Safety and Efficacy of a New Thrombolysis Dosing Regimen - Pilot Study

Objective: The main limitations of the treatment with tissue plasminogen activator (tPA) include low recanalization efficacy and the risk of intracerebral hemorrhage. The aim of this study was to test new dosing of intravenous tPA. Methodology: This is a prospective, non-randomized open-label study with 3 groups of patients (n = 12) with acute ischemic stroke due to artery occlusion. Three dosing regimes of tPA were: 0.8 mg/kg/60 min; 1.0 mg/kg/90 min, and 1.2 mg/kg/120 min. During treatment, recanalization was monitored with transcranial color-coded sonography (TCCD). Thrombolytic treatment was to be if full recanalization was diagnosed. The primary safety endpoint was the incidence of sICH within 36 hours. The main efficiency endpoint was the rate of complete recanalization at 120 minutes after treatment initiation. Results: In the 0.8 mg/kg dose group, no recanalization was achieved in the first six patients and, therefore, recruitment was stopped due to a lack of efficacy. In the 1.0 mg/kg/90 min and 1.2 mg/kg/120 min groups, 12 patients were enrolled. In each of these cohorts, one complete recanalization was achieved and one sICH was diagnosed. In two patients (in the 1.2 mg/kg group), treatment was terminated after recanalization within 30 minutes but reocclusion occurred in one of them. Favorable outcome at three months was predicted by the baseline NIHSS (OR 0.6, 95% CI 0.4-0.9) and systolic flow velocity in the affected artery at 120th minute (OR 1.1, 95% CI 1.01-1.2). Conclusions: The aim of tPA treatment is to achieve adequate flow velocity in the affected artery but this objective was not achieved by a different tPA dosing.