PROPHY-SEIN: Randomized Double‑Blind Non‑Inferiority Trial of Cefazolin Prophylaxis vs Placebo for Surgical Site Infection Prevention in Breast‑Conserving Surgery

The primary objective is to demonstrate the non‑inferiority of placebo compared with standard antibiotic prophylaxis using cefazolin, administered in a double‑blind fashion within one hour before breast lumpectomy, with respect to the incidence of any surgical site infection within 30 days post‑operatively, thereby assessing the necessity of routine prophylaxis in this surgical context.

• If non‑inferiority is not established, the principal secondary objective is to evaluate the superiority of cefazolin for reducing the incidence of any surgical site infection at day 30, following FDA guidance for multiple endpoints.
• Incidence of superficial and deep surgical site infections at day 30.
• Incidence of surgical site infection at day 30 stratified by simple lumpectomy versus lumpectomy with sentinel lymph node procedure.
• Incidence of surgical site infection at day 30 in patients with and without pre‑operative tumour localisation using percutaneous devices.
• Occurrence and severity of postoperative complications, classified by the Clavien‑Dindo system, including septic complications such as sepsis or septic shock.
• Management strategies for infections occurring within 30 days, including outpatient versus inpatient care, local treatment alone, oral or parenteral antibiotics, and need for revision surgery.
• Occurrence of major adverse events potentially related to cefazolin during the intra‑ and postoperative periods up to day 30, such as anaphylactic reactions, prolonged hospitalization, ICU admission, or death.
• Delay before initiation of adjuvant chemotherapy and/or radiotherapy when indicated by the treating oncologist.

The trial enrolled adult female patients (≥ 18 years) undergoing breast lumpectomy or partial mastectomy, with or without sentinel lymph node evaluation, who were beneficiaries of the Social Security system and provided informed consent. Participants were required to have a diagnosis of Breast Cancer and were otherwise considered suitable for elective surgical intervention. The sponsor did not provide information on the total number of participants. Selection was based on meeting the principal inclusion criteria, while no specific lifestyle restrictions such as diet or physical activity were stipulated in the provided data. Exclusion criteria were not detailed in the source material.

The study is a prospective, randomized, double‑blind, placebo‑controlled, non‑inferiority trial evaluating prophylactic cefazolin versus placebo administered within one hour before breast lumpectomy for breast cancer. Participants undergo a screening visit to confirm eligibility, are randomized 1:1 to receive either cefazolin (1 g or 2 g IV) or matching placebo (0.9 % NaCl), and receive the assigned study drug intravenously immediately prior to skin incision. Follow‑up visits are scheduled on postoperative day 3 (clinical assessment), day 7 (wound evaluation), and day 30 (primary endpoint assessment), with the end‑of‑study visit occurring at day 30 to record the occurrence of any surgical site infection. Participant involvement therefore extends from the screening visit through day 30 post‑surgery, approximately 4–5 weeks. Early termination may occur if the participant withdraws consent, experiences a serious adverse event attributable to the study drug, requires unblinded rescue antibiotics, or is lost to follow‑up. Recruitment is planned to begin 1 July 2026 and to conclude by 1 July 2028, with each subject remaining in the trial for the 30‑day postoperative period.

The investigational arm utilizes cefazolin sodium supplied as two pharmaceutical presentations: a 1 g powder for solution for injection/infusion and a 2 g powder for solution for injection (IM‑IV). Both products are administered intravenously as a single dose within the hour preceding skin incision for lumpectomy. The assigned dose (1 g or 2 g) is delivered as an IV bolus or short infusion according to the study protocol, with the infusion completed before the start of surgical dissection.

The placebo comparator consists of 0.9 % sodium chloride solution (CHLORURE DE SODIUM VIAFLO) provided for intravenous infusion. It is administered in an equivalent volume and timing to the active drug, ensuring blinding of participants and surgical staff.

A second placebo formulation contains sodium chloride, potassium chloride, and sodium hydrogen carbonate in a 100 ml intravenous solution (SODIUM CHLORIDE). This product is infused intravenously in the same manner and schedule as the active antibiotic, matching the volume and infusion rate to preserve study masking.

All administrations are documented in the case report form, and infusion start and end times are recorded by study personnel. Compliance with the dosing schedule is monitored by the clinical team, and any deviation from the prescribed administration protocol is reported according to the trial’s safety monitoring procedures.

Efficacy will be evaluated primarily by determining the proportion of participants who develop any surgical site infection (SSI) within 30 days after breast lumpectomy or partial mastectomy. SSI classification (superficial versus deep) will follow the validated criteria established by the U.S. Centre for Disease Control and Prevention.

Secondary efficacy assessments will include the proportion of patients with each SSI type, stratified by surgical procedure (simple lumpectomy versus lumpectomy with sentinel lymph node biopsy) and by the use of pre‑operative tumour localisation devices. Additional secondary measures comprise the incidence, type, and severity of intra‑operative and postoperative adverse events attributed to the study drug or placebo (using the WHO causality scale), postoperative complications classified by the Clavien‑Dindo system, and related outcomes such as the need for additional antibiotic therapy, surgical revisions, prolonged hospital stay, readmission, sepsis, ICU admission, and time to initiation of adjuvant therapy. All‑cause and septic‑related mortality will also be recorded.