Prosthetic Joint InfectionPhase 4PROOFNCT03260010
Efficacy and Safety of Intravenous Fosfomycin in Prosthetic Joint Infection
A Phase 4 study testing Fosfomycin in people with Prosthetic Joint Infection, run by Pro-Implant Foundation at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prosthetic Joint Infection
- What is being tested?
- Fosfomycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 1 siteGermany
- Study dates
- 15 Jan 2018to 15 Apr 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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).
Trial locations and contacts
1 site in 1 country.
Alessandra Bardelli, MSCPH, MScAC contact
Germany1 site, 1 recruiting
- Recruiting
Charité - Univeristätsmedizin
Berlin, 13353
Svetlana Karbysheva, +49 30 450 615 048, svetlana.karbysheva@charite.de
About this study
Official title: 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.
Read the 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).
- Conditions
- Prosthetic Joint Infection
- Being tested
- Fosfomycin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FosfomycinDrug
Infectofos 5 g
| Study group | Role | What they receive |
|---|---|---|
| Fosfomycin Arm | Experimental | Include intravenous fosfomycin in the treatment of PJI according to predetermined algorithm Receives: Drug: Fosfomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (17)
Infection cure rate
Proportion of patients free of Prosthetic Joint-Infection relapse (infection cure rate) within 2 years after inclusion
Measured: 2 years
Proportion of patients with revision
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)
Measured: 1 year
Proportion of patients with revision due to hematogenous versus non-hematogenous infection
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
Measured: 1 year
Proportion of patients with unscheduled early revisions
Proportion of patients with unscheduled early revisions (<4 weeks after last scheduled surgical intervention - deep (= bone/joint) revision versus superficial (= skin-soft tissue) revision)
Measured: 1 year
Proportion of patients with aseptic revision
Proportion of patients with aseptic revision
Measured: 1 year
Proportion of patients with implant failure
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))
Measured: 1 year
Proportion of patients with treatment failure
Proportion of patients with treatment failure (insufficient primary therapy or PJI relapse)
Measured: 1 year
Proportion of patients with initially sufficient versus insufficient primary therapy
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)
Measured: 1 year
Specific functional joint scores
Development and changes vs baseline of specific functional joint scores
Measured: 1 year
EQ5D5L
EQ5D5L (in particular for 1 year follow up)
Measured: 1 year
Safety and tolerability of fosfomycin (frequency of adverse events)
Safety and tolerability of fosfomycin will be evaluated by measuring the frequency of adverse events, including potential side effects
Measured: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Cmax
Measured: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Tmax
Measured: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Cmin 8 h
Measured: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): t1/2
Measured: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): AUC0-8
Measured: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): extrapolated AUC0-24
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2017
- Study start15 Jan 2018
- Primary completion15 Apr 2020 (estimated)
- Study completion15 Apr 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prosthetic Joint InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 224 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pro-Implant Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Charite University, Berlin, Germany
- Responsible party
- Sponsor
- Investigators
- Andrej Trampuz, PD Dr., Principal investigator, Charité - Univeristätsmedizin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03260010
- Sponsor's protocol ID
- PROOF
- Acronym
- PROOF
- Status last verified
- Aug 2017
- First submitted
- 15 Aug 2017
- Last updated
- 19 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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")
- ClinicalTrials.gov ID
- NCT03260010
- Acronym / sponsor ID
- PROOF / PROOF
- Conditions
- Prosthetic Joint Infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 224 participants (estimated)
- Lead sponsor
- Pro-Implant FoundationUniversity, hospital or other
- Collaborators
- Charite University, Berlin, Germany
- Study start
- 15 Jan 2018 (actual)
- Primary completion
- 15 Apr 2020 (estimated)
- Study completion
- 15 Apr 2021 (estimated)
- First posted
- 24 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Fosfomycin Arm | Experimental | Drug: FosfomycinInclude intravenous fosfomycin in the treatment of PJI according to predetermined algorithm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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);
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FosfomycinInfectofos 5 g | Drug | Fosfomycin Arm |
Primary outcome
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.
17 secondary outcomes
Infection cure rate
Time frame: 2 years
Proportion of patients with revision
Time frame: 1 year
Proportion of patients with revision due to hematogenous versus non-hematogenous infection
Time frame: 1 year
Proportion of patients with unscheduled early revisions
Time frame: 1 year
Proportion of patients with aseptic revision
Time frame: 1 year
Proportion of patients with implant failure
Time frame: 1 year
Proportion of patients with treatment failure
Time frame: 1 year
Proportion of patients with initially sufficient versus insufficient primary therapy
Time frame: 1 year
Specific functional joint scores
Time frame: 1 year
EQ5D5L
Time frame: 1 year
Safety and tolerability of fosfomycin (frequency of adverse events)
Time frame: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Time frame: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Time frame: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Time frame: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Time frame: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Time frame: 1 year
Pharmacokinetic profile of fosfomycin in plasma
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alessandra Bardelli, MSCPH, MScAC contact
Andrej Trampuz, PD Dr. principal investigator
Charité - Univeristätsmedizin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fosfomycin in people with Prosthetic Joint Infection, run by Pro-Implant Foundation at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alessandra Bardelli, MSCPH, MScAC ((+49) 030 450 652416, alessandra-catalina.bardelli@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infection cure rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2018.