Efficacy and Safety of Intravenous Fosfomycin in Prosthetic Joint Infection

NCT05211011 | Unknown Phase 4 DMC

• 1 other identifier: PROOF
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Prosthetic Joint Infection

Outcome Measures

Primary Outcomes (1)

• Infection cure rate

  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.

  1 year

Secondary Outcomes (12)

• Infection cure rate

  2 years

• Proportion of patients with revision

  1 year

• Proportion of patients with revision due to hematogenous versus non-hematogenous infection

  1 year

• Proportion of patients with unscheduled early revisions

  1 year

• Proportion of patients with aseptic revision

  1 year

Study Arms (1)

Fosfomycin Arm

EXPERIMENTAL

Include intravenous fosfomycin in the treatment of PJI according to predetermined algorithm

Drug: Fosfomycin

Interventions

Fosfomycin DRUG

Infectofos 5 g

Also known as: Infectofos

Fosfomycin Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Pro-Implant Foundation: collaborator

Study Sites (16)

BG Universitätsklinikum Bergmannsheil

Bochum, North Rhine-Westphalia, 44789, Germany

Location

Charité

Berlin, 13353, Germany

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Krankenhaus Köln-Merheim

Cologne, 51109, Germany

Location

Städtisches Klinikum Dresden

Dresden, 01067, Germany

Location

Universitätsklinikum Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Waldkrankenhaus Rudolf Elle GmbH

Eisenberg, 07607, Germany

Location

St. Josef Krankenhaus Essen-Werden

Essen, 45239, Germany

Location

Helios Klinikum Hildesheim

Hildesheim, 31135, Germany

Location

Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

St. Franziskus Hospital Münster

Münster, 48145, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Sophien- und Hufelandklinikum GmbH Weimar

Weimar, 99425, Germany

Location

Krankenhaus Johanneum

Wildeshausen, 27793, Germany

Location

Krankenhaus St. Josef

Wuppertal, 42105, Germany

Location

MeSH Terms

Interventions

Fosfomycin

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Study Officials

• Andrej Trampuz, PD Dr

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: In this open prospective interventional clinical study patients with hip, knee or shoulder PJI (as defined below) caused by fosfomycin-susceptible staphylococci, streptococci, enterococci or gram-negative bacilli will be included. After inclusion and PJI-surgery, intravenous fosfomycin will be given 5 g every 8 hours for 1, 2, 3-or -4 weeks according to the pathogen and surgery procedure and generally as a part of the antibiotic combination therapy of the treatment algorithm. This Treatment is followed by oral antibiotics for a total of 3 months.

Study Record Dates

• First Submitted: August 1, 2017
• First Posted: January 27, 2022
• Study Start: January 23, 2018
• Primary Completion: April 30, 2022
• Study Completion: April 30, 2023
• Last Updated: January 27, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (16)