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NCT Number: NCT06368388

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

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.

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Key information

Conditions

Musculoskeletal Infection Bacterial Infections Bacterial Infections and Mycoses Bronchial Diseases Bronchiectasis Chronic Rhinosinusitis (Diagnosis) Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cystic Fibrosis Digestive System Diseases Disease Genetic Diseases, Inborn Hidradenitis Hidradenitis Suppurativa Infant, Newborn, Diseases Infections Lung Diseases Pancreatic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Persistent Bacteremia Pulmonary Infection Respiratory Tract Diseases Skin Diseases Skin Diseases, Bacterial Skin Diseases, Infectious Skin and Connective Tissue Diseases Suppuration Sweat Gland Diseases

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

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

Treatment and study plan

Prospective data collection phage therapy

Other

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

Prospective data collection standard-of-care

Other

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

Primary outcomes

  1. Disease-free period

    Time frame: Until 1 year after treatment

    In MSI patients

  2. Smell test

    Time frame: Until 1 year after treatment

    16-point Sniffin' Sticks test in CRS patients

  3. Radiological scores

    Time frame: Until 1 year after treatment

    Lund-Mackay CT score in CRS patients

  4. Endoscopic scores

    Time frame: Until 1 year after treatment

    Lund-Kennedy score and Modified Davos score in CRS patients

  5. Time to clearance of infection

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

    In patients with Persistent Bacteremia

  6. Overall survival

    Time frame: Until 1 year after treatment

    Does the patient survive (for patients with Persistent Bacteremia)

  7. SOFA score

    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.

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

  8. Tolerance of the intervention

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

    Proportion of patients with chronic pulmonary infection able to complete the planned phage therapy without treatment discontinuation due to adverse reactions or pulmonary exacerbations.

  9. Sputum culture conversion assessed by microbiological culture

    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.

    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.

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

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

    In patients with Chronic Pulmonary Infection

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

    Time frame: At 6 and 12 months

    In patients with Chronic Pulmonary Infection

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

    Time frame: Until 1 year after treatment

    In patients with Chronic Pulmonary Infection

  13. Improvement in IHS4 score

    Time frame: Until 1 year after treatment

    In HS patients

  14. Improvement in ANF count using HiSCR50 and HiSCR75

    Time frame: Until 1 year after treatment

    In HS patients

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

    Time frame: Until 1 year after treatment

    In HS patients

  16. Bacterial load in sinonasal material measured by quantitative microbiological culture

    Time frame: Until 1 year after treatment

    Bacterial load of the targeted bacterial pathogen in sinonasal samples from CRS patients quantified by microbiological culture and expressed as colony-forming units (CFU).

Secondary outcomes

  1. PROMIS global health

    Time frame: until 1 year after treatment

    specific to MSI, CRS, Chronic Pulmonary Infection

  2. PROMIS pain interference

    Time frame: until 1 year after treatment

    specific to MSI, CRS

  3. PROMIS physical function

    Time frame: until 1 year after treatment

    specific to MSI, CRS

  4. iMCQ

    Time frame: until 1 year after treatment

    specific to MSI, CRS, Persistent bacteremia

  5. iPCQ

    Time frame: until 1 year after treatment

    specific to MSI, CRS, Persistent bacteremia

  6. EQ-5D-5L

    Time frame: until 1 year after treatment

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

  7. SNOT-22

    Time frame: until 1 year after treatment

    specific to CRS

  8. VAS pain

    Time frame: until 1 year after treatment

    specific to CRS, HS

  9. CF-Q

    Time frame: until 1 year after treatment

    specific to Chronic Pulmonary Infection

  10. Bronchiectasis QoL

    Time frame: until 1 year after treatment

    specific to Chronic Pulmonary Infection

  11. FEV1

    Time frame: until 1 year after treatment

    specific to Chronic Pulmonary Infection

  12. FVC

    Time frame: until 1 year after treatment

    specific to Chronic Pulmonary Infection

  13. DLQI

    Time frame: until 1 year after treatment

    specific to HS

  14. HiSQoL

    Time frame: until 1 year after treatment

    specific to HS

  15. Systemic and local phage exposure per route of administration

    Time frame: until 1 year after treatment

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

  16. Duration of phage activity in blood or locally

    Time frame: until 1 year after treatment

    Phage kinetics / pharmacology

  17. Change in phage-neutralizing activity measured by serum neutralization test

    Time frame: until 1 year after treatment

    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.

  18. Change in bacterial load of the targeted pathogen measured by quantitative microbiological culture

    Time frame: until 1 year after treatment

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Jolien Onsea, PhD

CONTACT

[email protected]

00321642041

Willem-Jan Metsemakers, MD, PhD

CONTACT

[email protected]

003216344277

Sponsors and collaborators

Lead sponsor

Universitaire Ziekenhuizen KU Leuven

Other

Collaborators

  • AZ Sint-Jan AV
  • Clinique Saint Pierre Ottignies
  • Cliniques universitaires Saint-Luc- Université Catholique de Louvain
  • KU Leuven
  • Queen Astrid Military Hospital
  • Sciensano
  • Universitair Ziekenhuis Brussel
  • University Ghent
  • University Hospital, Antwerp

Registry information

Official study title

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

Acronym: EPHICACI

Important dates

Study start
2021
Primary completion
2028
Study completion
2029
First posted
Apr 16, 2024
Registry last updated
Sep 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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