Rifampicin combination therapy versus targeted antimicrobial monotherapy in the oral antimicrobial treatment phase of staphylococcal prosthetic joint infection (RiCOTTA-trial): protocol for a randomized, controlled, open-label, non-inferiority trial

Abstract

Background: Rifampicin-combination therapy is currently the first-choice oral antimicrobial regimen for staphylococcal prosthetic joint infections (sPJI) treated by debridement, antibiotics and implant retention (DAIR). Lack of high quality evidence to substantiate this recommendation and a high drug discontinuation rate of this regimen warrant investigation of alternative antimicrobial strategies.

Method: The Rifampicin Combination Therapy versus Targeted Antimicrobial Monotherapy in the Oral Antimicrobial Treatment Phase of Staphylococcal Prosthetic Joint Infection (RiCOTTA)-trial is a multicenter, non-inferiority, open-label, randomized controlled trial evaluating monotherapy (without rifampicin) versus rifampicin-combination therapy in the oral treatment phase of sPJI managed with DAIR. The trial is currently enrolling patients in 18 hospitals. Randomization takes place one to seven days before the switch from intravenous to oral therapy. Total antibiotic treatment duration is 12 weeks and the total follow-up time is 15 months. Eligible patients are adults with knee or hip sPJI managed by DAIR. Primary outcome is treatment success one year after finishing antimicrobial treatment, defined as the absence of: i. PJI related re-surgery, ii. PJI related antibiotic treatment after the initial treatment of 12 weeks, iii. PJI related ongoing use of antibiotics at end of follow-up, iv. Death. Enrolment of 316 patients is needed to confirm non-inferiority of monotherapy with a power of 80 %, non-inferiority margin of 10 % and based on an estimated treatment success of 85 %.

Conclusion: Demonstrating non-inferiority of antimicrobial monotherapy during the oral treatment phase of DAIR would enable a more patient-tailored approach when managing sPJI.

Keywords: Antimicrobial treatment; Prosthetic joint infection; Rifampicin; Staphylococcus.