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

Universitaire Ziekenhuizen KU Leuven100 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

100

Conditions

Musculoskeletal Infection

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Disease-free period

In MSI patients

Time frame: Until 1 year after treatment

Smell test

16-point Sniffin' Sticks test in CRS patients

Time frame: Until 1 year after treatment

Radiological scores

Lund-Mackay CT score in CRS patients

Time frame: Until 1 year after treatment

Endoscopic scores

Lund-Kennedy score and Modified Davos score in CRS patients

Time frame: Until 1 year after treatment

Time to clearance of infection

In patients with Persistent Bacteremia

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

Overall survival

Does the patient survive (for patients with Persistent Bacteremia)

Time frame: 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.

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.

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)

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.

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

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

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

Improvement in IHS4 score

In HS patients

Time frame: Until 1 year after treatment

Improvement in ANF count using HiSCR50 and HiSCR75

In HS patients

Time frame: Until 1 year after treatment

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

In HS patients

Time frame: 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).

Time frame: Until 1 year after treatment