Effect of Single versus Multiple Prophylactic Antibiotic Doses on Revision Rates due to Infection after Total Hip Arthroplasty: Protocol for A Target Trial Emulation Study Using Danish National Registries

IntroductionProphylactic 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. ObjectiveTo 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. DesignAn 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. SettingAll departments of orthopedic surgery in Denmark, from January 1st, 2010, to December 31st, 2020. ParticipantsPatients 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. InterventionA single dose of preoperatively administered prophylactic antibiotic administered preoperatively. ComparatorMultiple doses of prophylactic antibiotics administered within 24 hours of THA. OutcomesThe 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. AnalysesAnalyses 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). MotivationWe believe that the results of this trial will deliver important knowledge on optimal antibiotic prophylaxis dosage practice for primary THA.