Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Improvement of Hemodialysis Catheter Function with Tenecteplase: A Phase III, Open-Label Study: TROPICS 4

Abstract

Hemodialysis (HD) catheters are prone to thrombotic occlusion. We evaluated tenecteplase, a thrombolytic, for the treatment of dysfunctional HD catheters. Patients with tunneled HD catheters and blood flow rate (BFR) <300 mL/min received open-label tenecteplase (2 mg/lumen) for a 1 h intracatheter dwell. Treatment success was defined as BFR ≥300 mL/min and a ≥25 mL/min increase from baseline BFR, 30 min before and at the end of HD. Patients without treatment success at the end of the initial visit received another 2 mg dose of tenecteplase for an up to 72 h extended dwell. Of 223 enrolled patients, 34% (95% confidence interval [CI], 28–40%) had treatment success after a 1 h dwell. Mean (standard deviation [SD]) BFR change from baseline was 82 (124) mL/min. Treatment success in those who received extended-dwell tenecteplase (n = 116) was 49% (95% CI, 40–58%), with mean (SD) BFR change from baseline of 117 (140) mL/min. Reported targeted adverse events included five catheter-related bloodstream infections and one thrombosis. No intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications were reported. Tenecteplase administered as a 1 h or 1 h plus extended dwell was associated with improved HD catheter function in the TROPICS 4 trial.

This is a preview of subscription content, log in to check access.

Fig. 1

References

  1. 1.

    National Kidney Foundation (2006) Clinical practice guidelines for vascular access. Am J Kidney Dis 48(suppl 1):S248–S273

  2. 2.

    US Renal Data System (2009) USRDS 2009 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD

  3. 3.

    Little MA, O’Riordan A, Lucey B, Farrell M, Lee M, Conlon PJ, Walshe JJ (2001) A prospective study of complications associated with cuffed, tunnelled haemodialysis catheters. Nephrol Dial Transplant 16:2194–2200

  4. 4.

    Trerotola SO, Johnson MS, Harris VJ, Shah H, Ambrosius WT, McKusky MA, Kraus MA (1997) Outcome of tunneled hemodialysis catheters placed via the right internal jugular vein by interventional radiologists. Radiology 203:489–495

  5. 5.

    Schwab SJ, Buller GL, McCann RL, Bollinger RR, Stickel DL (1988) Prospective evaluation of a Dacron cuffed hemodialysis catheter for prolonged use. Am J Kidney Dis 11:166–169

  6. 6.

    Suhocki PV, Conlon PJ Jr, Knelson MH, Harland R, Schwab SJ (1996) Silastic cuffed catheters for hemodialysis vascular access: thrombolytic and mechanical correction of malfunction. Am J Kidney Dis 28:379–386

  7. 7.

    Thomas A (2005) Revisiting quality standards in hemodialysis vascular access: where is the bar? Relationship of dose of hemodialysis and cause-specific mortality. CANNT J 15:30–41

  8. 8.

    Bamgbola OF, Del Rio M, Kaskel FJ, Flynn JT (2005) Recombinant tissue plasminogen activator infusion for hemodialysis catheter clearance. Pediatr Nephrol 20:989–993

  9. 9.

    Bour ES, Weaver AS, Yang HC, Gifford RR (1990) Experience with the double lumen Silastic catheter for hemoaccess. Surg Gynecol Obstet 171:33–39

  10. 10.

    Brunner MC, Matalon TA, Patel SK, McDonald V, Jensik SC (1991) Ultrarapid urokinase in hemodialysis access occlusion. J Vasc Interv Radiol 2:503–506

  11. 11.

    Castner D (2001) The efficacy of reteplase in the treatment of thrombosed hemodialysis venous catheters. Nephrol Nurs J 28:403–410

  12. 12.

    Daeihagh P, Jordan J, Chen J, Rocco M (2000) Efficacy of tissue plasminogen activator administration on patency of hemodialysis access catheters. Am J Kidney Dis 36:75–79

  13. 13.

