Evaluation of Systemic Antibiotic Prophylaxis with Piperacillin-Tazobactam and Cefazolin in Excision-Autograft Surgery for Burn Patients: A Multicenter Randomized Study

The primary objective of this study is to evaluate the impact of **systemic antibiotic prophylaxis** on postoperative infections, sepsis, and autograft lysis requiring new skin autograft within 7 days postoperatively in patients undergoing excision-autograft surgery for burns. This is clinically relevant as it aims to reduce postoperative complications, which can significantly affect patient recovery and healthcare resources.

Secondary objectives include: - To evaluate the impact on 90-day mortality. - To evaluate the impact on antibiotic consumption. - To evaluate the impact on the duration of hospitalization until complete healing (> 95% total burn surface area). - To evaluate the impact on the duration of hospitalization living without antibiotic therapy. - To evaluate the impact on colonization by multidrug-resistant bacteria during hospital stay.

The clinical trial involves a study population of **burn patients** who have undergone excision-autograft surgery. The trial includes both male and female participants, all of whom are adults over the age of 18. The participants are required to have a total body surface area (TBSA) burn between 5% and 40%. The trial population is selected based on the necessity for at least one excision-graft surgery, and participants must provide signed informed consent or be included under emergency provisions as per legal requirements. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that special ethical considerations are in place to protect the participants involved.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the impact of systemic antibiotic prophylaxis on postoperative infections, sepsis, and autograft lysis in burn patients undergoing excision-autograft surgery. The trial aims to assess the efficacy of **piperacillin sodium** and **tazobactam sodium** in comparison to a placebo and **cefazolin**. The study is expected to run from October 2020 to July 2026, with participant involvement lasting up to 90 days post-surgery.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (over 18 years), burn total body surface area (TBSA) between 5% and 40%, and the requirement for excision-graft surgery. Informed consent will be obtained, or inclusion will occur under emergency provisions. Following the screening, participants will be randomized to receive either the active treatment or placebo. The primary endpoint is the occurrence of postoperative infection, defined as sepsis, surgical site infection, or autograft lysis requiring a new autograft within 7 days post-surgery.

Secondary endpoints include 90-day mortality, skin graft lysis requiring a new procedure, postoperative pulmonary infection, and the number of hospitalization days until complete healing. Follow-up visits will occur at 28 and 90 days to assess these outcomes, including the presence of multiresistant bacterial colonization. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any adverse events are addressed.

Participants may be withdrawn from the study early if they experience significant adverse reactions, withdraw consent, or if the investigator deems it necessary for their safety. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **Piperacillin Tazobactam Viatris**, a combination of **piperacillin sodium** and **tazobactam sodium**. This experimental medication is provided in the form of a powder for solution for infusion, specifically designed for intravenous injection. The dosage regimen includes a maximum daily dose of 4 grams, with a total maximum dose of 8 grams over the treatment period. The administration is conducted intravenously, ensuring direct delivery into the bloodstream. The pharmaceutical form is a solution for infusion, and the treatment is not formulated for pediatric use. The active substances are of chemical origin, and the product is authorized under the marketing authorization number NL 33055 in France.

The study also includes a **placebo** comparator, labeled as "Placebo de Cefazoline / Piperaciline / Tazobactam." This placebo is utilized to maintain the double-blind nature of the trial, ensuring unbiased results. The placebo does not contain any active substances and is not associated with a specific pharmaceutical form or route of administration. It serves as a control to evaluate the efficacy and safety of the experimental treatments.

Additionally, **Cefazolin** is used as a comparator treatment in the trial. Cefazolin is provided as a powder for solution for injection or infusion, with a maximum daily dose of 2 grams and a total maximum dose of 4 grams over the treatment period. The administration route is intravenous infusion, allowing for efficient systemic distribution. Cefazolin is a chemical substance and is not formulated for pediatric use. The product is identified by the scientific product evaluation code SUB07379MIG.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the occurrence of post-operative infection, which is defined as post-operative **sepsis**, surgical site infection, and/or autograft lysis requiring a new autograft within 7 days after surgery. Secondary endpoints include 90-day mortality, skin graft lysis necessitating a new autograft procedure, post-operative pulmonary infection, the number of hospitalization days until complete healing (defined as more than 95% total burn surface area), the number of hospitalization days living without antibiotic therapy at day 28 and day 90, and colonization or infection with multiresistant bacteria at day 28 and day 90.