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Phase II Trial of Alfimeprase, a Novel-Acting Fibrin Degradation Agent, for Occluded Central Venous Access Devices

Stephan Moll, Peter Kenyon, Luigi Bertoli, James De Maio, Howard Homesley, Steven R. Deitcher

From the University of North Carolina School of Medicine, Chapel Hill; Brody School of Medicine at Eastern Carolina University, Greenville, NC; Corvallis Clinic, Corvallis, OR; Clinical Research Consultants, Hoover, AL; Northwest Medical Specialties, Tacoma, WA; The Cleveland Clinic Foundation, Cleveland, OH; and Nuvelo Inc, San Carlos, CA.

Address reprint requests to Steven R. Deitcher, MD, Nuvelo Inc, 201 Industrial Rd, Suite 310, San Carlos, CA 94070; e-mail: sdeitcher{at}nuvelo.com

PURPOSE: Alfimeprase is a recombinantly produced, genetically modified variant of the metalloproteinase, fibrolase. Alfimeprase proteolytically cleaves fibrin, independent of plasminogen activation to plasmin, and directly dissolves thrombi. Based on the direct fibrin degradation effect of alfimeprase, rapid activity in patients with occluded central venous access devices (CVADs) was hypothesized.

PATIENTS AND METHODS: We performed a phase II, randomized, double-blind, active-control, multicenter, dose-ranging study to compare the safety and efficacy of one or two instillations of three intraluminal doses of alfimeprase (0.3, 1.0, and 3.0 mg) and alteplase 2.0 mg in re-establishing patency to occluded CVADs in 55 adult patients.

RESULTS: All three alfimeprase doses were more successful than alteplase during the first 15 and 30 minutes of treatment. The alfimeprase 3.0-mg dose resulted in 40%, 50%, and 60% patency restoration rates at 5, 15, and 30 minutes, respectively, compared with 0%, 0%, and 23% for alteplase. The difference at 15 minutes was highly significant (P = .0075). Alfimeprase 3.0 mg produced the highest patency rate at 120 minutes after the first (60%) and second (80%) doses. No major hemorrhagic or embolic events were reported.

CONCLUSION: A single 1- or 3-mg dose of alfimeprase has the potential to restore function to occluded CVADs rapidly and safely, and to facilitate on-time infusion of vital therapies.

Supported by Nuvelo Inc, San Carlos, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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