200 sites worldwide (Desmoteplase in Acute Ischemic Stroke-3 and Desmoteplase in Acute Ischemic Stroke-4, n = 800; DIAS-3 and DIAS-4), and a randomized, double-blind, placebo-controlled, dose-escalation phase II trial is ongoing in Japan (Desmoteplase in Acute Ischemic Stroke-Japan, n = 48; DIAS-J).

AIMS: The objective of DIAS-3 and DIAS-4 is to evaluate the safety and efficacy of a single IV bolus injection of 90 μg/kg desmoteplase given three- to nine-hours after onset of ischemic stroke (National Institutes of Health Stroke Scale 4-24, age 18-85 years). The objective of DIAS-J is to evaluate the safety and tolerability of desmoteplase 70 and 90 μg/kg three- to nine-hours after ischemic stroke onset in Japanese patients.

METHODS: Patients are included with occlusion or high-grade stenosis (thrombolysis in myocardial infarction 0-1) in proximal cerebral arteries on magnetic resonance or computed tomography angiography but excluded with extended ischemic edema on computed tomography or diffusion-weighted imaging.

CONCLUSION: Desmoteplase is the only thrombolytic agent in late-stage development for acute ischemic stroke that is now tested in patients with proven stroke pathology. The results of the Desmoteplase in Acute Ischemic Stroke clinical trial program will show whether patients with major artery occlusions but not extended ischemic brain damage can be safely and effectively treated up to nine-hours after onset.