    Davies J, Casey J, Li C, Crowe AV, McClelland P (2004) Restoration of flow following haemodialysis catheter thrombus. Analysis of rt-PA infusion in tunnelled dialysis catheters. J Clin Pharm Ther 29:517–520

  14. 14.

    Dowling K, Sansivero G, Stainken B, Siskin G, Dolen E, Ahn J, Mitchell N (2004) The use of tissue plasminogen activator infusion to re-establish function of tunneled hemodialysis catheters. Nephrol Nurs J 31:199–200

  15. 15.

    Eyrich H, Walton T, Macon EJ, Howe A (2002) Alteplase versus urokinase in restoring blood flow in hemodialysis-catheter thrombosis. Am J Health Syst Pharm 59:1437–1440

  16. 16.

    Falk A, Samson W, Uribarri J, Vassalotti JA (2004) Efficacy of reteplase in poorly functioning hemodialysis catheters. Clin Nephrol 61:47–53

  17. 17.

    Haymond J, Shalansky K, Jastrzebski J (2005) Efficacy of low-dose alteplase for treatment of hemodialysis catheter occlusions. J Vasc Access 6:76–82

  18. 18.

    Hilleman DE, Dunlay RW, Packard KA (2003) Reteplase for dysfunctional hemodialysis catheter clearance. Pharmacotherapy 23:137–141

  19. 19.

    Hyman G, England M, Kibede S, Lee P, Willets G (2004) The efficacy and safety of reteplase for thrombolysis of hemodialysis catheters at a community and academic regional medical center. Nephron Clin Pract 96:c39–c42

  20. 20.

    Jacobs BR, Haygood M, Hingl J (2001) Recombinant tissue plasminogen activator in the treatment of central venous catheter occlusion in children. J Pediatr 139:593–596

  21. 21.

    Little MA, Walshe JJ (2002) A longitudinal study of the repeated use of alteplase as therapy for tunneled hemodialysis catheter dysfunction. Am J Kidney Dis 39:86–91

  22. 22.

    Macrae JM, Loh G, Djurdjev O, Shalansky S, Werb R, Levin A, Kiaii M (2005) Short and long alteplase dwells in dysfunctional hemodialysis catheters. Hemodial Int 9:189–195

  23. 23.

    Meers C, Toffelmire EB (1998) Urokinase efficacy in the restoration of hemodialysis catheter function. J CANNT 8:17–19

  24. 24.

    Meers C, Toffelmire EB (1999) Tissue plasminogen activator (t-PA) efficacy in the restoration of hemodialysis catheter function. CANNT J 9:25–28

  25. 25.

    Moss AH, Vasilakis C, Holley JL, Foulks CJ, Pillai K, McDowell DE (1990) Use of a silicone dual-lumen catheter with a Dacron cuff as a long-term vascular access for hemodialysis patients. Am J Kidney Dis 16:211–215

  26. 26.

    Nguyen TV, Dikun M (2004) Establishing an alteplase dosing protocol for hemodialysis-catheter thrombosis. Am J Health Syst Pharm 61:1922–1924

  27. 27.

    Northsea C (1994) Using urokinase to restore patency in double lumen catheters. ANNA J 21:261–264 273

  28. 28.

    Paulsen D, Reisoether A, Aasen M, Fauchald P (1993) Use of tissue plasminogen activator for reopening of clotted dialysis catheters. Nephron 64:468–470

  29. 29.

    Peska DN, DeLange B, Gratch JO, Bleicher JN, Pertusi RM, Mueller D (1997) Short-term continuous infusion thrombolytic therapy for occluded central nervous venous dialysis catheters. Am J Manag Care 3:261–264

  30. 30.

    Prabhu PN, Kerns SR, Sabatelli FW, Hawkins IF, Ross EA (1997) Long-term performance and complications of the Tesio twin catheter system for hemodialysis access. Am J Kidney Dis 30:213–218

  31. 31.

    Twardowski ZJ (1998) High-dose intradialytic urokinase to restore the patency of permanent central vein hemodialysis catheters. Am J Kidney Dis 31:841–847

  32. 32.

