Comparison of the Efficacy of Standard Treatment Associated With Phage Therapy Versus Standard Treatment Plus Placebo for Diabetic Foot Ulcers Monoinfected by Staphylococcus Aureus: a Randomized, Multi-centre, Controlled, 2-parallel-group, Double-blind, Superiority Trial

Centre Hospitalier Universitaire de Nīmes6 sites in 1 country60 target enrollmentSeptember 1, 2026

ConditionsDiabetic Foot Staphylococcal Infections

InterventionsTopical anti-Staphylococcus bacteriophage therapy Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy

DrugsTopical anti-Staphylococcus bacteriophage therapy Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy

Overview

Phase: Phase 1
Intervention: Topical anti-Staphylococcus bacteriophage therapy
Conditions: Diabetic Foot
Sponsor: Centre Hospitalier Universitaire de Nīmes
Enrollment: 60
Locations: 6
Primary Endpoint: The relative reduction in wound surface area (%)
Status: Not yet recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of this study is to compare the efficacy of standard treatment associated with a topical anti-staphylococcal bacteriophage cocktail versus standard treatment plus placebo for diabetic foot ulcers monoinfected by methicillin-resistant or susceptible S. aureus (MRSA or MSSA) as measured by the relative reduction in wound surface area (%) at 12 weeks.

Detailed Description

The secondary objectives of this study are: A. To compare the two study arms in terms of treatment safety and tolerance throughout the study. B. To compare the two study arms in terms of further changes in wound healing at weeks 2, 4, 6, 8, 10, 12. C. To describe the changes in the resistance and virulence of S. aureus (if present in the wound) from baseline to week 4, at modification of the first-line treatment or new antibiotic prescription (if any) and at week 12 if the wound is still not healed. D. To describe in the two study arms the antibiotic resistance status of other bacteria isolated from wounds at week 4, at modification of the first-line treatment or new antibiotic prescription (if any) and at week 12 if the wound is still not healed. E. To describe in the two study arms changes in wound microbiota from baseline to week 4, at modification of the first-line treatment or new antibiotic prescription (if any) and at week 12 if the wound is still not healed. F. To describe the production of anti-phage antibodies during the topical treatment: baseline and week 4, at modification of the first-line treatment or new antibiotic prescription (if any), and at week 12. G. Creation of a biobank for future ancillary studies (including, but not limited to, cytokine levels and cellular immune responses): days 0 and week 4, as well as week 12.

Registry

clinicaltrials.gov

Start Date

September 1, 2026

End Date

November 1, 2028

Last Updated

last month

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Centre Hospitalier Universitaire de Nīmes

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participant pre-inclusion criteria:
•The patient must have given his/her informed and signed consent
•The patient must be insured or beneficiary of a health insurance plan
•The patient is at least 18 years old
•The patient has type 1 or type 2 diabetes
•The patient is hospitalized/consulting in a participating centre
•The patient has a wound below the ankle that has be evolving for \>2 weeks
•The patient has a neuropathic foot wound, classified S (0 or 1), I (0 or 1), N (1), B (1), A (0 or1) and D (1) according to the SINBAD classification,
•without ischaemia or with non-critical ischaemia defined by: ankle arterial pressure \> 50 mm Hg or toe systolic arterial pressure \> 30 mm Hg or TcpO2 \> 30 mm Hg )
•with a surface area ≥ 0,5 cm2

Exclusion Criteria

•The patient is participating in, or has participated in over the past three months, another trial
•The patient is participating in, or has participated in over the past three months, another study that may interfere with the results or conclusions of this study
•The patient is in an exclusion period determined by a previous study
•The patient is under judicial protection, or is an adult under guardianship
•It is impossible to correctly inform the patient
•The patient refuses to sign the consent
•The patient is pregnant, parturient or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period and 1 month after the last administration of study drug
•Women/Men refusing to use an effective contraception during and1 month after the last administration of study drug
•Participant final exclusion criteria:
•The patient refuses to participate to the study

Arms & Interventions

Phage therapy

Patients randomized to this arm will have phage therapy. Intervention: Topical anti-Staphylococcus bacteriophage therapy

Intervention: Topical anti-Staphylococcus bacteriophage therapy

Placebo

Patients randomized to this arm will have placebo therapy anologous to that of the experimental arm. Intervention: Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy

Intervention: Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy

Outcomes

Primary Outcomes

The relative reduction in wound surface area (%)

