Clinical trial NCT06802679: Comparison of Standard Versus High Dose Urokinase for Dysfunctional Tunneled Dialysis Catheters in Haemodialysis Patients: a Randomized Controlled Trial
Official title: Comparison of Standard Versus High Dose Urokinase for Dysfunctional Tunneled Dialysis Catheters in Haemodialysis Patients: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hemodialysis
Thrombolytic Therapy
Dialysis Access Dysfunction
Randomised Controlled Trial
End Stage Renal Disease (ESRD)
Keywords: urokinase
Lead sponsor: National Healthcare Group, Singapore
Sponsor class: OTHER_GOV
First posted: 2025-01-31
Enrollment: 44
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Tunneled dialysis catheters (TDCs) remain a frequent form of vascular access for patients undergoing long-term haemodialysis (HD). In our local setting, thrombolytic therapy with urokinase is used as first line therapy to restore catheter patency in patients who develop TDC dysfunction before considering a TDC exchange which is more invasive, requires hospital admission, and involves a higher cost. There are no published local data on the efficacy of Urokinase, though this is widely used in local practice as first line in the management of TDC dysfunction. Previous studies have also varied in terms of study methodology, dose and administration of urokinase in the form of systemic infusion or catheter lock therapy, with varying success rates of 78-97% (2,4-8). Overall, majority of these studies utilized higher doses of urokinase - some studies reported higher patency rates with high dose systemic infusion (4,5) or higher success rates when a higher dose was compared to a lower dose of urokinase lock (6-8). Bleeding events were very rare even in studies that use much higher doses or systemic infusion of urokinase (2,4-8). Our own preliminary data show lower lower success rates of around 52.5% compared to published reports, the question remains on how we can improve our patency rate and cost-effectiveness in treating TDC dysfunction without an increase in risk of adverse events. Therefore, we aim to answer the question as to whether an increase in dose of urokinase will achieve the above outcomes and result in a reduced need for TDC exchange.


Eligibility criteria: Inclusion Criteria:

All HD patients aged 21 or above with TDC dysfunction and able to provide informed consent and do not meet any exclusion criteria are eligible for enrolment in the study.

Catheters eligible for the study include:

(i) Incident catheters that have never received urokinase; including newly inserted catheters for previously enrolled patients are allowed.

(ii) Prevalent catheters that have not received urokinase for the last 6 months

Exclusion Criteria:

* Patients with TDC non-function, defined as no inflow and outflow from both arterial and venous ports upon catheter testing.
* Patients with contraindications to Urokinase including active internal bleeding; recent cerebrovascular accident (\< 2 months); recent intracranial or intraspinal surgery (\< 2 months); intracranial neoplasm, aneurysm or arteriovenous malformation; recent trauma, including cardiopulmonary resuscitation; recent gastrointestinal bleeding (\<2 months); known bleeding diathesis; severe uncontrolled hypertension; known hypersensitivity to Urokinase or any ingredient present in its formulation.
* Pregnancy.
* Tunneled dialysis catheter-related blood stream infection

Primary outcomes:
measure: Primary catheter patency, TDC exchange rate for all visits
timeFrame: 6 months
Secondary outcomes:
measure: Secondary catheter patency, adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Khoo Teck Puat Hospital
Study officials:
References:
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citation: Li Cavoli G, Schillaci O, Zagarrigo C, Servillo F, Li Cavoli TV, Palmeri M, Rotolo U. The urokinase lock-therapy for hemodialysis occluded central venous catheters. Blood Purif. 2015;39(1-3):238. doi: 10.1159/000381007. No abstract available.
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citation: Twardowski ZJ. High-dose intradialytic urokinase to restore the patency of permanent central vein hemodialysis catheters. Am J Kidney Dis. 1998 May;31(5):841-7. doi: 10.1016/s0272-6386(98)70054-x.
citation: Clase CM, Crowther MA, Ingram AJ, Cina CS. Thrombolysis for restoration of patency to haemodialysis central venous catheters: a systematic review. J Thromb Thrombolysis. 2001 Apr;11(2):127-36. doi: 10.1023/a:1011272632286.
citation: Mokrzycki MH, Lok CE. Traditional and non-traditional strategies to optimize catheter function: go with more flow. Kidney Int. 2010 Dec;78(12):1218-31. doi: 10.1038/ki.2010.332. Epub 2010 Sep 29.
citation: Mendes ML, Barretti P, da Silva TN, Ponce D. Approach to thrombotic occlusion related to long-term catheters of hemodialysis patients: a narrative review. J Bras Nefrol. 2015 Apr-Jun;37(2):221-7. doi: 10.5935/0101-2800.20150035. English, Portuguese.