    Zacharias JM, Weatherston CP, Spewak CR, Vercaigne LM (2003) Alteplase versus urokinase for occluded hemodialysis catheters. Ann Pharmacother 37:27–33

  33. 33.

    Keyt BA, Paoni NF, Refino CJ, Berleau L, Nguyen H, Chow A, Lai J, Pena L, Pater C, Ogez J, Etcheverry T, Botstein D, Bennett WF (1994) A faster-acting and more potent form of tissue plasminogen activator. Proc Natl Acad Sci USA 91:3670–3674

  34. 34.

    Refino CJ, Paoni NF, Keyt BA, Pater CS, Badillo JM, Wurm FM, Ogez J, Bennett WF (1993) A variant of t-PA (T103N, KHRR 296–299 AAAA) that, by bolus, has increased potency and decreased systemic activation of plasminogen. Thromb Haemost 70:313–319

  35. 35.

    Tumlin J, Goldman J, Spiegel D, Roer D, Ntoso K, Blaney M, Jacobs J, Gillespie BS, Begelman SM (2010) A phase III, randomized, double-blind, placebo-controlled study of tenecteplase for improvement of hemodialysis catheter function: TROPICS 3. Clin J Am Soc Nephrol 5:631–636

  36. 36.

    Senecal L, Saint-Sauveur E, Leblanc M (2004) Blood flow and recirculation rates in tunneled hemodialysis catheters. Relationship of dose of hemodialysis and cause-specific mortality. ASAIO J 50:94–97

  37. 37.

    Twardowski ZJ, Van Stone JC, Jones ME, Klusmeyer ME, Haynie JD (1993) Blood recirculation in intravenous catheters for hemodialysis. J Am Soc Nephrol 3:1978–1981

  38. 38.

    Saxena AK, Panhotra BR (2005) Haemodialysis catheter-related bloodstream infections: current treatment options and strategies for prevention. Swiss Med Wkly 135:127–138

  39. 39.

    Cannon CP, McCabe CH, Gibson CM, Ghali M, Sequeira RF, McKendall GR, Breed J, Modi NB, Fox NL, Tracy RP, Love TW, Braunwald E (1997) TNK-tissue plasminogen activator in acute myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 10A dose-ranging trial Relationship of dose of hemodialysis and cause-specific mortality. Circulation 95:351–356

  40. 40.

    Cannon CP, Gibson CM, McCabe CH, Adgey AA, Schweiger MJ, Sequeira RF, Grollier G, Giugliano RP, Frey M, Mueller HS, Steingart RM, Weaver WD, Van de Werf F, Braunwald E (1998) TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction: results of the TIMI 10B trial. Thrombolysis in Myocardial Infarction (TIMI) 10B Investigators. Circulation 98:2805–2814

Download references

Acknowledgments

This study was sponsored by Genentech, Inc. Support for third-party medical writing assistance was provided by Genentech, Inc. Steven Fishbane has received research support from Genentech; Samuel Milligan has nothing to declare; Kenneth Lempert has nothing to declare; Joachim Hertel has received research support from Genentech; James Wetmore has nothing to declare; Matthew Oliver has nothing to declare; Martha Blaney is an employee of Genentech and has stock ownership interest in Roche; Barbara Gillespie is employed by Quintiles, Inc, the research organization that was contracted by Genentech to execute the TROPICS trials; Joan Jacobs is an employee of Genentech and has stock ownership interest in Roche; Susan Begelman is an employee of Genentech and has stock ownership interest in Roche.

Author information

Correspondence to Steven Fishbane.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fishbane, S., Milligan, S.L., Lempert, K.D. et al. Improvement of Hemodialysis Catheter Function with Tenecteplase: A Phase III, Open-Label Study: TROPICS 4. J Thromb Thrombolysis 31, 99–106 (2011). https://doi.org/10.1007/s11239-010-0493-1

Download citation

Keywords

  • Chronic renal failure
  • Dialysis catheter
  • End-stage renal disease
  • Hemodialysis
  • Tenecteplase
  • Thrombolytic