NCT05211011Unknown4 期
Efficacy and Safety of Intravenous Fosfomycin in Prosthetic Joint Infection (PJI) Caused by Staphylococci, Streptococci, Enterococci and Gram-negative Bacilli, Including Mixed Infections and Culture Negative PJI's ("PROOF-Study")
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 入组人数
- 226
- 试验地点
- 16
- 主要终点
- Infection cure rate
研究概览
简要总结
The PROOF Study is an open prospective interventional non-randomized study which aim is to determine the outcome / effect and safety of fosfomycin in patients with hip, knee or shoulder PJI.
详细描述
To confirm a non-inferior effect and the safety of the investigated antimicrobial fosfomycin regimen in PJI of the hip, knee or shoulder against an assumed 80% effect (PJI-free proportion within one year for standard antibiotics aside fosfomycin), following a standardized surgical therapy involving retention, one-stage exchange or two-stage exchange (with short or long interval).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent has been obtained (prior to planned surgical PJI treatment);
- •Subject is ≥18 years of age;
- •Subject has either a culture negative or a culture positive PJI of the hip, knee or shoulder prosthesis: (i) visible purulence of a preoperative aspirate or intraoperative periprosthetic tissue (as determined by the surgeon),or (ii) presence of a sinus tract communicating with the prosthesis, or (iii) acute inflammation in intraoperative permanent tissue sections by histopathology (as determined by the pathologist), or (iv) microbial growth in preoperative joint aspirate, intraoperative periprosthetic tissue or sonication fluid of the removed implant (>50 CFU/ml sonication fluid), or (v) synovial fluid with >2000 leukocytes/μl or >70% granulocytes; or reasonable evidence for a suspected PJI (based on clinical, laboratory, and radiological criteria) to undergo joint surgery to proof the PJI diagnosis (according to standard of care, Zimmerli W et al. NEJM 2004);
- •For culture positive PJI's at least one of the following isolates:
- •staphylococci (fosfomycin MHK ≤ 32 mg/ml), streptococci (MHK ≤ 128 mg/ml), enterococci (MHK ≤ 128 mg/ml), fosfomycin susceptible gram-negative bacilli, including also mixed infections with other pathogens (fosfomycin susceptible or not);
- •Subject is planned to/will undergo appropriate surgical procedure following the state of the art PJI treatment algorithm, which includes either debridement & retention of the prosthesis or exchange of the prosthesis. The exchange includes a one-stage exchange, two-stage prosthesis exchange with a short interval (2- 3 weeks) or long interval (6-8 weeks), according to the treatment algorithm;
- •Subject is willing to participate in the study, follow protocol study treatment regimen, and comply with all planned follow-up assessments.
排除标准
- •Allergy or intolerance (or other contraindication) to fosfomycin;
- •Isolation of fungi (molds or yeasts) or mycobacteria;
- •Isolation of one of the following pathogens: staphylococci fosfomycin MHK > 32 mg/ml, streptococci MHK > 128 mg/ml, enterococci MHK > 128 mg/ml , fosfomycin resistant gramnegative bacilli;
- •Severely compromised bone/soft tissue pre or during surgery (if during surgery: exclusion/withdrawalbefore IMP application);
- •Pregnancy, and/or woman wishing to become pregnant;
- •Breast-feeding;
- •Women of childbearing potential without at least one of the following contraception methods: correctly placed coopercontaining or progestin-containing intrauterine device (IUD); female condom used WITH a spermicide (i.e. foam gel, film, cream, or suppository); bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure (at least till the end of the ambulatory treatment phase);
- •Subject has been previously enrolled in this study or was enrolled in another interventional medicinal product or medical device study in the last 30 days;
- •Subject had prior exposure to fosfomycin within the past 4 weeks;
- •Inability to read and understand the participant's information;
- •Subjects institutionalized by warrant or court order;
- •Employees of the sponsor or an involved CRO;
- •In pre surgery culture negative patients: All isolates unsusceptible to fosfomycin after surgery (exclusion / early withdrawal after surgery);
- •Suspected PJI not proven after surgery (exclusion / early withdrawal after surgery).
研究组 & 干预措施
Fosfomycin Arm
Experimental
Include intravenous fosfomycin in the treatment of PJI according to predetermined algorithm
干预措施: Fosfomycin (Drug)
结局指标
主要结局
Infection cure rate
时间窗: 1 year
Proportion of patients free of PJI relapse (i.e. infection cure rate) within 1 year after inclusion. Relapse is defined as new PJI diagnosis more than 4 weeks after the last surgical intervention of the initial 12 week treatment period.
次要结局
- Infection cure rate(2 years)
- Proportion of patients with treatment failure(1 year)
- Safety and tolerability of fosfomycin(1 year)
- EQ5D5L(1 year)
- Peak Plasma Concentration (Cmax)(1 year)
- Proportion of patients with revision due to hematogenous versus non-hematogenous infection(1 year)
- Proportion of patients with implant failure(1 year)
- Proportion of patients with revision(1 year)
- Proportion of patients with aseptic revision(1 year)
- Proportion of patients with unscheduled early revisions(1 year)
- Proportion of patients with initially sufficient versus insufficient primary therapy(1 year)
- Specific functional joint scores(1 year)
研究者
Andrej Trampuz
Principle Investigator
Charite University, Berlin, Germany
研究点 (16)
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