A Phase 3 interventional study of Cefazolin 2 g Infusion and Placebo infusion of .9 normal saline in Breast Cancer, Breast Surgery and Surgical Site Infection (SSI), sponsored by University Hospital, Clermont-Ferrand. Not yet recruiting at 33 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by University Hospital, Clermont-Ferrand · Phase 3, Interventional, and Prevention
The goal of this clinical trial is to determine whether preoperative antibiotic prophylaxis with cefazolin is necessary to prevent surgical site infections in adult women undergoing breast-conserving surgery (lumpectomy or partial mastectomy) for breast cancer. Specifically, the trial aims to establish whether surgery without antibiotic prophylaxis is non-inferior to surgery with cefazolin prophylaxis in terms of surgical site infections within 30 days after surgery.
The main questions it aims to answer are:
Researchers will compare preoperative cefazolin prophylaxis (2 g administered intravenously) with placebo (0.9% saline solution) to determine whether surgery without antibiotic prophylaxis is non-inferior to surgery with cefazolin prophylaxis in preventing surgical site infections. A total of 1,600 participants will be randomly assigned to one of the two groups. Neither the participants nor the healthcare professionals involved in their care will know which treatment has been administered.
Participants will:
No additional hospital visits are required specifically for the study.
Background and Rationale
Breast-conserving surgery is the reference treatment for early-stage breast cancer and is performed in a large proportion of women undergoing surgery for this condition. Although surgical antibiotic prophylaxis (SAP) is widely used to prevent surgical site infections (SSIs), its benefit specifically in breast-conserving surgery remains uncertain.
Available evidence is limited by the relatively small number of randomized controlled trials, the inclusion of heterogeneous breast surgical procedures, and differences in antibiotic prophylaxis regimens. Many previous studies included patients undergoing more extensive procedures, such as total mastectomy or axillary lymph node dissection, which may carry different risks of postoperative infection. Consequently, the benefit of routine antibiotic prophylaxis in patients undergoing breast-conserving surgery alone has not been clearly established.
Although generally well tolerated, antibiotic prophylaxis may cause adverse drug reactions, including hypersensitivity reactions, and contribute to alterations in the gut microbiota and the selection of antimicrobial resistance. Avoiding unnecessary antibiotic exposure is therefore an important objective of antimicrobial stewardship, particularly for frequently performed surgical procedures.
Study Design and Methodology
PROPHY-SEIN is a multicenter, randomized, double-blind, placebo-controlled non-inferiority trial designed to provide robust evidence regarding the need for routine SAP in breast-conserving surgery for cancer.
Randomization is performed in a 1:1 ratio, with stratification by participating center and whether a sentinel lymph node procedure is performed. Treatment allocation is concealed from participants, surgeons, anesthesiologists, and study investigators. Study treatments are prepared by healthcare personnel not involved in the participants' perioperative management or postoperative assessment, ensuring that the administered solutions are indistinguishable.
The non-inferiority margin is set at an absolute difference of 2 percentage points in the incidence of SSIs. This margin represents the maximum additional risk of infection considered clinically acceptable with a strategy without antibiotic prophylaxis. Its selection reflects the relatively low incidence of SSIs after breast-conserving surgery, their predominantly superficial nature, and the potential benefits of reducing unnecessary antibiotic exposure.
The primary analysis will assess non-inferiority using the Farrington-Manning method, with a one-sided significance level of 2.5%. Analyses will be conducted in both the intention-to-treat and per-protocol populations, with consistent findings required to establish non-inferiority. If non-inferiority is not demonstrated, a prespecified secondary analysis will assess whether cefazolin is superior to placebo in preventing SSIs.
To minimize assessment bias, suspected SSIs will be independently reviewed by a blinded adjudication committee comprising experts in anesthesiology, surgery, and infectious diseases, using predefined diagnostic criteria.
Expected Contribution
PROPHY-SEIN is intended to address an important evidence gap in perioperative care for breast cancer surgery. By focusing specifically on breast-conserving procedures and using a rigorous randomized, double-blind design, the trial aims to clarify whether routine antibiotic prophylaxis provides a clinically meaningful benefit in this setting.