Time Frame: 12 weeks

Secondary Outcomes

Wound surface area(12 weeks)
Wound microbiota: OTU richness(at week 12 if the wound is still not healed)
Immediate Safety(Day 14, 1 hour after application of experimental dressing)
Time to healing(censored at 12 weeks)
The number of MedDRA coded Adverse Events per patient(throughout the study; 12 weeks)
The presence/absence of abnormal laboratory results(throughout the study; 12 weeks)
Wound depth(12 weeks)
The % of completely healed wounds(12 weeks)
Classification of Staphylococcus isolates according to clonal complexes (virulence classification)(at week 12 if the wound is still not healed)
Presence/absence of non-Staphylococcus aureus bacteria that are antibiotic-resistant(at week 12 if the wound is still not healed)
Wound microbiota: Functional richness(at week 12 if the wound is still not healed)
Classification of Staphylococcus isolates as MSSA or MRSA resistant(at week 12 if the wound is still not healed)
Wound microbiota: the number of Staphylococcus strains in a wound(at week 12 if the wound is still not healed)
Wound microbiota: Shannon's Diversity(at week 12 if the wound is still not healed)
Wound microbiota: Functional diversity(at week 12 if the wound is still not healed)
The presence/absence of anti-phage antibodies in plasma samples(at week 12 if the wound is still not healed)
Wound microbiota: the relative abundance of Staphylococcus relative to other bacteria in the wound(at week 12 if the wound is still not healed)
Wound microbiota: ordination scores on each of two principal components extracted from UniFrac distances between all bacterial samples taken during the study(at week 12 if the wound is still not healed)
Wound microbiota: the relative abundance of Staphylococcus aureus relative to other bacteria in the wound(at week 12 if the wound is still not healed)
Wound microbiota: the relative abundance of Staphylococcus aureus relative to other Staphylococcus in the wound(at week 12 if the wound is still not healed)
Wound surface area(8 weeks)
Wound surface area(10 weeks)
Wound depth(2 weeks)
Wound depth(4 weeks)
Wound depth(6 weeks)
Wound depth(8 weeks)
Wound depth(10 weeks)
Wound microbiota: Functional richness(week 0)
Immediate Safety(Day 0, 1 hour after application of experimental dressing)
Immediate Safety(Day 7, 1 hour after application of experimental dressing)
Wound surface area(2 weeks)
Wound surface area(4 weeks)
Wound surface area(6 weeks)
Classification of Staphylococcus isolates as MSSA or MRSA resistant(4 weeks)
Classification of Staphylococcus isolates as MSSA or MRSA resistant(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Classification of Staphylococcus isolates according to clonal complexes (virulence classification)(4 weeks)
Classification of Staphylococcus isolates according to clonal complexes (virulence classification)(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Presence/absence of non-Staphylococcus aureus bacteria that are antibiotic-resistant(week 0)
Presence/absence of non-Staphylococcus aureus bacteria that are antibiotic-resistant(week 4)
Presence/absence of non-Staphylococcus aureus bacteria that are antibiotic-resistant(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Wound microbiota: OTU richness(week 0)
Wound microbiota: OTU richness(week 4)
Wound microbiota: OTU richness(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Wound microbiota: Shannon's Diversity(week 0)
Wound microbiota: Shannon's Diversity(week 4)
Wound microbiota: Shannon's Diversity(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Wound microbiota: Functional richness(week 4)
Wound microbiota: Functional richness(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Wound microbiota: Functional diversity(week 0)
Wound microbiota: Functional diversity(week 4)
Wound microbiota: Functional diversity(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Wound microbiota: the relative abundance of Staphylococcus relative to other bacteria in the wound(week 0)
Wound microbiota: the relative abundance of Staphylococcus relative to other bacteria in the wound(week 4)
Wound microbiota: the relative abundance of Staphylococcus relative to other bacteria in the wound(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Wound microbiota: the number of Staphylococcus strains in a wound(week 0)
Wound microbiota: the number of Staphylococcus strains in a wound(week 4)
Wound microbiota: the number of Staphylococcus strains in a wound(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Wound microbiota: the relative abundance of Staphylococcus aureus relative to other bacteria in the wound(week 0)
Wound microbiota: the relative abundance of Staphylococcus aureus relative to other bacteria in the wound(week 4)
Wound microbiota: the relative abundance of Staphylococcus aureus relative to other bacteria in the wound(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Wound microbiota: the relative abundance of Staphylococcus aureus relative to other Staphylococcus in the wound(week 0)
Wound microbiota: the relative abundance of Staphylococcus aureus relative to other Staphylococcus in the wound(week 4)
Wound microbiota: the relative abundance of Staphylococcus aureus relative to other Staphylococcus in the wound(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
Wound microbiota: ordination scores on each of two principal components extracted from UniFrac distances between all bacterial samples taken during the study(week 0)
Wound microbiota: ordination scores on each of two principal components extracted from UniFrac distances between all bacterial samples taken during the study(week 4)
Wound microbiota: ordination scores on each of two principal components extracted from UniFrac distances between all bacterial samples taken during the study(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))
The presence/absence of anti-phage antibodies in plasma samples(week 0)
The presence/absence of anti-phage antibodies in plasma samples(week 4)
The presence/absence of anti-phage antibodies in plasma samples(at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks))