Recombinant urokinase is safe and effective in restoring patency to occluded central venous access devices: a multiple-center, international trial.

BACKGROUND: The treatment of choice for central venous access device (CVAD) occlusion is intracatheter thrombolysis, which has been reported to reestablish patency in up to 80% of cases. However, these salient results have only been achieved in highly selected CVAD subgroups such as nontunneled devices in adult patients, devices with recent occlusion, and in partially occluded devices through which fluid can still be infused (withdrawal occlusions). Less is known about the success of intracatheter thrombolysis in the broader range of CVAD malfunction encountered in clinical practice, especially in those devices that are totally occluded. OBJECTIVE: This multiple-center, open-label study was performed to test the hypothesis that a new recombinant urokinase (r-UK, urokinase alfa) is safe and effective in reestablishing patency in a large unselected cohort of occluded CVADs. METHODS: Pediatric and adult patients with any type of CVAD occlusion of any duration were treated with 5000 IU/mL intracatheter r-UK. Lumen patency was assessed after 5, 15, and 30 mins; a second dose of r-UK was instilled if the catheter remained occluded after 30 mins. RESULTS: A total of 903 r-UK instillations were performed in 878 patients (age range, 16 days to 96 yrs). Overall, instillation of r-UK successfully restored total catheter patency (all treated lumens) to 75% of CVADs (681 of 902). Patency was restored to at least one occluded lumen in 79% of devices (712 of 902). Patency was restored equally in catheters with total occlusion (76%) as in catheters with only withdrawal occlusion (75%). The median +/- sd time to patency was 15 +/- 20.8 mins (range, 5-203 mins). CONCLUSION: The use of a new r-UK, 5000 IU/mL, is safe and effective for the restoration of patency to occluded CVADs.

Recombinant urokinase for restoration of patency in occluded central venous access devices. A double-blind, placebo-controlled trial.

The interval occlusion of central venous access devices (CVADs) remains a significant clinical problem, often requiring re-intervention for catheter exchange or replacement. The purpose of this Phase 3, multi-center, double-blinded study was to test the hypothesis that instillation of recombinant urokinase (r-UK) 5000 IU/ml is superior to placebo in restoring total catheter patency to an unselected cohort of occluded CVADs. After obtaining informed consent, adult and pediatric patients with occluded, non-hemodialysis CVADs of any duration or type were randomized (2 : 1) to receive either r-UK 5000 IU/ml or placebo instilled into all occluded lumens of their catheter. Catheter function was assessed at 5, 15 and 30 min after the first instillation. If the catheter remained occluded after 30 min, a second dose was instilled with repeat assessments at 5, 15 and 30 min. The primary efficacy variable was the restoration of catheter function to all treated lumens (i.e., total catheter patency) after one or two instillations. Catheters that were not successfully recanalized after two instillations were allowed to receive up to two instillations of open-label r-UK administered in the same manner. The primary safety variable was the occurrence of hemorrhagic and non-hemorrhagic events within 72 hr after instillation. A total of 180 patients were enrolled at 43 sites in the United States and Canada. Most patients were adults, although 20% were

Dose-ranging trial with a recombinant urokinase (urokinase alfa) for occluded central venous catheters in oncology patients.

PURPOSE: 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). MATERIALS AND 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.