Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to assess the efficacy of prophylactic antibiotic treatment on blood stream infections and severe culture negative infections, in patients on newly started hemodialysis(HD), with a central venous catheter as vascular access.
After being informed about the study and potential risks all eligible patients, giving written informed consent will be included in the study. At week 0 patients will be randomized in a single blinded manner (participants and care providers) in a 1:1 manner to receive 500/125mg amoxicillin/clavulanic acid 30-120 minutes before each hemodialysis with a central venous catheter (CVC) as vascular access, or corresponding placebo. The timing of antibiotic administration has been established in a pilot-study in order to secure a sufficient concentration of antibiotics during the dialysis session. In case of side effects to amoxicillin/clavulanic acid, the prophylactic antibiotic will be shifted to 600mg clindamycin. Total treatment period with prophylactic antibiotics is 6 months, with a 1 year follow-up.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active | Active Comparator | Amoxicillin/clavulanic acid 500/125mg, tablets, will be administered before each hemodialysis for 6 months |
|
| Placebo | Placebo Comparator | Placebo tablets, similar to the active drug, will be administered before each hemodialysis for 6 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amoxicillin Clavulanic 500/125mg or placebo | Drug | Prophylactic antibiotic treatment |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with Blood stream infection (BSI) | Hospitalization for BSI | ≤ 6 months after randomization |
| Number of patients with Severe blood culture negative infection | Hospitalization ≥ 3 days due to infection defined as: C-reactive protein (CRP) ≥ 75 and negative blood cultures, treated with iv antibiotics | ≤ 6 months after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with BSI or severe blood culture negative infection | Each of the components in the primary endpoint | ≤ 6 months after randomization |
| Mortality | All-cause mortality |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with Sepsis | Hospitalization due to sepsis or septic shock | ≤ 6 months after randomization |
| Number of patients with Deep tissue infection | Infective endocarditis, osteomyelitis, and spondylodiscitis |
Inclusion Criteria:
Exclusion Criteria:
Patients may be rescreened later i.e. within a time period of one month from start of HD, if exclusion criteria are reversible.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Niels E Bruun, Professor | Contact | +4525159309 | nbru@regionsjaelland.dk | |
| Kasper K Iversen, Professor | Contact | Kasper.Karmark.Iversen@regionh.dk |
| Name | Affiliation | Role |
|---|---|---|
| Niels E Bruun, Professor | Dept. cardiology, Zealand University Hospital, Roskilde, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet | Not yet recruiting | Copenhagen | Capital Region | 2100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24001331 | Background | Gupta V, Yassin MH. Infection and hemodialysis access: an updated review. Infect Disord Drug Targets. 2013 Jun;13(3):196-205. doi: 10.2174/1871526511313030008. | |
| 25637641 | Background | Vogelzang JL, van Stralen KJ, Noordzij M, Diez JA, Carrero JJ, Couchoud C, Dekker FW, Finne P, Fouque D, Heaf JG, Hoitsma A, Leivestad T, de Meester J, Metcalfe W, Palsson R, Postorino M, Ravani P, Vanholder R, Wallner M, Wanner C, Groothoff JW, Jager KJ. Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry. Nephrol Dial Transplant. 2015 Jun;30(6):1028-37. doi: 10.1093/ndt/gfv007. Epub 2015 Jan 29. |
Not provided
Not provided
No plan
Not provided
Not provided
Not provided
Not provided
Not provided
Multicenter, randomized, single-blinded, placebo controlled study, with blinded endpoint evaluation
Not provided
Not provided
Amoxicillin/placebo is provided in identical containers. Amoxicillin and placebo tablets are looking similar, but by decision of the Danish Medicines Agency amoxicillin tablets must not be removed from the original folio packing prior to use. Clindamycin active and placebo tablets look similar (incapsulated), and are provided in identical containers. Study medicine will be provided by 1-2 nurses at each site, who are unblinded. The patients and care providers are blinded
