Randomized Controlled Trial Comparing Benzylpenicillin Sodium and Cloxacillin in Patients with Penicillin-Susceptible Staphylococcus aureus Bacteremia

The primary objective of this study is to compare the **clinical outcome** in patients with penicillin susceptible **Staphylococcus aureus bacteraemia** treated with bensylpenicillin versus cloxacillin. This comparison is clinically relevant as it aims to determine the most effective antibiotic treatment for this condition, potentially influencing treatment guidelines and improving patient outcomes.

Secondary objectives include evaluating:

• Differences in relapse rate up to 90 days after treatment cessation when treated with bensylpenicillin versus cloxacillin.
• Differences in 90-day mortality between the two treatments.
• Differences in the duration of bacterial DNA presence in the bloodstream when treated with bensylpenicillin versus cloxacillin.
• Frequency of side effects and adverse events in patients with PSSA when treated with cloxacillin compared to bensylpenicillin.
• Differences in the length of intravenous antibiotic treatment between bensylpenicillin and cloxacillin.

The clinical trial focuses on patients diagnosed with **Staphylococcus aureus bacteraemia**, specifically those with penicillin-susceptible strains. The study population includes both male and female participants aged 18 years and older. The trial does not specify the total number of participants, as the sponsor has not provided this information. Participants were selected based on their ability to provide informed consent and their diagnosis of penicillin-susceptible S. aureus bacteraemia. The trial includes a vulnerable population, although specific lifestyle considerations such as diet, physical activity, or habits are not detailed. The selection criteria emphasize the inclusion of adults capable of consenting to participation, ensuring that the study population is appropriately informed and representative of the condition under investigation.

The clinical trial is designed to evaluate the **clinical outcome** in patients with penicillin-susceptible **Staphylococcus aureus bacteraemia** treated with either **benzylpenicillin sodium** or **cloxacillin**. This study is structured as a randomized, controlled trial, with an estimated recruitment start date of February 1, 2024, and an anticipated end date of February 1, 2028. The trial will involve a double-blind methodology to ensure unbiased results. Participants will be randomly assigned to receive either Bensylpenicillin Meda or Cloxacillin Navamedic, both administered intravenously as a solution for injection/infusion. The maximum treatment period for each participant is seven days, with a maximum daily dose of 12 grams and a total dose not exceeding 600 grams.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as being over 18 years of age and having the ability to provide informed consent. Following the initial visit, participants will undergo regular follow-up visits to monitor their response to treatment and any adverse events. The primary endpoint is defined as being alive at day 90 without complications, which include relapse within 90 days from finishing antibiotic treatment or the need for a change or addition of antibiotic treatment due to adverse events or clinical failure. The end-of-study visit will occur at the conclusion of the 90-day follow-up period.

Participant involvement is expected to last approximately 90 days from the start of treatment. Conditions that may lead to early termination from the study include the occurrence of severe adverse events, withdrawal of consent, or any situation where continued participation is deemed not in the best interest of the participant. The trial aims to provide valuable insights into the comparative effectiveness of these two antibiotic treatments in managing Staphylococcus aureus bacteraemia.

The clinical trial involves the administration of **Bensylpenicillin Meda**, a pharmaceutical product formulated as a **solution for injection/infusion**. The active substance in this medication is **benzylpenicillin sodium**, a chemical compound. The product is available in two dosages: 1 g and 3 g of powder, which is reconstituted into a solution for intravenous administration. The maximum daily dose is 12 g, with a total maximum dose of 600 g over a treatment period not exceeding 7 days. The medication is manufactured by MEDA AB and is authorized for use in Sweden. Participant compliance with the dosing schedule will be monitored throughout the trial.

The comparator treatment in this study is **Cloxacillin Navamedic**, also formulated as a **solution for injection/infusion**. The active substance is **cloxacillin**, another chemical compound. This product is provided as a 2 g powder for reconstitution into a solution for intravenous administration. Similar to the experimental treatment, the maximum daily dose is 12 g, with a total maximum dose of 600 g over a 7-day treatment period. NAVAMEDIC ASA is the manufacturer, and the product is authorized for use in Sweden. Compliance with the dosing regimen will be closely monitored to ensure adherence to the study protocol.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is defined as the proportion of patients who are alive at day 90 without complications. Complications are specified as relapse within 90 days from the completion of antibiotic treatment, or the need for a change or addition of antibiotic treatment due to adverse events or clinical failure. The trial aims to compare the clinical outcomes in patients with penicillin-susceptible **Staphylococcus aureus** bacteraemia treated with bensylpenicillin versus cloxacillin. The efficacy parameters will be collected and analyzed at the specified timepoint of day 90 post-treatment. The trial will utilize a randomized controlled design to ensure the reliability and validity of the efficacy assessments.