Safety and Efficacy of Alfimeprase for Restoring Function in Occluded Central Venous Catheters: Interim Results of a Phase 2, Multicenter, Randomized, Double-Blind Study (NuCath).

Abstract

Alfimeprase, a recombinantly produced 22.6 kilodalton metalloproteinase, is a genetically modified variant of fibrolase. Alfimeprase, like fibrolase, proteolytically cleaves both the alpha and beta chains of fibrin(ogen) independent of plasminogen activation to plasmin and directly dissolves thrombi. Readily abundant alpha-2 macroglobulin acts as an endogenous circulating alfimeprase inactivator, forming a covalent, irreversible bond with alfimeprase which results in an inactive complex. Based on the direct thrombolytic effect of alfimeprase, rapid activity was hypothesized. We performed a Phase 2, randomized, double-blind, controlled, dose-ranging study to compare the safety and efficacy of one or two instillations of three intraluminal doses of alfimeprase (0.3 mg; 1.0 mg; and 3.0 mg) and Cathflo® Activase® (Genentech) 2.0 mg in reestablishing patency to occluded central venous access devices (CVADs). This report describes an interim analysis of 48 patients with CVAD withdrawal occlusion who were enrolled and randomized to treatment. Catheter patency was assessed at 5, 15, 30, and 120 minutes after each dose of study drug. Adverse events including bleeding events were assessed for a 30-day period after exposure to study drug. Cumulative patency rates are shown in the table. All study arms had similar patency rates at 120 minutes after the first dose. The alfimeprase 3.0 mg dose produced the highest patency rate at 120 minutes after the second dose. All three alfimeprase doses were more effective than Cathflo® Activase® during the first 30 minutes of treatment. The alfimeprase 1.0 mg and 3.0 mg doses resulted in ≥ 50% patency restoration rates at 15 minutes compared to 0% for Cathflo® Activase®. No intracranial hemorrhage, major hemorrhagic, or embolic events were reported in any treated patients at 5 days. Efficacy and safety results of this study support further evaluation of alfimeprase doses ranging from 1.0 mg to 3.0 mg for treatment of occluded CVADs.Cumulative Patency Rate (%)Alfimeprase 0.3Alfimeprase 1Alfimeprase 3Cathflo ActivaseN=13N=14N=9N=12Baseline0000D 1; 5 min1514440D 1; 15 min1550570D 1; 30 min30505725D 1; 120 min46505750D 2; 5 min46505758D 2; 15 min46505767D 2; 30 min46505767D 2; 120 min46507867D=dose; min=minutes after dose