Clinical trial NCT05248620: Prophylactic Antibiotic Treatment in Hemodialysis
Official title: Prophylactic Antibiotic Treatment in End Stage Kidney Disease and Central Venous Catheter as Hemodialysis Vascular Access
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hemodialysis
Keywords: Blood stream infections
Severe culture negative infections
Central venous catheter
Prophylactic antibiotics
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
First posted: 2022-02-21
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, randomized, single-blinded, placebo controlled study, with blinded endpoint evaluation
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* End Stage Kidney Disease (ESKD) patients who receive an uncuffed or cuffed CVC for expected chronic HD, regardless of previous ESKD treatment modality (PD or KTX) and hemodialysis access (AV-fistula or AV-graft))
* ≥18 years
* Ability to understand the study background, risk and benefit of treatment and to give written informed consent

Exclusion Criteria:

* Unable to give informed consent
* Known intolerance to beta-lactam antibiotics and clindamycin
* Active infection treated with antibiotics
* Breastfeeding
* Pregnancy. In women of childbearing age, an approved birth control must be ensured at least 1 month before and during all the 6 months of antibiotic/placebo treatment.

Patients may be rescreened later i.e. within a time period of one month from start of HD, if exclusion criteria are reversible.

Primary outcomes:
measure: Number of patients with Blood stream infection (BSI)
timeFrame: ≤ 6 months after randomization
measure: Number of patients with Severe blood culture negative infection
timeFrame: ≤ 6 months after randomization
Secondary outcomes:
measure: Number of patients with BSI or severe blood culture negative infection
timeFrame: ≤ 6 months after randomization
measure: Mortality
timeFrame: ≤ 6 months after randomization
Other outcomes:
measure: Number of patients with Sepsis
timeFrame: ≤ 6 months after randomization
measure: Number of patients with Deep tissue infection
timeFrame: ≤ 6 months after randomization
measure: Number of patients with Autoinfection
timeFrame: ≤ 6 months after randomization
measure: Number of patients with Clostridium difficile infection
timeFrame: ≤ 6 months after randomization
measure: Mortality due to infection - number of patients
timeFrame: ≤ 6 months after randomization
measure: Number of CVC removals
timeFrame: ≤ 6 months after randomization
measure: Use of Antibiotics in Difined Daily Doses
timeFrame: ≤ 6 months after randomization
measure: Healt-care economics
timeFrame: ≤ 6 months after randomization
measure: Number of patients with Extended Spectrum Beta-Lactamase (ESBL) infection
timeFrame: ≤ 6 months after randomization
measure: Number of patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection
timeFrame: ≤ 6 months after randomization
measure: Number of patients with Carbapenemase-Producing Organisms (CPO) infection
timeFrame: ≤ 6 months after randomization
measure: Number of patients with Vancomycin-resistant enterococci (VRE) infection
timeFrame: ≤ 6 months after randomization
measure: Number of patients with Cardiovascular events
timeFrame: ≤ 6 months after randomization
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: Capital Region
city: Copenhagen
country: Denmark
facility: Herlev-Gentofte Hospital
state: Capital Region
city: Hillerød
country: Denmark
facility: North Zealand Hospital Hillerød
state: Capital Region
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
state: Middle Region
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
state: North Region
city: Roskilde
country: Denmark
facility: ZUH Roskilde
state: Region Sjaelland
city: Odense
country: Denmark
facility: Odense University Hospital
state: Region South
Study officials:
affiliation: Dept. cardiology, Zealand University Hospital, Roskilde, Denmark
name: Niels E Bruun, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.