Hanssen Jaap L J, van Hulten Esther Y, Bos Pieter K, van der Jagt Olav P, Lammers A J Jolanda, Mahdad Rachid, Nolte Peter A, Peters Edgar J G, Poolman Rudolf W, Visser Jetze, Somford Matthijs P, Veerman Karin, Vehmeijer Stephan B W, Vlasveld Imro N, Zijlstra Wierd, van Geenen Rutger, Geurts Jan, Röling Maarten, Wouthuyzen-Bakker Marjan, Scheper Henk, de Boer Mark G J
Leiden University Center for Infectious Diseases (LU-CID), Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Leiden University Center for Infectious Diseases (LU-CID), Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Contemp Clin Trials. 2025 Aug;155:107972. doi: 10.1016/j.cct.2025.107972. Epub 2025 May 31.
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.
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 %.
Demonstrating non-inferiority of antimicrobial monotherapy during the oral treatment phase of DAIR would enable a more patient-tailored approach when managing sPJI.
利福平联合治疗目前是清创、抗生素及植入物保留（DAIR）治疗葡萄球菌性人工关节感染（sPJI）的首选口服抗菌方案。缺乏高质量证据证实这一推荐，且该方案药物停用率高，因此有必要研究替代抗菌策略。
葡萄球菌性人工关节感染口服抗菌治疗阶段利福平联合治疗与靶向抗菌单药治疗（RiCOTTA）试验是一项多中心、非劣效性、开放标签的随机对照试验，评估在采用DAIR治疗的sPJI口服治疗阶段单药治疗（不含利福平）与利福平联合治疗的效果。该试验目前正在18家医院招募患者。随机分组在从静脉治疗转为口服治疗前1至7天进行。抗生素总治疗时长为12周，总随访时间为15个月。符合条件的患者为采用DAIR治疗的膝部或髋部sPJI成年患者。主要结局是抗菌治疗结束一年后的治疗成功，定义为不存在以下情况：i. 与PJI相关的再次手术；ii. 在初始12周治疗后与PJI相关的抗生素治疗；iii. 随访结束时与PJI相关的持续使用抗生素；iv. 死亡。需要招募316名患者，以80%的检验效能、10%的非劣效界值，并基于估计85%的治疗成功率来证实单药治疗的非劣效性。
在DAIR的口服治疗阶段证明抗菌单药治疗的非劣效性，将使在管理sPJI时能采用更适合患者的方法。
