Recombinant urokinase for restoration of patency in occluded central venous access devices

William D. Haire; Steven R. Deitcher; Kathleen M. Mullane; Michael R. Jaff; Carolyn M. Firszt; Gregory A. Schulz; Debra M. Schuerr; Lewis B. Schwartz; Tamyra L. Mouginis; R. Phillip Barton

doi:10.1160/TH03-11-0686

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2004; 92(03): 575-582
DOI: 10.1160/TH03-11-0686

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Recombinant urokinase for restoration of patency in occluded central venous access devices

A double-blind, placebo-controlled trial

Autor*innen

William D. Haire

¹University of Nebraska Medical Center, Omaha, Nebraska, USA
Steven R. Deitcher

²Cleveland Clinic Foundation, Cleveland, Ohio, USA
Kathleen M. Mullane

³Loyola University Medical Center, Maywood, Illinois, USA
Michael R. Jaff

⁴Lenox Hill Hospital, New York, New York, USA
Carolyn M. Firszt

⁵Abbott Laboratories, Abbott Park, Illinois, USA
Gregory A. Schulz

⁵Abbott Laboratories, Abbott Park, Illinois, USA
Debra M. Schuerr

⁵Abbott Laboratories, Abbott Park, Illinois, USA
Lewis B. Schwartz

⁵Abbott Laboratories, Abbott Park, Illinois, USA
Tamyra L. Mouginis

⁵Abbott Laboratories, Abbott Park, Illinois, USA
R. Phillip Barton

⁶Children’s Hospital at Saint Francis,Tulsa, Oklahoma, USA

Abstract

Summary

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 ≤18 years of age. CVAD types included totally implanted subcutaneous ports (45%), PICC lines (26%), non-tunneled percutaneous catheters (18%), and tunneled percutaneous catheters (10%). All CVADs were occluded by virtue of their inability to withdraw blood (withdrawal occlusion). Additionally, 32% of catheters were completely dysfunctional as blood could not be withdrawn and fluids could not be infused (total occlusion). Analysis of the results showed that r-UK was significantly better than placebo in restoring catheter function (54% versus 30%, p = 0.002). There were no major hemorrhagic events within 72 hr after up to four r-UK instillations, and the incidence of non-hemorrhagic events was similar among the r-UK and placebo groups. In conclusion, r-UK is superior to placebo in restoring total catheter patency to occluded CVADs. In patients with occluded CVADs, intra-catheter thrombolysis can restore patency and may obviate the need for catheter replacement.

Keywords

Urokinase - central venous catheter - thrombolysis

Volltext

Referenzen

References
1 Maki DG, Stolz SM, Wheeler S. et al. Prevention of central venous catheter-related bloodstream infection by use of an antisepticimpregnated catheter. Ann Int Med 1997; 127: 257-66.
2 Jacobs BR, Haygood M, Hingl J. Recombinant tissue plasminogen activator in the treatment of central venous catheter occlusion in children. J Pediatr 2001; 139: 593-6.
3 Credo RB, Burke SE, Barker WM. et al. Recombinant urokinase (r-UK): Biochemistry, pharmacology, and clinical experience. New Ther Agents in Thromb & Thrombol 1997; 513-37.
4 Graafsma YP, Prins MH, Lensing WA. et al. Bleeding classification in clinical trials: observer variability and clinical relevance. Thromb Haemost 1997; 78: 1189-92.
5 Ouriel K, Veith FJ, Sasahara AA. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. New Engl J Med 1998; 338: 1105-11.
6 Daeihagh P, Jordan J, Chem J. et al. Efficacy of tissue plasminogen activator administration on patency of hemodialysis access catheters. Am J Kidney Dis 2000; 36: 75-9.
7 Haire WD, Atkinson JB, Stephens LC. et al. Urokinase versus recombinant tissue plasminogen activator in thrombosed central venous catheters: a double-blind randomized trial. Thromb Haemost 1994; 72: 543-7.
8 Suhocki PV, Conion PJ, Knelson MH. et al. Silastic cuffed catheters for hemodialysis vascular access: thrombolytic and mechanical correction of malfunction. Am J Kidney Dis 1996; 28: 379-86.
9 Schwab SJ, Buller GL, McCann RL. et al. Prospective evaluation of a Dacron cuffed hemodialysis catheter for prolonged use. Am J Kidney Dis 1988; 11: 166-9.
10 Deitcher SR, Fesen MR, Kiproff PM. et al. Safety and efficacy of alteplase for restoring function in occluded central venous catheters: Results of the Cardiovascular Thrombolytic to Open Occluded Lines Trial. J Clin Onc 2002; 20: 317-24.
11 Clase CM, Crowther MA, Ingram AJ. et al. Thrombolysis for restoration of patency to hemodialysis central venous catheters: A systematic review. J Throm Thrombolysis 2001; 11: 127-36.
12 Hurtubise MR, Bottino JC, Lawson M. et al. Restoring patency of occluded central venous catheters. Arch Surg 1980; 115: 212-13.
13 Glynn MF, Langer B, Jeejeebhoy KN. Therapy for thrombotic occlusion of longterm intravenous alimentation catheters. J Parenter Enteral Nutr 1980; 04: 387-90.
14 Lawson M, Bottino JC, Hurtubise MR. et al. The use of urokinase to restore the patency of occluded central venous catheters. Am J Intraven Ther Clin Nutr 1982; 09: 29-32.
15 Wachs T. Urokinase administration in pediatric patients with occluded central venous catheters. J Intraven Nurs 1980; 13: 100-2.
16 Northsea C. Using urokinase to restore patency in double lumen catheters. ANNA J 1994; 21: 261-4.
17 Moss AH, Vasilakis C, Holley JL. et al. Use of a silicone dual-lumen catheter with a Dacron cuff as a long-term vascular access for hemodialysis patients. Am J Kidney Dis 1990; 16: 211-5.
18 Bour ES, Weaver AS, Yang HC. et al. Experience with the double lumen Silastic catheter for hemoaccess. Surg Gynecol Obstet 1990; 171: 33-9.
19 Ponec D, Irwin D, Haire WD. et al. Recombinant tissue plasminogen activator (Alteplase) for restoration of flow in occluded central venous access devices: A double-blind placebo-controlled trial The Cardiovascular Thrombolytic to Open Occluded Lines (COOL) efficacy trial. J Vasc Interv Radiol 2001; 12: 951-5.
20 Stephens LC, Haire WD, Kotulak GD. Are clinical signs accurate indicators of the cause of central venous catheter occlusion?. JPEN J Parenter Enteral Nutr 1995; 19: 75-9.