Evaluation of Clindamycin Hydrochloride and Drug Combination on 90-Day Mortality in Patients with Staphylococcus aureus Bacteremia

The primary objective of the Staphylococcus aureus Network Adaptive Platform trial (SNAP) is to evaluate the effect of various interventions on **all-cause mortality** at 90 days in patients with **Staphylococcus aureus bacteremia** (SAB). This objective is clinically significant as it aims to determine the most effective treatment strategies to reduce mortality in this serious bloodstream infection, which is associated with high morbidity and mortality rates.

Secondary objectives include examining the impact of these interventions on several endpoints:

• Mortality
• Hospital length of stay
• Treatment failure
• Treatment complications
• Healthcare costs

The clinical trial focuses on patients diagnosed with **Staphylococcus aureus bacteremia**. The study population includes both male and female participants, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. The trial does not specifically target a vulnerable population. Participants were selected based on the presence of the Staphylococcus aureus complex in at least one blood culture and their admission to a participating hospital at the time of eligibility assessment. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. The trial aims to evaluate the effect of various interventions on all-cause mortality at 90 days in patients with this condition.

The clinical trial is designed to evaluate the effect of various interventions on **all-cause mortality** at 90 days in patients with **Staphylococcus aureus bacteremia**. This trial employs a **randomized, double-blind, controlled** methodology to ensure the reliability and validity of the results. The trial is expected to run from August 2023 to September 2026, with participant involvement lasting up to 90 days. The study includes several antibiotics, such as **clindamycin hydrochloride**, **levofloxacin**, and **flucloxacillin**, administered either orally or intravenously, depending on the specific medication.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as the presence of **Staphylococcus aureus** in blood cultures and hospital admission status. Follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment regimen, and any adverse reactions. The end-of-study visit will occur at the conclusion of the 90-day period, where final assessments will be conducted to evaluate the primary and secondary endpoints, including mortality rates and microbiological treatment outcomes.

The expected length of participant involvement is 90 days, during which they will be closely monitored for any serious adverse reactions or other conditions that may necessitate early termination from the study. Such conditions include significant deviations from the protocol or the occurrence of severe adverse events that compromise participant safety. The trial's primary endpoint is the measurement of all-cause mortality at 90 days, while secondary endpoints include mortality at earlier time points, duration of survival, and length of hospital stay. The trial also aims to assess the health economic costs and the proportion of participants returning to their usual level of function by day 90.

The clinical trial involves the administration of several **antibiotics** to evaluate their effects on all-cause mortality at 90 days in patients with Staphylococcus aureus bacteremia (SAB). The experimental medications include **Clindamycin Hydrochloride**, which is provided in a hard capsule form for oral administration. The maximum daily dose is 1800 mg, with a total maximum dose of 162,000 mg over a treatment period of up to 90 days.

**Levofloxacin** is administered as a film-coated tablet, also taken orally. The maximum daily dose is 1000 mg, with a total maximum dose of 90,000 mg over a 90-day period.

**Flucloxacillin** is provided as a powder for solution for injection or infusion, administered intravenously. The maximum daily dose is 12 g, with a total maximum dose of 1080 g over a 3-day treatment period.

**Cefazolin** is available as a solution for injection or infusion, administered intravenously. The maximum daily dose is 8 g, with a total maximum dose of 720 g over a 3-day period.

**Co-trimoxazole** is administered in tablet form orally, with a maximum daily dose of 3840 mg and a total maximum dose of 345,600 mg over 90 days.

**Doxycycline** is provided in a hard capsule form for oral administration. The maximum daily dose is 200 mg, with a total maximum dose of 18,000 mg over a 90-day period.

**Moxifloxacin** is administered as a film-coated tablet orally, with a maximum daily dose of 400 mg and a total maximum dose of 36,000 mg over 90 days.

**Vancomycin** is available as a concentrate for solution for infusion, administered via IV infusion. The maximum daily dose is 6 g, with a total maximum dose of 540 g over a 3-day period.

**Linezolid** is administered as a film-coated tablet orally, with a maximum daily dose of 1200 mg and a total maximum dose of 108,000 mg over 90 days.

**Benzylpenicillin Sodium** is provided as a powder for solution for infusion, administered intravenously. The maximum daily dose is 24 g, with a total maximum dose of 2160 g over a 3-day period.

**Amoxicillin** is administered as a dispersible tablet orally, with a maximum daily dose of 3000 mg and a total maximum dose of 270,000 mg over 90 days.

**Cefalexin** is available in capsule form for oral administration. The maximum daily dose is 4000 mg, with a total maximum dose of 360,000 mg over a 90-day period.

**Clindamycin** is provided as a solution for injection, administered intravenously. The maximum daily dose is 1800 mg, with a total maximum dose of 9 g over a 5-day period.

**Daptomycin** is administered as a powder for solution for injection or infusion, intravenously. The maximum daily dose is 10 mg/kg, with a total maximum dose of 90 g over a 3-day period.

**Rifampicin** is provided in a hard capsule form for oral administration. The maximum daily dose is 900 mg, with a total maximum dose of 81,000 mg over a 90-day period.

All medications are administered according to the specified dosing schedules, and participant compliance is monitored throughout the trial. No non-experimental treatments, such as placebos or comparator treatments, are used in this study.

The efficacy of the clinical trial will be assessed using a range of primary and secondary endpoints. The primary endpoint is the **all-cause mortality** at 90 days after platform entry. Secondary endpoints include all-cause mortality at 14, 28, and 42 days after platform entry, duration of survival censored at 90 days, and various measures of hospital stay length. These include the length of stay of acute index inpatient hospitalization and total index hospitalization, both truncated at 90 days. Additionally, time to being discharged alive from the total index hospitalization will be measured, with all deaths within 90 days considered as '90 days'.

Other secondary endpoints involve microbiological treatment failure, defined as a positive sterile site culture for **Staphylococcus aureus** between 14 and 90 days after platform entry, and the diagnosis of new foci within the same timeframe. The presence of new foci will be determined by the site investigator using clinical, radiological, microbiological, and pathological findings. The occurrence of **C. difficile** diarrhea, serious adverse reactions, and health economic costs will also be evaluated. Functional outcomes will be assessed by the proportion of participants returning to their usual level of function at day 90, using the modified functional bloodstream infection score. Desirability of outcome rankings and total antibiotic days, as well as days alive and free of antibiotics, will be recorded in the 90 days following platform entry.