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Status unknownNCT03260010PROOFUpdated Apr 19, 2018

Efficacy and Safety of Intravenous Fosfomycin in Prosthetic Joint Infection

A Phase 4 interventional study of Fosfomycin in Prosthetic Joint Infection, sponsored by Pro-Implant Foundation. Status unknown at 1 site in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-04-19.

Sponsored by Pro-Implant Foundation · Phase 4, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Aug 2017), so the status shown — last known as Recruiting — may be out of date.
Phase
Phase 4
Study type
Interventional
Enrollment
224
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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 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).

02

Conditions studied

  • Prosthetic Joint Infection
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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.

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 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;
  4. Severely compromised bone/soft tissue pre or during surgery (if during surgery: exclusion/withdrawal before IMP application);
  5. Pregnancy, and/or woman 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).
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
224 participants (estimated)

Study arms

  • Experimental
    Fosfomycin Arm

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

    Drug: Fosfomycin

Interventions

  • DrugFosfomycin

    Infectofos 5 g

05

What researchers measure

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.

    Time frame: 1 year

Secondary outcomes

  1. Infection cure rate

    Proportion of patients free of Prosthetic Joint-Infection relapse (infection cure rate) within 2 years after inclusion

    Time frame: 2 years

  2. 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)

    Time frame: 1 year

  3. 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

    Time frame: 1 year

  4. 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)

    Time frame: 1 year

  5. Proportion of patients with aseptic revision

    Proportion of patients with aseptic revision

    Time frame: 1 year

  6. 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))

    Time frame: 1 year

  7. Proportion of patients with treatment failure

    Proportion of patients with treatment failure (insufficient primary therapy or PJI relapse)

    Time frame: 1 year

  8. 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)

    Time frame: 1 year

  9. Specific functional joint scores

    Development and changes vs baseline of specific functional joint scores

    Time frame: 1 year

  10. EQ5D5L

    EQ5D5L (in particular for 1 year follow up)

    Time frame: 1 year

  11. 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

    Time frame: 1 year

  12. Pharmacokinetic profile of fosfomycin in plasma

    Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Cmax

    Time frame: 1 year

  13. Pharmacokinetic profile of fosfomycin in plasma

    Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Tmax

    Time frame: 1 year

  14. Pharmacokinetic profile of fosfomycin in plasma

    Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): Cmin 8 h

    Time frame: 1 year

  15. Pharmacokinetic profile of fosfomycin in plasma

    Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): t1/2

    Time frame: 1 year

  16. Pharmacokinetic profile of fosfomycin in plasma

    Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): AUC0-8

    Time frame: 1 year

  17. Pharmacokinetic profile of fosfomycin in plasma

    Pharmacokinetic profile of fosfomycin in plasma (steady state after a single application per patient): extrapolated AUC0-24

    Time frame: 1 year

06

Study locations

1 of 1 sites recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03260010
Lead sponsor
Pro-Implant Foundation
Collaborators
Charite University, Berlin, Germany
Responsible party
Sponsor
First posted
Aug 24, 2017
Start date
Jan 15, 2018
Primary completion
Apr 15, 2020 (estimated)
Completion
Apr 15, 2021 (estimated)
Last update
Apr 19, 2018

Study contacts

Alessandra Bardelli, MSCPH, MScAC
Contact
alessandra-catalina.bardelli@charite.de
(+49) 030 450 652416
Andrej Trampuz, PD Dr
Contact
andrej.trampuz@charite.de
(+49) 030 450 615073
Andrej Trampuz, PD Dr.
principal investigator · Charité - Univeristätsmedizin

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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