Prosthetic joint infection of knee, hip or shoulder
Conditions
Interventions
Trade Name: INFECTOFOS® 5 g
Product Name: INFECTOFOS 5 g
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: FOSFOMYCIN
Sponsors
PRO-IMPLANT Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent has been obtained (prior to planned surgical PJI treatment); 2. Subject is =18 years of age; 3. 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); 4. 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); 5. 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; 6. Subject is willing to participate in the study, follow protocol study treatment regimen, and comply with all planned follow-up assessments. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 46 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: 1. Allergy or intolerance (or other contraindication) to fosfomycin; 2. Isolation of fungi (molds or yeasts) or mycobacteria ; 3. Isolation of at least one of the following pathogens: staphylococci MHK > 32 mg/ml, streptococci MHK > 128 mg/ml, enterococci MHK > 128 mg/ml, fosfomycin resistant gram-negative bacilli; 4. Severely compromised bone/soft tissue pre or during surgery (if during surgery: exclusion/withdrawal before IMP application); 5. Pregnancy, and/or women wishing to become pregnant; 6. Breast-feeding; 7. Women of childbearing potential* without at least one of the following contraception methods: correctly placed cooper-containing 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)**; 8. 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; 9. Subject had prior exposure to fosfomycin within the past 4 weeks; 10. Inability to read and understand the participant’s information; 11. Subjects institutionalized by warrant or court order; 12. Employees of the sponsor or an involved CRO; 13. In pre surgery culture negative patients: All isolates unsusceptible to fosfomycin after surgery (exclusion / early withdrawal after surgery); 14. Suspected PJI not proven after surgery (exclusion / early withdrawal after surgery).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To confirm the non-inferior effect and safety of the investigated antimicrobial fosfomycin regimen in prosthetic joint infection (PJI) of the hip, knee or shoulder against an assumed 80% efficacy (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). ;Secondary Objective: An additional objective is to characterize the population pharmacokinetic profile of fosfomycin in plasma to quantify inter- and intra-patient variability and to identify sources of variability in drug concentrations. ;Primary end point(s): Proportion of patients free of PJI-relapse within 1 year after inclusion (according to PJI definition, s. inclusion - only PJIs of the initially affected joint). ;Timepoint(s) of evaluation of this end point: Primary analysis after completion of the 1 year follow up data set. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of patients free of Prosthetic Joint-Infection relapse (infection cure rate) within 2 years after inclusion (according to PJI infection definition, s. below) • Proportion of patients with revision (surgical intervention with or without prosthesis removal >4 weeks after last surgical intervention of the initial 12 week treatment period) • Proportion of patients with revision due to hematogenous (acute onset with duration of symptoms 3 months after last surgery) versus non-hematogenous infection • Proportion of patients with unscheduled early revisions (<4 weeks after last scheduled surgical intervention – deep (= bone/joint) revision versus superficial (= skin-soft tissue) revision) • Proportion of patients with aseptic revision • Proportion of patients with implant failure (any functionally affected or pain producing implant, clinically relevant abnormal laboratory test result indicating PJI, or presence of radiological signs of loosening, according to the investigator (Yes/No)). • Proportion of patients with treatment failure (insufficient primary therapy or PJI relapse) • Proportion of patients with initially sufficient versus insufficient primary therapy (defined by the judgement of the investigator, based on combined clinical, laboratory, microbiological and radiological criteria, e.g. clear reduction of wound secretion) • Development and changes vs baseline of specific functional joint scores, and EQ5D5L (in particular for 1 year follow up) • Safety and tolerability of fosfomycin will be evaluated by measuring the frequency of adverse events, including potential side effects • Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Cmax, Tmax, Cmin 8 h, t1/2, AUC0–8, and extrapolated AUC0–24 (in a subpopulation | — |
Countries
Germany
Contacts
Public ContactPrincipal investigator
PRO-IMPLANT Foundation
Outcome results
None listed