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RecruitingNCT06368388EPHICACIUpdated Sep 21, 2026

Establishing Personalized Phage Therapy and Its Comparative Cost in Difficult-to-treat Infections (EPHICACI)

An observational study in Musculoskeletal Infection, Chronic Rhinosinusitis (Diagnosis) and Persistent Bacteremia, sponsored by Universitaire Ziekenhuizen KU Leuven. Recruiting at 1 site in Belgium. Per ClinicalTrials.gov, last updated 2026-09-21.

Sponsored by Universitaire Ziekenhuizen KU Leuven · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
100
Sex
All
01

Study 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 ('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.

02

Conditions studied

  • Musculoskeletal Infection
  • Chronic Rhinosinusitis (Diagnosis)
  • Persistent Bacteremia
  • Pulmonary Infection
  • Hidradenitis Suppurativa

Keywords

  • Bacteriophage therapy
  • Personalized treatment
  • Difficult-to-treat infection
  • Antimicrobial resistance
  • Musculoskeletal infections
  • Chronic rhinosinusitis
  • Persistent bacteremia
  • Pulmonary infections
  • Cystic fibrosis
  • Bronchiectasis
  • Hidradenitis suppurativa
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

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.

Inclusion criteria

  • 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

Exclusion criteria

Exclusion Criteria:

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
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
100 participants (estimated)
Target follow-up
1 Year
Patient registry
Yes

Groups and cohorts

  • 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.

    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.

    Other: Prospective data collection standard-of-care

Interventions

  • OtherProspective data collection phage therapy

    Prospective data collection prior to, during and after phage treatment.

  • OtherProspective data collection standard-of-care

    Prospective data collection prior to, during and after standard infection treatment.

05

What researchers measure

Primary outcomes

  1. Disease-free period

    In MSI patients

    Time frame: Until 1 year after treatment

  2. Smell test

    16-point Sniffin' Sticks test in CRS patients

    Time frame: Until 1 year after treatment

  3. Radiological scores

    Lund-Mackay CT score in CRS patients

    Time frame: Until 1 year after treatment

  4. Endoscopic scores

    Lund-Kennedy score and Modified Davos score in CRS patients

    Time frame: Until 1 year after treatment

  5. Time to clearance of infection

    In patients with Persistent Bacteremia

    Time frame: Until 1 year after treatment, daily during hospitalization until infection clearance

  6. Overall survival

    Does the patient survive (for patients with Persistent Bacteremia)

    Time frame: Until 1 year after treatment

  7. SOFA score

    Sequential Organ Failure Assessment (SOFA) score in patients with persistent bacteremia, assessed to monitor changes in organ dysfunction during hospitalization.

    Time frame: 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.

  8. 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.

    Time frame: During scheduled phage therapy (up to 6 weeks)

  9. 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.

    Time frame: 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.

  10. Within-subject change in the number of positive cultures

    In patients with Chronic Pulmonary Infection

    Time frame: At 6 and 12 months compared to 12 months prior to therapy

  11. Within-subject change in the number of pulmonary exacerbations requiring additional antibiotic therapy or hospitalization.

    In patients with Chronic Pulmonary Infection

    Time frame: At 6 and 12 months

  12. Clinical response measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).

    In patients with Chronic Pulmonary Infection

    Time frame: Until 1 year after treatment

  13. Improvement in IHS4 score

    In HS patients

    Time frame: Until 1 year after treatment

  14. Improvement in ANF count using HiSCR50 and HiSCR75

    In HS patients

    Time frame: Until 1 year after treatment

  15. Reduction in flare incidence compared to the 12 weeks prior to treatment.

    In HS patients

    Time frame: Until 1 year after treatment

  16. 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).

    Time frame: Until 1 year after treatment

Secondary outcomes

  1. PROMIS global health

    specific to MSI, CRS, Chronic Pulmonary Infection

    Time frame: until 1 year after treatment

  2. PROMIS pain interference

    specific to MSI, CRS

    Time frame: until 1 year after treatment

  3. PROMIS physical function

    specific to MSI, CRS

    Time frame: until 1 year after treatment

  4. iMCQ

    specific to MSI, CRS, Persistent bacteremia

    Time frame: until 1 year after treatment

  5. iPCQ

    specific to MSI, CRS, Persistent bacteremia

    Time frame: until 1 year after treatment

  6. EQ-5D-5L

    specific to MSI, CRS, Persistent bacteremia, Chronic Pulmonary Infection, HS

    Time frame: until 1 year after treatment

  7. SNOT-22

    specific to CRS

    Time frame: until 1 year after treatment

  8. VAS pain

    specific to CRS, HS

    Time frame: until 1 year after treatment

  9. CF-Q

    specific to Chronic Pulmonary Infection

    Time frame: until 1 year after treatment

  10. Bronchiectasis QoL

    specific to Chronic Pulmonary Infection

    Time frame: until 1 year after treatment

  11. FEV1

    specific to Chronic Pulmonary Infection

    Time frame: until 1 year after treatment

  12. FVC

    specific to Chronic Pulmonary Infection

    Time frame: until 1 year after treatment

  13. DLQI

    specific to HS

    Time frame: until 1 year after treatment

  14. HiSQoL

    specific to HS

    Time frame: until 1 year after treatment

  15. Systemic and local phage exposure per route of administration

    Specific to MSI, CRS, Chronic pulmonary infection, HS, bacteremia

    Time frame: until 1 year after treatment

  16. Duration of phage activity in blood or locally

    Phage kinetics / pharmacology

    Time frame: until 1 year after treatment

  17. 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.

    Time frame: until 1 year after treatment

  18. 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.

    Time frame: until 1 year after treatment

06

Study locations

1 of 1 sites recruiting
07

References and documents

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 ↗
08

Registry details

Key details

Study ID
NCT06368388
Lead sponsor
Universitaire Ziekenhuizen KU Leuven
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
First posted
Apr 16, 2024
Start date
Jun 1, 2021
Primary completion
Dec 31, 2028 (estimated)
Completion
Dec 31, 2029 (estimated)
Last update
Sep 21, 2026

Study contacts

Jolien Onsea, PhD
Contact
jolien.onsea@uzleuven.be
00321642041
Willem-Jan Metsemakers, MD, PhD
Contact
willem-jan.metsemakers@uzleuven.be
003216344277
Willem-Jan Metsemakers, MD, PhD
principal investigator · UZ / KU Leuven

Oversight

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

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