AIM: We performed an open-label, dose-ascending, single-centre, Phase IIa study to explore the safety and efficacy of catheter-directed thrombolysis (CDT) with microplasmin for infrainguinal arterial or bypass occlusions. METHODS: Patients who presented with acute occlusions were subsequently treated with an intrathrombus infusion of five ascending doses of microplasmin: 0.3 mg/kg/h for 4 hours; 0.45 mg/kg/h for 4 hours; 0.6 mg/kg/h for 4 hours; 0.9 mg/kg/h for 4 hours or 0.6 mg/kg/h for 6 hours. Repeat angiograms were obtained to assess the degree of clot lysis. The primary outcome was complete thrombolysis defined as >95% thrombus volume reduction at the end of the microplasmin infusion. Safety evaluation included bleedings, adverse events and coagulation biomarkers. RESULTS: Complete thrombolysis was obtained in 3 of the 19 treated patients at the end of microplasmin infusion. Thrombus volume reduction between 50% and 95% was achieved with all dosing regimens. Clinically significant distal embolization occurred in 8 patients. One major and two non-major bleedings occurred. Microplasmin depleted α2-anti-plasmin and decreased fibrinogen. CONCLUSION: Intrathrombus infusion of microplasmin for 4 or 6 hours resulted in significant clot lysis. Distal embolization appeared the most important limitation.
AIM: We performed an open-label, dose-ascending, single-centre, Phase IIa study to explore the safety and efficacy of catheter-directed thrombolysis (CDT) with microplasmin for infrainguinal arterial or bypass occlusions. METHODS:Patients who presented with acute occlusions were subsequently treated with an intrathrombus infusion of five ascending doses of microplasmin: 0.3 mg/kg/h for 4 hours; 0.45 mg/kg/h for 4 hours; 0.6 mg/kg/h for 4 hours; 0.9 mg/kg/h for 4 hours or 0.6 mg/kg/h for 6 hours. Repeat angiograms were obtained to assess the degree of clot lysis. The primary outcome was complete thrombolysis defined as >95% thrombus volume reduction at the end of the microplasmin infusion. Safety evaluation included bleedings, adverse events and coagulation biomarkers. RESULTS: Complete thrombolysis was obtained in 3 of the 19 treated patients at the end of microplasmin infusion. Thrombus volume reduction between 50% and 95% was achieved with all dosing regimens. Clinically significant distal embolization occurred in 8 patients. One major and two non-major bleedings occurred. Microplasmin depleted α2-anti-plasmin and decreased fibrinogen. CONCLUSION: Intrathrombus infusion of microplasmin for 4 or 6 hours resulted in significant clot lysis. Distal embolization appeared the most important limitation.