Evaluation of Intravenous Dalbavancin Versus Standard Antibiotic Regimen in Staphylococcus aureus Catheter-Related Bloodstream Infections

The primary objective of this study is to demonstrate that a single-dose of intravenous **dalbavancin** 1500 mg is non-inferior to standard documented antibiotic therapy administered for 14 days, in patients with non-complicated catheter-related bloodstream infections (CR-BSIs) due to **Staphylococcus aureus**. This evaluation is conducted at Day 30, which is the long follow-up visit. The clinical relevance of this objective lies in potentially reducing the treatment duration and hospital stay, thereby improving patient compliance and reducing healthcare costs.

Secondary objectives include:

• Assessing the cure rate at Day 14 and Day 90 (end of study).
• Evaluating the mortality rate within 90 days of follow-up.
• Determining the time to negativation of blood cultures.
• Assessing the patient's quality of life.
• Measuring the length of hospital stay.
• Conducting cost-utility analyses.
• Monitoring the occurrence of any adverse events, including adverse events (AE) and serious adverse events (SAE), until Day 90 (end of study).

The clinical trial focuses on patients with **catheter-related bloodstream infections** due to **Staphylococcus aureus**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a first blood culture positive for **S. aureus** obtained within 96 hours before randomization. The trial does not include a vulnerable population. The total number of participants is not provided by the sponsor. Participants must have an intravascular catheter, such as an implantable venous access device, removed before randomization. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include the presence of non-complicated **CR-BSIs** and the ability to provide informed consent. The selection process ensures that participants meet these criteria, but further details on the selection methodology are not disclosed.

The clinical trial is designed as a **randomized**, open-label, controlled study to evaluate the efficacy of a single-dose intravenous **dalbavancin** compared to standard antibiotic therapy in patients with catheter-related bloodstream infections due to **Staphylococcus aureus**. The trial aims to demonstrate that a single 1500 mg dose of dalbavancin is non-inferior to a 14-day course of standard antibiotic therapy, as per national guidelines, by Day 30. The study will involve two parallel groups, with participants randomly assigned in a 1:1 ratio to receive either the test or comparator treatment. The trial is expected to run from June 2023 to September 2026, with participant involvement lasting up to 90 days.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age (at least 18 years), a positive blood culture for **S. aureus** within 96 hours before randomization, and removal of the intravascular catheter before randomization. The primary endpoint is clinical cure without relapse at Day 30, defined by the absence of infection signs, relapse of bacteremia, or additional antibiotic therapy. Secondary endpoints include clinical cure at Day 14 and Day 90, all-cause mortality within 90 days, and quality of life assessments using the EQ-5D-5L scale at baseline, Day 14, Day 30, and Day 90.

Follow-up visits will occur at Day 14, Day 30, and Day 90, with the end-of-study visit at Day 90. Participants will be monitored for adverse events, hospitalization duration, and cost-effectiveness measures such as cost per avoided relapse and quality-adjusted life years. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that necessitate discontinuation of the study drug. The trial is conducted in compliance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants.

The clinical trial involves the administration of **dalbavancin**, marketed as Xydalba, which is provided as a 500 mg powder for concentrate for solution for infusion. The experimental medication is administered intravenously as a single dose of 1500 mg. The pharmaceutical form is a solution for infusion, and the treatment period is limited to one day. This medication is being evaluated for its efficacy in treating catheter-related bloodstream infections due to Staphylococcus aureus.

In addition to the experimental treatment, the trial includes several comparator treatments, which are standard antibiotic therapies administered according to national guidelines for a duration of 14 days. These include **oxacillin**, administered via infusion with a maximum daily dose of 12 g and a total dose of 168 g. **Teicoplanin** is administered either through intravenous infusion or intramuscular injection, with a maximum daily dose of 6 mg/kg and a total dose of 84 mg/kg. **Delafloxacin** is provided in both oral and intravenous forms, with a maximum daily dose of 900 mg and a total dose of 12,600 mg.

