Dose-ranging trial with a recombinant urokinase (urokinase alfa) for occluded central venous catheters in oncology patients.
OBJECTIVE
Recombinant urokinase (r-UK) is a high-molecular-weight urokinase produced in transfected, non-human, mammalian cells. A Phase II, randomized, double-blind, parallel, placebo-controlled, dose-ranging study was performed to compare the safety and efficacy of one or two instillations of three intraluminal concentrations of r-UK (5,000; 15,000; and 25,000 IU/mL) with a placebo for reestablishment of total function to occluded central venous access devices (CVADs).


METHODS
One-hundred eight patients with CVAD withdrawal or total occlusion were enrolled and randomized to treatment; 104 patients received at least one instillation of study drug and 101 patients completed treatment. All but one patient had cancer.


RESULTS
All three concentrations of r-UK were significantly superior to placebo in restoring total CVAD function (patency of all occluded lumens) after one or two instillations of study medication (25,000 IU/mL r-UK, 68% vs. placebo, 28% [P =.007]; 15,000 IU/mL r-UK, 69% vs. placebo, 24% [P =.004]; 5,000 IU/mL r-UK, 70% vs. placebo, 28% [P =.003]). Comparisons of the three r-UK concentrations indicated no difference after one or two instillations with regards to patency restoration. Treatment-emergent hemorrhagic events occurring within 72 hours after study drug exposure were experienced by four patients (17%) in the 25,000 IU/mL r-UK group, two patients (7%) in the 15,000 IU/mL r-UK group, no patients in the 5,000 IU/mL r-UK group, and no patients in the placebo group.


CONCLUSIONS
Efficacy and safety results of this study support further evaluation of a 5,000 IU/mL concentration of r-UK for treatment of occluded CVADs in adult and pediatric patients from 1 year of age.
Deitcher
Steven R
SR
Section of Hematology and Coagulation Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio, USA. sdeitcher@nuvelo.com
Fraschini
Giuseppe
G
Himmelfarb
Jonathan
J
Schuman
Earl
E
Smith
Thomas J
TJ
Schulz
Gregory A
GA
Firszt
Carolyn M
CM
Mouginis
Tamyra L
TL
D000293:Adolescent; D000328:Adult; D002405:Catheterization, Central Venous; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006083:Graft Occlusion, Vascular / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007322:Instillation, Drug; D008297:Male; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage*; D014654:Vascular Patency / Q000187:drug effects
D011994:Recombinant Proteins; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator