Musculoskeletal InfectionEPHICACINCT06368388
Establishing Personalized Phage Therapy and Its Comparative Cost in Difficult-to-treat Infections (EPHICACI)
An observational study of Musculoskeletal Infection and Chronic Rhinosinusitis (Diagnosis), run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
EPHICACI is a multicenter, prospective study that continues and expands the monocentric PHAGEFORCE registry initiated at UZ Leuven. In Belgium, phage therapy can be applied as standard-of-care only in patients with difficult-to-treat infections where no curative antibiotic and/or surgical alternatives are available… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Musculoskeletal Infection, Chronic Rhinosinusitis (Diagnosis), Persistent Bacteremia
- What is being tested?
- Prospective data collection phage therapy and Prospective data collection standard-of-care
- Type of treatment
- Injection or infusion
- How many people
- 100 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Jun 2021to 31 Dec 2029
- How long will I take part?
- 1 Year
- Phase
- Observational
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All patients: * Diagnosed with an MSI or CRS or persistent bacteremia or or pulmonary infection (cystic fibrosis/bronchiectasis) or HS and * For whom all previous treatments (surgical and antibiotic) have failed or for whom no other treatment options are available (i.e., last resort cases, based on the assessment of the local phage hub), for example in case of bacterial resistance. And * Of whom the pathogen causative for the infection is one for which phages are available in the phage bank, and * Who have given informed consent to have their data collected in a patient registry.
Who may be able to join
- Diagnosed with an MSI or CRS or persistent bacteremia or pulmonary infection (cystic fibrosis/bronchiectasis) or HS and
- For whom all previous treatments (surgical and antibiotic) have failed or for whom no other treatment options are available (i.e., last resort cases, based on the assessment of the local phage hub), for example in case of bacterial resistance. And
- Of whom the pathogen causative for the infection is one for which phages are available in the phage bank, and
- Who have given informed consent to have their data collected in a patient registry
Who cannot join
- All patients:
- With an infectious disease other than those mentioned above, and/or
- For whom standard treatment alternatives are still available. And/or
- Of whom the pathogen causative for the infection is not one for which phages are available in the phage bank. And/or
- Who refused to give their informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
University Hospitals Leuven
Leuven, 3000
Jolien Onsea, PhD, 003216342041, jolien.onsea@uzleuven.be
Willem-Jan Metsemakers, MD, PhD, 003216344277, willem-jan.metsemakers@uzleuven.be
About this study
Official title: Establishing Personalized Phage Therapy and Its Comparative Cost in Difficult-to-treat Infections
EPHICACI is a multicenter, prospective study that continues and expands the monocentric PHAGEFORCE registry initiated at UZ Leuven. In Belgium, phage therapy can be applied as standard-of-care only in patients with difficult-to-treat infections where no curative antibiotic and/or surgical alternatives are available ('last-resort cases'). A multidisciplinary phage task force, the Coordination group for Bacteriophage therapy Leuven (CBL), evaluates eligible patients, tests pathogen susceptibility, and sets up standardized treatment protocols. With EPHICACI, this approach is extended to multiple Belgian expert centers to increase patient enrollment while upholding stringent eligibility criteria. The study aims to gain insight into the safety, efficacy, biodistribution and mechanisms of action of phage therapy, and to optimize its use across five medical disciplines (with distinct routes of administration). In addition, EPHICACI integrates machine learning-based phage-bacteria interaction analyses to guide personalized phage selection, and includes health economic evaluations to support evidence-based implementation and reimbursement strategies.
Read the detailed description
Patients with difficult-to-treat musculoskeletal infections, chronic rhinosinusitis, persistent bacteremia, pulmonary infections associated with cystic fibrosis or bronchiectasis, or hidradenitis suppurativa, for whom no standard (curative) treatment options are available, are eligible for phage therapy. Patient eligibility is assessed by the multidisciplinary Coordination group for Bacteriophage therapy Leuven (CBL), in collaboration with multiple Belgian expert centers. If phages with activity against the isolated bacterial strain are identified and the patient meets all inclusion criteria, a phagogram is performed. Based on these results, patients are either assigned to receive phage therapy or remain in the control group receiving best available non-curative treatment. In both groups, standardized clinical, microbiological and health economic data are collected prospectively using REDCap.
- Conditions
- Musculoskeletal Infection, Chronic Rhinosinusitis (Diagnosis), Persistent Bacteremia, Pulmonary Infection, Hidradenitis Suppurativa
- Being tested
- Prospective data collection phage therapy, Prospective data collection standard-of-care
- Keywords
- Bacteriophage therapy, Personalized treatment, Difficult-to-treat infection, Antimicrobial resistance, Musculoskeletal infections, Chronic rhinosinusitis, Persistent bacteremia, Pulmonary infections, Cystic fibrosis, Bronchiectasis, Hidradenitis suppurativa
- Medical subject headings
- Disease, Hidradenitis Suppurativa, Cystic Fibrosis, Bronchiectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prospective data collection phage therapyOther
Prospective data collection prior to, during and after phage treatment.
Prospective data collection standard-of-careOther
Prospective data collection prior to, during and after standard infection treatment.
| Study group | Role | What they receive |
|---|---|---|
| Phage treated group | Patients whose isolated pathogens are susceptible to the available phages and who have no alternative curative treatment options are included in the phage-treated group. The local phage hub, in consultation with the Phage Consortium, will design the phage therapy treatment plan (local, inhalation, or intravenous) on top of standard surgical and/or antimicrobial care. The treatment plan is documented in the patient's medical file. Patients undergo monitoring according to the phage therapy protocol and follow-up according to standard care for phage-treated patients. Receives: Other: Prospective data collection phage therapy | |
| Control group | Patients whose isolated pathogens are not susceptible to available phages, or for whom phage therapy is not indicated, are included in the control group. These patients receive standard surgical and/or antimicrobial care as determined by the local phage hub. Monitoring and follow-up are according to the standard of care for the underlying pathology. Receives: Other: Prospective data collection standard-of-care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free period
In MSI patients
Measured: Until 1 year after treatment
Smell test
16-point Sniffin' Sticks test in CRS patients
Measured: Until 1 year after treatment
Radiological scores
Lund-Mackay CT score in CRS patients
Measured: Until 1 year after treatment
Endoscopic scores
Lund-Kennedy score and Modified Davos score in CRS patients
Measured: Until 1 year after treatment
Time to clearance of infection
In patients with Persistent Bacteremia
Measured: Until 1 year after treatment, daily during hospitalization until infection clearance
Overall survival
Does the patient survive (for patients with Persistent Bacteremia)
Measured: Until 1 year after treatment
SOFA score
Sequential Organ Failure Assessment (SOFA) score in patients with persistent bacteremia, assessed to monitor changes in organ dysfunction during hospitalization.
Measured: Baseeline and daily during hospitalization until discharge, for up to 12 weeks after cessation of phage therapy; thereafter at 6 months and 1 year after cessation of phage therapy.
Tolerance of the intervention
Proportion of patients with chronic pulmonary infection able to complete the planned phage therapy without treatment discontinuation due to adverse reactions or pulmonary exacerbations.
Measured: During scheduled phage therapy (up to 6 weeks)
Sputum culture conversion assessed by microbiological culture
Proportion of patients with chronic pulmonary infection with conversion from a positive sputum culture for the targeted bacterial pathogen at baseline to a negative sputum culture for the targeted bacterial pathogen after phage therapy.
Measured: Days 1-4 of phage therapy, weekly during phage therapy for up to 6 weeks, and at 6 and 12 months after completion of phage therapy.
Within-subject change in the number of positive cultures
In patients with Chronic Pulmonary Infection
Measured: At 6 and 12 months compared to 12 months prior to therapy
Within-subject change in the number of pulmonary exacerbations requiring additional antibiotic therapy or hospitalization.
In patients with Chronic Pulmonary Infection
Measured: At 6 and 12 months
Clinical response measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).
In patients with Chronic Pulmonary Infection
Measured: Until 1 year after treatment
Improvement in IHS4 score
In HS patients
Measured: Until 1 year after treatment
Improvement in ANF count using HiSCR50 and HiSCR75
In HS patients
Measured: Until 1 year after treatment
Reduction in flare incidence compared to the 12 weeks prior to treatment.
In HS patients
Measured: Until 1 year after treatment
Bacterial load in sinonasal material measured by quantitative microbiological culture
Bacterial load of the targeted bacterial pathogen in sinonasal samples from CRS patients quantified by microbiological culture and expressed as colony-forming units (CFU).
Measured: Until 1 year after treatment
Secondary outcomes (18)
PROMIS global health
specific to MSI, CRS, Chronic Pulmonary Infection
Measured: until 1 year after treatment
PROMIS pain interference
specific to MSI, CRS
Measured: until 1 year after treatment
PROMIS physical function
specific to MSI, CRS
Measured: until 1 year after treatment
iMCQ
specific to MSI, CRS, Persistent bacteremia
Measured: until 1 year after treatment
iPCQ
specific to MSI, CRS, Persistent bacteremia
Measured: until 1 year after treatment
EQ-5D-5L
specific to MSI, CRS, Persistent bacteremia, Chronic Pulmonary Infection, HS
Measured: until 1 year after treatment
SNOT-22
specific to CRS
Measured: until 1 year after treatment
VAS pain
specific to CRS, HS
Measured: until 1 year after treatment
CF-Q
specific to Chronic Pulmonary Infection
Measured: until 1 year after treatment
Bronchiectasis QoL
specific to Chronic Pulmonary Infection
Measured: until 1 year after treatment
FEV1
specific to Chronic Pulmonary Infection
Measured: until 1 year after treatment
FVC
specific to Chronic Pulmonary Infection
Measured: until 1 year after treatment
DLQI
specific to HS
Measured: until 1 year after treatment
HiSQoL
specific to HS
Measured: until 1 year after treatment
Systemic and local phage exposure per route of administration
Specific to MSI, CRS, Chronic pulmonary infection, HS, bacteremia
Measured: until 1 year after treatment
Duration of phage activity in blood or locally
Phage kinetics / pharmacology
Measured: until 1 year after treatment
Change in phage-neutralizing activity measured by serum neutralization test
Phage-neutralizing activity in serum will be assessed using a serum neutralization test (adapted Adams protocol) by measuring the reduction in viable phage titer after incubation with patient serum compared with baseline. Results will be expressed as the log10 reduction in phage titer.
Measured: until 1 year after treatment
Change in bacterial load of the targeted pathogen measured by quantitative microbiological culture
Change in bacterial load of the targeted bacterial pathogen in clinical samples collected during and after phage therapy, quantified by microbiological culture and expressed as CFU per mL.
Measured: until 1 year after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2024
- Study start1 Jun 2021
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Musculoskeletal InfectionStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven, University Hospital, Antwerp, University Ghent, Universitair Ziekenhuis Brussel, AZ Sint-Jan AV, Queen Astrid Military Hospital, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, Clinique Saint Pierre Ottignies, Sciensano
- Responsible party
- Sponsor
- Investigators
- Willem-Jan Metsemakers, MD, PhD, Principal investigator, UZ / KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06368388
- Sponsor's protocol ID
- S64854
- Acronym
- EPHICACI
- Status last verified
- Aug 2026
- First submitted
- 4 Apr 2024
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Onsea J, Uyttebroek S, Chen B, Wagemans J, Lood C, Van Gerven L, Spriet I, Devolder D, Debaveye Y, Depypere M, Dupont L, De Munter P, Peetermans WE, van Noort V, Merabishvili M, Pirnay JP, Lavigne R, Metsemakers WJ. Bacteriophage Therapy for Difficult-to-Treat Infections: The Implementation of a Multidisciplinary Phage Task Force (The PHAGEFORCE Study Protocol). Viruses. 2021 Aug 5;13(8):1543. doi: 10.3390/v13081543.
PubMed 34452408