A PROSPECTIVE, RANDOMIZED, MULTICENTER TRIAL TO COMPARE A TAUROLOCK™ BASED LOCK SOLUTION TO A CITRATE AND CITRATE/UROKINASE BASED LOCK SOLUTION IN TUNNELED HEMODIALYSIS CATHETERS FOR THE PREVENTION OF BACTEREMIA AND DYSFUNCTION
Patients with end-stage renal disease (ESRD) treated with dialysis often require a well-functioning central venous catheter (CVC) for effective hemodialysis (HD) treatment. Despite great advances in CVC technique, catheter dysfunction (CD) and catheter-related bloodstream-infections (CRBSI) remain a main cause of mortality and morbidity in these patients. Multiple studies have assessed the role of catheter lock solution (CLS) for the prevention of CD and CRBSI.
Heparin is no longer the gold standard for catheter lock, but the question for the best CLS is still not answered. To this time CLS containing citrate, taurolidine and urokinase – alone or in combination – are widely used in dialysis patients with tunneled CVCs. A recent study comparing a Citrate-based CLS with a Taurolidine/Urokinase-based CLS showed a significant reduction in CD and CRBSI in the Taurolidine/Urokinase group. However, the study had several limitations including an unacceptable rate of CRBSI in the control group. Furthermore, it remains unclear whether the positive effects in the Taurolidine/Urokinase-based CLS are mainly driven by Taurolidine or Urokinase.
Rationale for the study
Recent data have shown a possible superiority of Taurolidine-based CLS in tunneled CVCs, regarding CRBSIs and catheter dysfunctions (CD) compared to Citrate-based CLS. Furthermore Taurolidine-based CLS seem to be more cost efficient. However, these publications face relevant limitations, including an unacceptable rate of CRBSI in the control group. Another study has shown that the combination of Taurolidine and Urokinase lowers the combined endpoint of all-causes catheter exchange (CRT and CRBSI) compared to Taurolidine and Heparin. To our knowledge there is no study comparing the combination of Citrate with Urokinase and a Taurolidine-based CLS to this date. Furthermore, the cost efficiency of a Taurolidine-based CLS remains questionable in the case of non-inferiority of a Citrate-Urokinase CLS.
Aims of the study
Aim of this study is to evaluate if a CLS regime of citrate and a CLS regime of citrate combined with Urokinase is non-inferior regarding catheter-related bloodstream infections and catheter dysfunctions compared to Taurolidine-based CLS combined with Heparin and Urokinase.
Partially blinded prospective multicenter randomized controlled trial. Patients will be recruited for this study at the University Hospital of St. Pölten, and State Hospitals in Lower Austria capable of hemodialysis (LK Amstetten, LK Horn, LK Mistelbach, LK Wr. Neustadt).
Ziel: The objective of this study is to evaluate, if a catheter lock solution regime of Sodium Citrate combined with Urokinase and a Taurolidine based catheter lock solution are both better than a Citrate-only based catheter lock solution regarding catheter-related bloodstream infections.
Total number of Catheter Related Blood Stream Infections (CRBSI)
Number of Catheter Dysfunctions (CD)
Rate of catheter removal or exchange due to dysfunctions
Rate of necessity of catheter rescue with Alteplase
Rate of infections per 1000 catheter days
Rate of catheter exchange due to infections
Survival without any CRBSI
Hospitalization (number and days of hospitalization)
Cost analysis (incl. medication, hospitalization)
Use of antibiotics (number of episodes and days)
After written informed consent, patients will be randomized either to the Citrate lock solution group (CiCLS), the Citrate/Urokinase lock solution group (CiUCLS) or the Taurolidine lock solution group (TCLS).
Towards randomization a tunneled dialysis catheter will be inserted in the upper central venous system. Patients will be in a standard dialysis regimen with 3 treatments per week. The first week, respectively the first 3 dialysis sessions, will form a run-in period. Patients with an early CVC dysfunction during the run-in period will be excluded from the study, in order to prevent a possible bias due to mechanical issues of the CVC. After the first dialysis treatment, the CVC will be locked according to the assigned study group.
Subject follow up
Patients will be visited during every dialysis session by the intending physician. Catheter maintenance, diagnosis and treatment of CRBSI and CD will be performed according to defined standard operating procedures. Routine blood sampling will be performed once a month according to our standard of care for dialysis patients. Follow up visits for study purposes will be done every 12 months. All primary and secondary endpoints and all parameters will be recorded in CRFs.
January 2019 - Project plan and study design - done
April 2019 - Submit study to ethical review board - done
September 2019 - Final preparations
October/November 2019 - Start of recruitment
October 2021 - Ende of recruitment
November 2021 - statistical analysis and writing process
Auswirkungen: Individual benefit for patients
CRBSI-free subjects participating in the present study will not have any direct personal benefit from the study. However, they will help to find out which lock solution may the best for preventing CRBSI and CD.
Overall benefit for patients
Multiple studies have assessed and demonstrated the effectiveness of CLS in preventing CRBSIs and CDs in dialysis patients. However, it is unknown which CLS the best is in preventing this remaining causes of mortality and morbidity in dialysis patients with a CVC. Thus, present findings will help to assess whether a combination of 4% Citrate and Urokinase is superior in preventing CRBSIs and CDs compared to a Taurolidine-based regime.
Benefits for the Department and University Hospital
The study will help us to determine the rate of CRBSI und CD in our dialysis patients. Furthermore, the study will help us to find new strategies for prevention and treatment of CRBSIs and CDs. Both are common complications in dialysis patients and are leading to higher mortality and morbidity in this patient group. In addition CRBSIs and CD come along with a higher rate of hospitalization and higher therapy costs.
The use of Taurolock-based lock solution regimens is much more expensive compared to a Citrate-based lock solution regimen. Nevertheless, it remains unclear whether Taurolock is superior in preventing CRBSIs in the presence of stringent hygiene protocols for preventing CRBSIs. This study aims to answer this question.