Phase II trial of alfimeprase, a novel-acting fibrin degradation agent, for occluded central venous access devices.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Moll
Stephan
S
University of North Carolina School of Medicine, Chapel Hill, USA.
Kenyon
Peter
P
Bertoli
Luigi
L
De Maio
James
J
Homesley
Howard
H
Deitcher
Steven R
SR
D000328:Adult; D000368:Aged; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000627:therapeutic use*; D008875:Middle Aged; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D008666:Metalloendopeptidases; C436755:alfimeprase