Introduction Prophylactic antibiotics can reduce the risk of prosthetic joint infection (PJI), which is among the most severe complications following total hip arthroplasty (THA). Despite its importance, there is no consensus on the duration of prophylactic antibiotics, and current recommendations describe the use of either one single dose or up to 24 hours with multiple doses as options for antibiotic prophylaxis.

Objective To compare a single dose versus multiple doses of prophylactic antibiotics administered within 24 hours, on the risk of revision due to infection within the first 90 days after THA. Noninferiority will be demonstrated if the upper limit of the two-sided 95% confidence interval for the odds ratio is less than 1.4 for the single dose compared with multiple doses of antibiotic prophylaxis administered within 24 hours of the index surgery.

Design An emulated target trial combining data from the Danish Hip Arthroplasty Register and the Danish Microbiology Database naively assuming that operated patients were randomized to either single dose or multiple doses of prophylactic antibiotics administered within 24 hours.

Setting All departments of orthopedic surgery in Denmark, from January 1st, 2010, to December 31st, 2020.

Participants Patients with age ≥18 years, undergoing primary THA for all reasons except due to acute or sequelae from proximal femoral or pelvic fractures or bone tumor or metastasis will be included.

Intervention A single dose of preoperatively administered prophylactic antibiotic administered preoperatively.

Comparator Multiple doses of prophylactic antibiotics administered within 24 hours of THA.

Outcomes The primary outcome is the revision rates due to infection within 90 days after primary THA. Secondary outcomes within the first 90 days post-surgery include (i) risk of revision due to infection after primary THA (i) any revision after THA (ii) risk of potential PJI (iii) hospital-treated infections, (iv) community-based antibiotic use, and (v) mortality rate and furthermore, within 365 days post-surgery (vi) risk of revision due to infection after primary. All outcome measures will be extracted from national databases.

Analyses Analyses will be based on the Intention to Treat (ITT) population (i.e., all patients having a THA where some dose regimen of antibiotics is registered). The main analyses will explicitly emulate the components of the target trial protocol using the observational data. Based on the eligible individuals, assigned to a treatment strategy based on their data, following them from treatment assignment (time zero) until outcome or the end of follow-up (90 and 365 days from surgery, respectviely), and conducting the same analysis as the target trial. However, we will adjust for baseline confounders to approximate random treatment assignment and balance baseline demographic and clinical characteristics (i.e., pre-surgery covariates), we will use stabilized inverse probability treatment weighting (sIPTW).

Motivation We believe that the results of this trial will deliver important knowledge on optimal antibiotic prophylaxis dosage practice for primary THA.

The authors have declared no competing interest.

NO funding was received for this project

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The project was registered according to Danish legislation. No other ethical approval was required. Data is treated confidentially according to Danish data protection rules.The data for this study is stored on the servers of Statistics Denmark.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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The data presented in this study is stored on the servers of Statistics Denmark. Due to the rules for data protection at Statistics Denmark, it is not possible to share the data, neither in raw nor in anonymized form. However, other researchers can apply for permission to access the same raw data at Statistics Denmark.