Evaluation of Prophylactic Amoxicillin/Clavulanic Acid or Clindamycin in Preventing Bloodstream Infections in Hemodialysis Patients with Central Venous Catheters

The primary objective of this study is to evaluate the effect of **prophylactic antibiotic treatment** with amoxicillin/clavulanic acid, or clindamycin for those intolerant to beta-lactams, on the incidence of bloodstream infections (BSI) and severe blood culture-negative infections in patients with end-stage kidney disease undergoing hemodialysis (HD) using a central venous catheter (CVC) as vascular access. This is assessed during the first six months following the initiation of hemodialysis. The clinical relevance of this objective lies in potentially reducing infection rates, which are a significant complication in patients with renal failure treated with hemodialysis, thereby improving patient outcomes and reducing healthcare burdens.

Secondary objectives include comparing the bacterial genome from pathogens isolated from blood samples with the genome of pathogens in the patient's own microbiota in HD patients with BSI and CVC as vascular access. This comparison may provide insights into the source and transmission of infections, aiding in the development of targeted prevention strategies.

The clinical trial involves participants diagnosed with **blood poisoning** in patients with renal failure undergoing hemodialysis. The study population includes both male and female subjects, with an age range encompassing adults and the elderly. Participants are in general good health, aside from their primary condition of end-stage kidney disease (ESKD). The trial does not involve a vulnerable population. The total number of participants is not provided by the sponsor. Selection criteria include ESKD patients who have received an uncuffed or cuffed central venous catheter (CVC) for expected chronic hemodialysis, irrespective of previous ESKD treatment modalities such as peritoneal dialysis or kidney transplantation, and prior hemodialysis access methods like arteriovenous fistula or graft. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **placebo-controlled** study to evaluate the effect of prophylactic antibiotic treatment in patients with end-stage kidney disease undergoing hemodialysis. The trial will assess the efficacy of **amoxicillin/clavulanic acid** or **clindamycin** for those intolerant to beta-lactams, administered in relation to the hemodialysis procedure. The primary objective is to determine the impact on bloodstream infections and severe blood culture-negative infections within the first six months of initiating hemodialysis using a central venous catheter as vascular access. The trial is expected to run from September 2020 to December 2027, with participant involvement lasting up to six months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as having end-stage kidney disease and receiving a central venous catheter for chronic hemodialysis. Follow-up visits will occur regularly to monitor the participants' health status, adherence to the medication regimen, and any adverse events. The end-of-study visit will conclude the trial for each participant, assessing the primary and secondary endpoints, including hospitalization due to bloodstream infections or infections requiring intravenous antibiotics. Participants may be withdrawn from the study early if they experience significant adverse effects, non-compliance with the study protocol, or if they choose to withdraw consent.

The clinical trial involves the administration of **Clindamycin** "Alternova", which is provided in the form of hard capsules. The active substance, clindamycin, is of chemical origin and is classified under the ATC code J01FF01. The maximum daily dose for clindamycin is 300 mg, with a total maximum dose of 36 g over the treatment period. The capsules are administered orally, and the treatment duration is set for a maximum of 6 months. Participant compliance with the dosing schedule will be monitored throughout the trial.

Additionally, the trial includes the use of **Amoxicillin**/clavulanic acid "Aurobindo", available as film-coated tablets. The active substances, amoxicillin and clavulanic acid, are also of chemical origin, with the ATC classification J01CR02. The maximum daily dose for this combination is 500 mg, with a total maximum dose of 60 g over the treatment period. These tablets are administered orally, and the treatment duration is similarly set for a maximum of 6 months. Compliance with the dosing regimen will be closely monitored to ensure adherence to the protocol.

Both medications are used as part of a prophylactic antibiotic treatment strategy in patients with end-stage kidney disease undergoing hemodialysis with a central venous catheter. The trial is designed to evaluate the effect of these antibiotics on bloodstream infections and severe blood culture-negative infections during the initial 6 months of hemodialysis. The choice between clindamycin and amoxicillin/clavulanic acid is determined by the patient's tolerance to beta-lactam antibiotics, with clindamycin being used for those who are intolerant.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoints, which include hospitalization for **bloodstream infection (BSI)** within 6 months after randomization and hospitalization for 3 or more days due to infection characterized by C-reactive protein (CRP) levels of 75 or higher, negative blood cultures, and treatment with intravenous antibiotics, occurring within 6 months post-randomization. The trial aims to determine the effect of prophylactic antibiotic treatment with amoxicillin/clavulanic acid, or clindamycin for those intolerant to beta-lactams, administered in relation to the hemodialysis (HD) procedure on BSI and severe blood culture-negative infections during the first 6 months after initiation of hemodialysis with a central venous catheter (CVC) as vascular access. The efficacy parameters will be collected and analyzed over a 6-month period following randomization, with the primary focus on hospitalization events related to infections as defined by the trial's criteria.