Prophylactic Antibiotic Treatment in Hemodialysis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prophylactic Antibiotic Treatment in End Stage Kidney Disease and Central Venous Catheter as Hemodialysis Vascular Access

Conditions
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Hemodialysis

Intervention / Treatment
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* Drug: Amoxicillin Clavulanic 500/125mg or placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, randomized, single-blinded, placebo controlled study, with blinded endpoint evaluation
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active<br>Amoxicillin/clavulanic acid 500/125mg, tablets, will be administered before each hemodialysis for 6 months | Drug: Amoxicillin Clavulanic 500/125mg or placebo<br>* Prophylactic antibiotic treatment<br>* Other names: Aurobindo;|
| Placebo Comparator: Placebo<br>Placebo tablets, similar to the active drug, will be administered before each hemodialysis for 6 months | Drug: Amoxicillin Clavulanic 500/125mg or placebo<br>* Prophylactic antibiotic treatment<br>* Other names: Aurobindo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | ≤ 6 months after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood stream infections, Severe culture negative infections, Central venous catheter, Prophylactic antibiotics