HemodialysisPhase 4SHUTNCT06802679
Comparison of Standard Versus High Dose Urokinase for Dysfunctional Tunneled Dialysis Catheters in Haemodialysis Patients: A Randomized Controlled Trial
A Phase 4 study testing Urokinase in people with Hemodialysis and Thrombolytic Therapy, run by National Healthcare Group, Singapore at 1 site in Singapore.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Hemodialysis, Thrombolytic Therapy, Dialysis Access Dysfunction
- What is being tested?
- Urokinase
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteSingapore
- Study dates
- 1 Oct 2020to 27 Jan 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Incident catheters that have never received urokinase; including newly inserted catheters for previously enrolled patients are allowed.
- Prevalent catheters that have not received urokinase for the last 6 months
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Hemodialysis, Thrombolytic Therapy, Dialysis Access Dysfunction, Randomised Controlled Trial, End Stage Renal Disease (ESRD)
- Being tested
- Urokinase
- Keywords
- urokinase
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UrokinaseDrug
Also called High dose urokinase
In the higher dose group: 30,000unit (1.5ml) per catheter lumen is instilled per catheter lumen (in both arterial and venous ports respectively). This allows utilization of the entire vial of Urokinase to prevent wastage and to assess if this increase in dose improves catheter patency and survival, thus reducing the need for a TDC exchange in our HD patients. The urokinase lock is dwelled for at least 2 hours, after which aspiration and catheter testing will be done by a trained HD nurse.
UrokinaseDrug
Also called Standard dose urokinase
20,000unit (1ml) is instilled per catheter lumen (in both arterial and venous ports respectively); and the remaining 1ml is discarded.
| Study group | Role | What they receive |
|---|---|---|
| HIgh dose urokinase | Active comparator | 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. Receives: Drug: Urokinase |
| Standard dose urokinase | Placebo comparator | same as above but with different dosage of urokinase Receives: Drug: Urokinase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary catheter patency, TDC exchange rate for all visits
Catheter patency right after urokinase aspiration as tested by trained HD nurse (complete / partial / failed) for each patient visit.
Primary patency: Interval between primary intervention (high versus standard dose urokinase) and repeated intervention for recurring dysfunction in a catheter
Measured: 6 months
Secondary outcomes (1)
Secondary catheter patency, adverse events
Secondary patency: Interval between second episode of dysfunction until TDC exchange / removal or other censorship event achieved (death, change of modality)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2025
- Study start1 Oct 2020
- Primary completion4 Jan 2025
- Study completion27 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HemodialysisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Healthcare Group, Singapore
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Allen Liu Yan Lun, National Healthcare Group, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06802679
- Sponsor's protocol ID
- AHEG2007
- Other IDs
- Comparison of Standard versus
- Acronym
- SHUT
- Status last verified
- Jan 2025
- First submitted
- 26 Jan 2025
- Last updated
- 31 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Chang DH, Mammadov K, Hickethier T, Borggrefe J, Hellmich M, Maintz D, Kabbasch C. Fibrin sheaths in central venous port catheters: treatment with low-dose, single injection of urokinase on an outpatient basis. Ther Clin Risk Manag. 2017 Jan 24;13:111-115. doi: 10.2147/TCRM.S125130. eCollection 2017.
PubMed 28182117Li 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.
PubMed 25823425Donati G, Coli L, Cianciolo G, La Manna G, Cuna V, Montanari M, Gozzetti F, Stefoni S. Thrombosis of tunneled-cuffed hemodialysis catheters: treatment with high-dose urokinase lock therapy. Artif Organs. 2012 Jan;36(1):21-8. doi: 10.1111/j.1525-1594.2011.01290.x. Epub 2011 Aug 16.
PubMed 21848863Shavit L, Lifschitz M, Plaksin J, Grenader T, Slotki I. High dose urokinase for restoration of patency of occluded permanent central venous catheters in hemodialysis patients. Clin Nephrol. 2010 Oct;74(4):297-302. doi: 10.5414/cnp74297.
