Bacteriophage Therapy for Difficult-to-treat Infections: the Implementation of a Multidisciplinary Phage Task Force (PHAGEFORCE)

PHAGEFORCE is a prospective, observational registry study. The University Hospitals Leuven has approved the application of phage therapy as standard-of-care only in patients for whom no curative treatment alternatives (antibiotic and/or surgical) are available ('last-resort cases'). A multidisciplinary phage task force, referred to as the Coordination group for Bacteriophage therapy Leuven (CBL) was set up. The CBL screens patients with difficult-to-treat infections, evaluates who could benefit from phage therapy and sets up the treatment protocol. With this study, the CBL aims to gain insight in the safety and efficacy of phage therapy by integrating and optimizing phage therapy in five distinct medical disciplines (with distinct routes of administration), facilitating long-term follow-up of patients. Furthermore, this study will gain insight in the biodistribution and exact mechanisms of action of phage therapy and thus be able to provide standardized guidelines for each patient population and route of administration.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Chronic Rhinosinusitis (Diagnosis); Hidradenitis Suppurativa; Pulmonary Infection; Musculoskeletal Infection
• Intervention / Treatment: Other: Prospective data collection; Other: Prospective data collection

Detailed Description

Patients with difficult-to-treat musculoskeletal infections, chronic rhinosinusitis, sepsis, 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 evaluated by the Coordination group for Bacteriophage therapy Leuven. If phages are available against the isolated bacterial species and the patient is found eligible for phage therapy, a phagogram is performed. Solely based on the results of the phagogram, the patient is either included in the phage treated or control group (standard (non-curative) treatment). In both cases, data is collected using REDCap.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Jolien Onsea, PhD; Phone Number: 00321642041; Email: jolien.onsea@uzleuven.be
• Study Contact Backup: Name: Willem-Jan Metsemakers, MD, PhD; Phone Number: 003216344277; Email: willem-jan.metsemakers@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospitals Leuven
    • Contact: Willem-Jan Metsemakers, MD, PhD; Phone Number: 003216344277; Email: willem-jan.metsemakers@uzleuven.be
    • Contact: Jolien Onsea, PhD; Phone Number: 003216342041; Email: jolien.onsea@uzleuven.be
    • Principal Investigator: Willem-Jan Metsemakers, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All patients with a musculoskeletal infection or sepsis or chronic rhinosinusitis or pulmonary infection (associated with bronchiectasis or cystic fibrosis) or hidradenitis suppurativa for whom all previous treatments (anti-inflammatory/antibiotic/surgical) have failed or are likely to fail, or for whom no other treatments are available (i.e. in case of antibiotic resistance).

Description

Inclusion Criteria:

All patients:

• Diagnosed with a musculoskeletal infection or chronic rhinosinusitis or sepsis or lung infection (CF/Bx) or hidradenitis suppurativa, 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 CBL), 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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Phage treated group; Solely depending on the susceptibility of the isolates against the available phages (phagogram) the CBL will decide if the patient can be included in the phage treated group or the control group. Patients in the phage treated group will receive phage therapy according to the medical indication (local for musculoskeletal infections, hidradenitis suppurativa and CRS, through inhalation for pulmonary infections, intravenous for sepsis) on top of (surgical/antimicrobial) standard treatment.	Other: Prospective data collection; Prospective data collection prior to, during and after phage treatment.; Other: Prospective data collection; Prospective data collection prior to, during and after standard infection treatment.
Control group; Patients for whom the isolated pathogens are not susceptible to the available phages are included in the control group. These patients receive standard (non-curative) surgical/antimicrobial treatment.	Other: Prospective data collection; Prospective data collection prior to, during and after phage treatment.; Other: Prospective data collection; Prospective data collection prior to, during and after standard infection treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free period		1 year after treatment
Bacterial eradication	specific to sepsis patients, evaluated by negative hemocultures	3 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS global health (patient-reported outcome measurement information system)	specific to musculoskeletal infections, chronic rhinosinusitis and pulmonary infections; higher scores mean better outcome	until 1 year after treatment
PROMIS (patient-reported outcome measurement information system) physical function	specific to musculoskeletal infections (higher scores mean better outcome)	until 1 year after treatment
PROMIS (patient-reported outcome measurement information system) pain interference	specific to musculoskeletal infections (higher scores mean worse outcome)	until 1 year after treatment
Sino-nasal outcome test (SNOT)-22	specific to chronic rhinosinusitis, lower scores mean a better outcome	until 1 year after treatment
Visual Analogue Scale (VAS) score	specific to chronic rhinosinusitis and hidradenitis suppurativa, higher scores mean more pain	until 1 year after treatment
Cystic fibrosis questionnaire (CF-Q-R)	specific to pulmonary infections, higher scores mean better quality of life	until 1 year after treatment
Dermatology Life Quality Index (DLQI)	specific to hidradenitis suppurativa, higher scores mean worse outcome (impaired quality of life)	until 1 year after treatment
Hidradenitis Suppurativa Quality of Life (HiSQoL)	specific to hidradenitis suppurativa, higher scores indicate a higher level of symptomatology (worse outcomes)	until 1 year after treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of exacerbations	specific to pulmonary infections	until 12 months after treatment
Abscess and inflammatory nodule (AN) count with Hidradenitis suppurativa Clinical Response (HiSCR)	specific to hidradenitis suppurativa. At least a 50% reduction from baseline in the total AN count, with no increase from baseline in abscess or draining tunnel count	until 3 months after treatment
Lund-Mackay CT score	specific to chronic rhinosinusitis, higher scores mean more occlusion	until 3 months after treatment
Lund Kennedy endoscopy score	specific to chronic rhinosinusitis, higher scores mean more occlusion	until 3 months after treatment
Modified Davos score	specific to chronic rhinosinusitis, higher scores mean more occlusion	until 3 months after treatment

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: April 4, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Bacteriophage therapy; Personalized treatment; Difficult-to-treat infection
• Additional Relevant MeSH Terms: Pathologic Processes; Sweat Gland Diseases; Skin Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Disease Attributes; Otorhinolaryngologic Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Paranasal Sinus Diseases; Nose Diseases; Suppuration; Skin Diseases, Bacterial; Rhinitis; Sinusitis; Infections; Communicable Diseases; Hidradenitis Suppurativa; Hidradenitis; Rhinosinusitis
• Other Study ID Numbers: S64854

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No