**Ciprofloxacin** is administered orally and intravenously, with a maximum daily dose of 1200 mg and a total dose of 16,800 mg. **Tigecycline** is administered via infusion, with a maximum daily dose of 100 mg and a total dose of 750 mg. **Lymecycline** is administered orally, with a maximum daily dose of 600 mg and a total dose of 8400 mg. **Pristinamycin** is also administered orally, with a maximum daily dose of 3000 mg and a total dose of 42,000 mg.

**Cloxacillin** is administered via infusion, with a maximum daily dose of 12 g and a total dose of 168 g. **Piperacillin and beta-lactamase inhibitor** are administered via infusion, with a maximum daily dose of 16 g and a total dose of 224 g. **Ceftriaxone** is administered via infusion, with a maximum daily dose of 2 g and a total dose of 28 g. **Doxycycline** is administered both orally and intravenously, with a maximum daily dose of 200 mg and a total dose of 1500 mg.

**Amikacin** is administered intravenously, with a maximum daily dose of 45 mg/kg and a total dose of 45 mg/kg. **Cefazolin** is administered via infusion, with a maximum daily dose of 3 g and a total dose of 42 g. **Amoxicillin** is administered both orally and intravenously, with a maximum daily dose of 12 g and a total dose of 168 g. **Levofloxacin** is administered both orally and intravenously, with a maximum daily dose of 1000 mg and a total dose of 14,000 mg.

**Sulfamethoxazole and trimethoprim** are administered both orally and intravenously, with a maximum daily dose of 2400 mg and a total dose of 33,600 mg. **Daptomycin** is administered via infusion, with a maximum daily dose of 6 mg/kg and a total dose of 84 mg/kg. **Linezolid** is administered both orally and intravenously, with a maximum daily dose of 1200 mg and a total dose of 16,800 mg. **Clindamycin** is administered both orally and intravenously, with a maximum daily dose of 2400 mg and a total dose of 33,600 mg.

**Ofloxacin** is administered both orally and intravenously, with a maximum daily dose of 600 mg and a total dose of 8400 mg. **Tedizolid** is administered orally, with a maximum daily dose of 200 mg and a total dose of 2800 mg. **Rifampicin** is administered both orally and intravenously, with a maximum daily dose of 30 mg/kg and a total dose of 420 mg/kg. **Ceftaroline fosamil** is administered via infusion, with a maximum daily dose of 1800 mg and a total dose of 25,200 mg.

**Vancomycin** is administered via infusion, with a maximum daily dose of 6 g and a total dose of 84 g. **Amoxicillin and beta-lactamase inhibitor** are administered both orally and intravenously, with a maximum daily dose of 600 mg and a total dose of 8400 mg. **Cefotaxime** is administered via infusion, with a maximum daily dose of 6 g and a total dose of 86 g. **Gentamicin** is administered via infusion, with a maximum daily dose of 8 mg/kg and a total dose of 8 mg/kg.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the **clinical cure without relapse at Day 30**, which is defined by the absence of local and/or general signs of infection, relapse of bacteremia to *Staphylococcus aureus*, and any additional antibiotic therapy active on *S. aureus* received between Day 0 and Day 14 in the dalbavancin arm, or between Day 14 and Day 30 in both arms. Additionally, the absence of deep focus infection, including endocarditis, and death from all causes will be considered.

Secondary endpoints include clinical cure at Day 14 and Day 90 (end of study), all-cause mortality within 90 days of follow-up, and the time from the first positive blood culture to the first negative blood cultures, limited to Day 14. Patient autonomy, pain, and anxiety will be evaluated using the EQ-5D-5L scale at baseline (Day 0), Day 14, Day 30, and Day 90. Other secondary measures include hospitalization duration, cost per avoided relapse, life-year gained, and per quality-adjusted life year (QALY), as well as the proportion of patients experiencing any adverse event until the end of the study, including complications due to venous catheterization.