Standard Treatment Associated With Phage Therapy Versus Placebo for Diabetic Foot Ulcers Infected by S. Aureus
- Conditions
- Staphylococcal InfectionsDiabetic Foot
- Interventions
- Drug: Topical placebo corresponding to anti-Staphylococcus bacteriophage therapyDrug: Topical anti-Staphylococcus bacteriophage therapy
- Registration Number
- NCT02664740
- Lead Sponsor
- Centre Hospitalier Universitaire de NÄ«mes
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy 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 Phage therapy Topical anti-Staphylococcus bacteriophage therapy Patients randomized to this arm will have phage therapy. Intervention: Topical anti-Staphylococcus bacteriophage therapy
- Primary Outcome Measures
Name Time Method The relative reduction in wound surface area (%) 12 weeks
- Secondary Outcome Measures
Name Time Method Wound depth 12 weeks Wound surface area 12 weeks Immediate Safety Day 14, 1 hour after application of experimental dressing The presence/absence of the following symptoms during each 1 hour observation periods following the application of each experimental wound dressing: local side effects (local rash onset or worsening of local inflammatory signs) and general symptoms (vital signs, fever, rash, arthralgia, gastro-intestinal symptoms...) will be performed.
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 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 MSSA: Methicillin-susceptible Staphylococcus aureus MRSA: Methicillin-resistant Staphylococcus aureus
What is reported is a binary result: isolates are classified as either "MSSA" or "MRSA"Wound microbiota: OTU richness at week 12 if the wound is still not healed OTU: Operational Taxonomic Unit
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
Trial Locations
- Locations (9)
APHP - Hôpital Lariboisière
🇫🇷Paris, France
CHRU de Nîmes - Hôpital Universitaire de Réadaptation du Grau du Roi
🇫🇷Le Grau du Roi, France
APHP - Groupe Hospitalier Pitié-Salpetrière
🇫🇷Paris Cedex 13, France
CHU de Bordeaux - Hôpital Pellegrin
🇫🇷Bordeaux, France
CHU de Nantes - Hôtel Dieu
🇫🇷Nantes Cedex 1, France
CH de Tourcoing
🇫🇷Tourcoing, France
CHRU de Toulouse - Hôpital de Rangueil
🇫🇷Toulouse Cedex 9, France
CH Intercommunal de Villeneuve-Saint-Georges
🇫🇷Villeneuve-Saint-Georges, France
Institut Robert Merle d'Aubigné
🇫🇷Valenton, France