Background and purpose: Desmoteplase is a novel and highly fibrin-specific thrombolytic agent. Evidence of safety and efficacy was obtained in 2 phase II trials (Desmoteplase In Acute Ischemic Stroke [DIAS] and Desmoteplase for Acute Ischemic Stroke [DEDAS]). The DIAS-2 phase III trial did not replicate the positive phase II efficacy findings. Post hoc analyses were performed with the aim of predicting treatment responders based on CTA and MRA.
Methods: Patients were grouped according to vessel status (Thrombolysis In Myocardial Infarction [TIMI] grade) for logistic regression of clinical response, applying the data from DIAS-2 as well as the pooled data from DIAS, DEDAS, and DIAS-2.
Results: In DIAS-2, a substantial number of mismatch-selected patients (126/179; 70%) presented with a normal flow/low-grade stenosis (TIMI 2-3) at screening, with the majority having a favorable outcome at day 90. In contrast, favorable outcome rates in patients with vessel occlusion/high-grade stenosis (TIMI 0-1) were 18% with placebo versus 36% and 27% with desmoteplase 90 and 125 μg/kg, respectively. The clinical effect based on the pooled data from DIAS, DEDAS, and DIAS-2 was favorable for desmoteplase-treated patients presenting with TIMI 0 to 1 at baseline (OR, 4.144; 95% CI, 1.40-12.23; P=0.010). There was no desmoteplase treatment benefit in patients presenting with TIMI 2 to 3 (OR, 1.109).
Conclusions: In this sample of patients with a mismatch diagnosed, proximal vessel occlusion or severe stenosis was associated with clinically beneficial treatment effects of desmoteplase. Selecting patients using CTA or MRA in clinical trials of thrombolytic therapy is justifiable.
Trial registration: ClinicalTrials.gov NCT00111852 NCT00638248 NCT00638781.