| ≤ 6 months after randomization |
| ≤ 6 months after randomization |
| Number of patients with Autoinfection | Frequency of BSI autoinfection | ≤ 6 months after randomization |
| Number of patients with Clostridium difficile infection | Clostridium difficile infection - numbers and days of admission | ≤ 6 months after randomization |
| Mortality due to infection - number of patients | Mortality due to infection | ≤ 6 months after randomization |
| Number of CVC removals | CVC removal due to CVC infection | ≤ 6 months after randomization |
| Use of Antibiotics in Difined Daily Doses | Total use of antibiotics in Defined Daily Doses | ≤ 6 months after randomization |
| Healt-care economics | Health-care related economic consequences due to hospitalization and treatment of the disease | ≤ 6 months after randomization |
| Number of patients with Extended Spectrum Beta-Lactamase (ESBL) infection | ESBL infections - number of patients and days of admission | ≤ 6 months after randomization |
| Number of patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection | MRSA infections - number of patients and days of admission | ≤ 6 months after randomization |
| Number of patients with Carbapenemase-Producing Organisms (CPO) infection | CPO infections - number og patients and days of admission | ≤ 6 months after randomization |
| Number of patients with Vancomycin-resistant enterococci (VRE) infection | VRE infections - number of patients and days of admission | ≤ 6 months after randomization |
| Number of patients with Cardiovascular events | Hospitalization with acute myocardial infarction, worsening heart failure or stroke | ≤ 6 months after randomization |
| Herlev-Gentofte Hospital | Recruiting | Copenhagen | Capital Region | 2730 | Denmark |
|
| North Zealand Hospital Hillerød | Not yet recruiting | Hillerød | Capital Region | 3400 | Denmark |
|
| Aarhus University Hospital | Not yet recruiting | Aarhus | Middle Region | 8200 | Denmark |
|
| Aalborg University Hospital | Recruiting | Aalborg | North Region | 9100 | Denmark |
|
| ZUH Roskilde | Recruiting | Roskilde | Region Sjælland | 4000 | Denmark |
|
| Odense University Hospital | Recruiting | Odense | Region South | 5000 | Denmark |
|
| 24854263 | Background | Aslam S, Vaida F, Ritter M, Mehta RL. Systematic review and meta-analysis on management of hemodialysis catheter-related bacteremia. J Am Soc Nephrol. 2014 Dec;25(12):2927-41. doi: 10.1681/ASN.2013091009. Epub 2014 May 22. |
| 11012910 | Background | Sarnak MJ, Jaber BL. Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int. 2000 Oct;58(4):1758-64. doi: 10.1111/j.1523-1755.2000.00337.x. |
| 15882306 | Background | Jaber BL. Bacterial infections in hemodialysis patients: pathogenesis and prevention. Kidney Int. 2005 Jun;67(6):2508-19. doi: 10.1111/j.1523-1755.2005.00364.x. No abstract available. |
| 19861670 | Background | de Jager DJ, Grootendorst DC, Jager KJ, van Dijk PC, Tomas LM, Ansell D, Collart F, Finne P, Heaf JG, De Meester J, Wetzels JF, Rosendaal FR, Dekker FW. Cardiovascular and noncardiovascular mortality among patients starting dialysis. JAMA. 2009 Oct 28;302(16):1782-9. doi: 10.1001/jama.2009.1488. |
| 30176809 | Background | Chaudry MS, Gislason GH, Kamper AL, Rix M, Dahl A, Ostergaard L, Fosbol EL, Lauridsen TK, Oestergaard LB, Hassager C, Torp-Pedersen C, Bruun NE. The impact of hemodialysis on mortality risk and cause of death in Staphylococcus aureus endocarditis. BMC Nephrol. 2018 Sep 3;19(1):216. doi: 10.1186/s12882-018-1016-0. |
| 28974524 | Background | Chaudry MS, Carlson N, Gislason GH, Kamper AL, Rix M, Fowler VG Jr, Torp-Pedersen C, Bruun NE. Risk of Infective Endocarditis in Patients with End Stage Renal Disease. Clin J Am Soc Nephrol. 2017 Nov 7;12(11):1814-1822. doi: 10.2215/CJN.02320317. Epub 2017 Oct 3. |
| 30572826 | Background | Nelveg-Kristensen KE, Laier GH, Heaf JG. Risk of death after first-time blood stream infection in incident dialysis patients with specific consideration on vascular access and comorbidity. BMC Infect Dis. 2018 Dec 20;18(1):688. doi: 10.1186/s12879-018-3594-7. |
| 26959243 | Background | Sakhuja A, Nanchal RS, Gupta S, Amer H, Kumar G, Albright RC, Kashani KB. Trends and Outcomes of Severe Sepsis in Patients on Maintenance Dialysis. Am J Nephrol. 2016;43(2):97-103. doi: 10.1159/000444684. Epub 2016 Mar 10. |