The findings may help inform future clinical practice guidelines and support a more evidence-based approach to antibiotic prophylaxis, balancing the prevention of postoperative infections against the individual and collective consequences of unnecessary antibiotic exposure.
12,844 studies on the registry are indexed under Breast Neoplasms; 2,939 are open to participants now.
This study's planned enrollment of 1,600 is above the median of 72 across 9,517 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →University Hospital, Clermont-Ferrand is the lead sponsor of 856 studies on the registry; 180 are open to participants now.
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Exclusion Criteria:
Administration of preoperative surgical antibiotic prophylaxis with cefazolin
Drug: Cefazolin 2 g Infusion
Administration of a placebo identical in appearance to the cefazolin preparation, without antibiotic prophylaxis.
Drug: Placebo infusion of .9 normal saline
Cefazolin 2 g diluted in 100 mL of 0.9% sodium chloride solution, administered intravenously within one hour before surgical incision. An additional dose of 1 g may be administered if surgery lasts more than 4 hours.
100 mL of 0.9% sodium chloride solution, administered intravenously within one hour before surgical incision. An additional 100 mL may be administered if surgery lasts more than 4 hours. The placebo is indistinguishable from the cefazolin preparation.
Proportion of patients with any surgical site infection (SSI)
Time frame: within 30 days after surgery
Proportion of patients with superficial SSI and deep SSI
Time frame: within 30 days after surgery
Proportion of SSI among patients operated on for simple lumpectomy and for lumpectomy combined with a sentinel lymph node procedure
Time frame: within 30 days after surgery
Proportion of SSI among patients with and without preoperative localisation of the tumour using a percutaneous device, such as metal wire
Time frame: within 30 days after surgery
Proportion, type and severity of postoperative complications, according to the Clavien and Dindo classification, and the proportion of patients with postoperative sepsis or septic shock
Time frame: within 30 days after surgery
The medical and/or surgical management of any SSI including outpatient/hospital management, local care alone or need for oral/parenteral curative antibiotic therapy, and/or need for revision surgery, need for additional scare or reopening, etc.
Time frame: Management, even delayed, of any SSI occurring within 30 days after initial surgery
Proportion, type and severity (minor, moderate, severe, lethal) of intraoperative and postoperative adverse events potentially attributable to cefazolin or its placebo, and their causality according to the WHO scale
Time frame: within 30 days after surgery
Duration of index hospital stay and whether the index stay had to be prolonged, notably due to the occurrence of a SSI
Time frame: within 30 days after surgery
Need for an unexpected medical or surgical consultation or hospital readmission for a suspected or confirmed SSI
Time frame: within 30 days after surgery
Need for an unexpected admission to the ICU
Time frame: within 30 days after surgery
All-causes and septic-related mortality
Time frame: within 30 days after surgery
The time (in days) to initiation of the adjuvant treatment (chemotherapy and/or radiotherapy, etc.) (if indicated by the attending oncologist)
Time frame: Up to day 60 after surgery
Plan to share: Yes — De-identified individual participant data underlying the results reported in the primary publication may be shared with qualified researchers for scientifically justified research purposes, subject to approval by the study sponsor. Data will not be made publicly available or routinely provided as supplementary material to the publication. Access conditions are detailed in the Access Criteria section.
Supporting information: Study protocol, Statistical analysis plan
Time frame: From publication of the primary study results in a peer-reviewed journal until 3 years after publication.
Access criteria: De-identified individual participant data underlying the published results may be made available to qualified researchers upon reasonable request to the study sponsor. Requests must include a scientifically sound research proposal specifying the objectives, methodology, and data required. Each request will be reviewed by the study sponsor and investigators. Access will be granted only for approved research purposes, subject to applicable ethical and legal requirements, including data protection regulations, and the execution of a data-sharing agreement where appropriate.
No publications or documents are linked to this record.
Start is estimated for Nov 2026; primary completion for Nov 2028, 24 months later.
Of 293 non-industry phase 3 interventional studies under Breast Neoplasms, half reached primary completion within 80 months of starting (the median), counting those still running; a quarter within 51 and three quarters within 128. This study's planned 24 months is below that.
Counting every sponsor, half of 540 studies reached it within 58 months; a quarter within 34 and three quarters within 96.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Cefazolin
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