Comparison of Standard Versus High Dose Urokinase for Dysfunctional Tunneled Dialysis Catheters in Haemodialysis Patients: a Randomized Controlled Trial (SHUT)

National Healthcare Group, Singapore

Status and phase: Completed; Phase 4

Conditions: Randomised Controlled Trial; Hemodialysis; Dialysis Access Dysfunction; Thrombolytic Therapy; End Stage Renal Disease (ESRD)

Treatments: Drug: Urokinase

Study type: Interventional

Funder types: Other

Identifiers

NCT06802679

Comparison of Standard versus (Other Grant/Funding Number)

AHEG2007

Details and patient eligibility

About

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.

Enrollment: 44 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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44 participants in 2 patient groups, including a placebo group

HIgh dose urokinase

Active Comparator group

Description:

Patients will be assessed for eligibility for study by nephrologist on duty who is also a PI or Co-I. Patients who meet inclusion criteria will be enrolled in study and informed consent taken. A trained HD nurse will test the catheter of the patient presenting with TDC dysfunction. Once TDC dysfunction is confirmed, patients will be randomized to one of 2 groups and urokinase instillation done according to protocol (see section F9) After a minimum dwell time of 2 hours, urokinase is aspirated and catheter tested by a trained HD nurse. Haemodialysis is then carried out via the catheter. Baseline clinical data, urokinase and hemodialysis details will be recorded for each patient visit as per data collection template.

Treatment:

Drug: Urokinase

Drug: Urokinase

Standard dose urokinase

Placebo Comparator group

Description:

same as above but with different dosage of urokinase

Treatment:

Drug: Urokinase

Drug: Urokinase