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

NCT06368388 | Recruiting DMC

• 1 other identifier: S64854
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Persistent Bacteremia; Musculoskeletal Infection; Chronic Rhinosinusitis (Diagnosis); 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

Outcome Measures

Primary Outcomes (16)

• Disease-free period

  In MSI patients

  Until 1 year after treatment

• Smell test

  16-point Sniffin' Sticks test in CRS patients

  Until 1 year after treatment

• Radiological scores

  Lund-Mackay CT score in CRS patients

  Until 1 year after treatment

• Endoscopic scores

  Lund-Kennedy score and Modified Davos score in CRS patients

  Until 1 year after treatment

• Time to clearance of infection

  In patients with Persistent Bacteremia

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

• Overall survival

  Does the patient survive (for patients with Persistent Bacteremia)

  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.

  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.

  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.

  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

  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

  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

  Until 1 year after treatment

• Improvement in IHS4 score

  In HS patients

  Until 1 year after treatment

• Improvement in ANF count using HiSCR50 and HiSCR75

  In HS patients

  Until 1 year after treatment

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

  In HS patients

  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).

  Until 1 year after treatment

Secondary Outcomes (18)

• PROMIS global health

  until 1 year after treatment

• PROMIS pain interference

  until 1 year after treatment

• PROMIS physical function

  until 1 year after treatment

• iMCQ

  until 1 year after treatment

• iPCQ

  until 1 year after treatment

Study Arms (2)

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

Prospective data collection phage therapy OTHER

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

Phage treated group

Prospective data collection standard-of-care OTHER

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

Control group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

University Hospitals Leuven

Leuven, 3000, Belgium

RECRUITING

Related Publications (1)

• 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.

  PMID: 34452408 BACKGROUND

MeSH Terms

Conditions

Disease; Hidradenitis Suppurativa; Cystic Fibrosis; Bronchiectasis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Diseases, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Infectious; Suppuration; Skin Diseases; Skin and Connective Tissue Diseases; Hidradenitis; Sweat Gland Diseases; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Bronchial Diseases

Study Officials

• Willem-Jan Metsemakers, MD, PhD

  UZ / KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jolien Onsea, PhD

CONTACT

00321642041; jolien.onsea@uzleuven.be

Willem-Jan Metsemakers, MD, PhD

CONTACT

003216344277; willem-jan.metsemakers@uzleuven.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2024
• First Posted: April 16, 2024
• Study Start: June 1, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: September 21, 2026

Record last verified: 2026-08

Locations

BE (1)