PubMed 20875382Twardowski 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.
PubMed 9590195Clase 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.
PubMed 11406727Mokrzycki 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.
PubMed 20881943Mendes 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.
PubMed 26154643
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Standard Versus High Dose Urokinase for Dysfunctional Tunneled Dialysis Catheters in Haemodialysis Patients: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06802679
- Acronym / sponsor ID
- SHUT / AHEG2007
- Conditions
- Hemodialysis, Thrombolytic Therapy, Dialysis Access Dysfunction, Randomised Controlled Trial, End Stage Renal Disease (ESRD)
- Keywords
- urokinase
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Healthcare Group, SingaporeOther government
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 4 Jan 2025 (actual)
- Study completion
- 27 Jan 2025 (actual)
- First posted
- 31 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIgh dose urokinase | Active comparator | Drug: UrokinasePatients 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. |
| Standard dose urokinase | Placebo comparator | Drug: Urokinasesame as above but with different dosage of urokinase |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
- Incident catheters that have never received urokinase; including newly inserted catheters for previously enrolled patients are allowed.
- Prevalent catheters that have not received urokinase for the last 6 months
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UrokinaseAlso: High dose urokinaseIn the higher dose group: 30,000unit (1.5ml) per catheter lumen is instilled per catheter lumen (in both arterial and venous ports respectively). This allows utilization of the entire vial of Urokinase to prevent wastage and to assess if this increase in dose improves catheter patency and survival, thus reducing the need for a TDC exchange in our HD patients. The urokinase lock is dwelled for at least 2 hours, after which aspiration and catheter testing will be done by a trained HD nurse. | Drug | HIgh dose urokinase |
| UrokinaseAlso: Standard dose urokinase20,000unit (1ml) is instilled per catheter lumen (in both arterial and venous ports respectively); and the remaining 1ml is discarded. | Drug | Standard dose urokinase |
Primary outcome
Primary catheter patency, TDC exchange rate for all visits
Time frame: 6 months
Catheter patency right after urokinase aspiration as tested by trained HD nurse (complete / partial / failed) for each patient visit. Primary patency: Interval between primary intervention (high versus standard dose urokinase) and repeated intervention for recurring dysfunction in a catheter
1 secondary outcome
Secondary catheter patency, adverse events
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2025.
- Results publication: PubMed 28182117Chang DH, Mammadov K, Hickethier T, Borggrefe J, Hellmich M, Maintz D, Kabbasch C. Fibrin sheaths in central venous port catheters: treatment with low-dose, single injection of urokinase on an outpatient basis. Ther Clin Risk Manag. 2017 Jan 24;13:111-115. doi: 10.2147/TCRM.S125130. eCollection 2017.
- Results publication: PubMed 25823425Li 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.
- Results publication: PubMed 21848863Donati G, Coli L, Cianciolo G, La Manna G, Cuna V, Montanari M, Gozzetti F, Stefoni S. Thrombosis of tunneled-cuffed hemodialysis catheters: treatment with high-dose urokinase lock therapy. Artif Organs. 2012 Jan;36(1):21-8. doi: 10.1111/j.1525-1594.2011.01290.x. Epub 2011 Aug 16.
- Results publication: PubMed 20875382Shavit L, Lifschitz M, Plaksin J, Grenader T, Slotki I. High dose urokinase for restoration of patency of occluded permanent central venous catheters in hemodialysis patients. Clin Nephrol. 2010 Oct;74(4):297-302. doi: 10.5414/cnp74297.
- Results publication: PubMed 9590195Twardowski 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.
- Results publication: PubMed 11406727Clase 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.
- Results publication: PubMed 20881943Mokrzycki 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.
- Results publication: PubMed 26154643Mendes 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Urokinase in people with Hemodialysis and Thrombolytic Therapy, run by National Healthcare Group, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary catheter patency, TDC exchange rate for all visits (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06802679, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2025.