- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03260010
Efficacy and Safety of Intravenous Fosfomycin in Prosthetic Joint Infection (PROOF)
April 17, 2018 updated by: Pro-Implant Foundation
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")
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.
Study Overview
Detailed Description
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).
Study Type
Interventional
Enrollment (Anticipated)
224
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Alessandra Bardelli, MSCPH, MScAC
- Phone Number: (+49) 030 450 652416
- Email: alessandra-catalina.bardelli@charite.de
Study Contact Backup
- Name: Andrej Trampuz, PD Dr
- Phone Number: (+49) 030 450 615073
- Email: andrej.trampuz@charite.de
Study Locations
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-
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Berlin, Germany, 13353
- Recruiting
- Charité - Univeristätsmedizin
-
Contact:
- Svetlana Karbysheva
- Phone Number: +49 30 450 615 048
- Email: svetlana.karbysheva@charite.de
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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/withdrawal before 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 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);
- 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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Fosfomycin Arm
Include intravenous fosfomycin in the treatment of PJI according to predetermined algorithm
|
Infectofos 5 g
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Infection cure rate
Time Frame: 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.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Infection cure rate
Time Frame: 2 years
|
Proportion of patients free of Prosthetic Joint-Infection relapse (infection cure rate) within 2 years after inclusion
|
2 years
|
Proportion of patients with revision
Time Frame: 1 year
|
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)
|
1 year
|
Proportion of patients with revision due to hematogenous versus non-hematogenous infection
Time Frame: 1 year
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Proportion of patients with revision due to hematogenous (acute onset with duration of symptoms <3 weeks and onset of symptoms is >3 months after last surgery) versus non-hematogenous infection
|
1 year
|
Proportion of patients with unscheduled early revisions
Time Frame: 1 year
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Proportion of patients with unscheduled early revisions (<4 weeks after last scheduled surgical intervention - deep (= bone/joint) revision versus superficial (= skin-soft tissue) revision)
|
1 year
|
Proportion of patients with aseptic revision
Time Frame: 1 year
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Proportion of patients with aseptic revision
|
1 year
|
Proportion of patients with implant failure
Time Frame: 1 year
|
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))
|
1 year
|
Proportion of patients with treatment failure
Time Frame: 1 year
|
Proportion of patients with treatment failure (insufficient primary therapy or PJI relapse)
|
1 year
|
Proportion of patients with initially sufficient versus insufficient primary therapy
Time Frame: 1 year
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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)
|
1 year
|
Specific functional joint scores
Time Frame: 1 year
|
Development and changes vs baseline of specific functional joint scores
|
1 year
|
EQ5D5L
Time Frame: 1 year
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EQ5D5L (in particular for 1 year follow up)
|
1 year
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Safety and tolerability of fosfomycin (frequency of adverse events)
Time Frame: 1 year
|
Safety and tolerability of fosfomycin will be evaluated by measuring the frequency of adverse events, including potential side effects
|
1 year
|
Pharmacokinetic profile of fosfomycin in plasma
Time Frame: 1 year
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Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Cmax
|
1 year
|
Pharmacokinetic profile of fosfomycin in plasma
Time Frame: 1 year
|
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Tmax
|
1 year
|
Pharmacokinetic profile of fosfomycin in plasma
Time Frame: 1 year
|
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Cmin 8 h
|
1 year
|
Pharmacokinetic profile of fosfomycin in plasma
Time Frame: 1 year
|
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): t1/2
|
1 year
|
Pharmacokinetic profile of fosfomycin in plasma
Time Frame: 1 year
|
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): AUC0-8
|
1 year
|
Pharmacokinetic profile of fosfomycin in plasma
Time Frame: 1 year
|
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): extrapolated AUC0-24
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Andrej Trampuz, PD Dr., Charité - Univeristätsmedizin
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 15, 2018
Primary Completion (Anticipated)
April 15, 2020
Study Completion (Anticipated)
April 15, 2021
Study Registration Dates
First Submitted
August 15, 2017
First Submitted That Met QC Criteria
August 21, 2017
First Posted (Actual)
August 24, 2017
Study Record Updates
Last Update Posted (Actual)
April 19, 2018
Last Update Submitted That Met QC Criteria
April 17, 2018
Last Verified
August 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PROOF
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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