Evaluation of Phage Therapy for the Treatment of Escherichia Coli and Pseudomonas Aeruginosa Wound Infections in Burned Patients

Study Overview
=================
Brief Summary
-----------------
The objective of PHAGOBURN is to assess tolerance and efficacy of local bacteriophage treatment of E. coli or P. aeruginosa wound infections in burned patients.

Detailed Description
-----------------
PHAGOBURN is a Phase I/II clinical trial randomized, multicentric, open label, standard of care (Silver Sulfadiazine) controlled aiming at assessing tolerance and efficacy of local bacteriophage treatment of wound infections due to E. coli or P. aeruginosa in burned patients using Pherecydes Pharma anti-Escherichia coli and anti-Pseudomonas aeruginosa bacteriophage cocktails GMP produced. This project is a European Research & Development (R&D) project funded by the European Commission under the 7th Framework Programme for Research and Development. This project is involving 7 clinical sites in EU.

Official Title
-----------------
Phase I/II Clinical Trial Randomized, Multicentric, Open Label, Standard of Care (Silver Sulfadiazine) Controlled Aiming at Assessing Tolerance and Efficacy of Local Bacteriophage Treatment of Wound Infections Due to E. Coli or P. Aeruginosa in Burned Patients Using Pherecydes Pharma Anti-Escherichia Coli and Anti-Pseudomonas Aeruginosa Bacteriophages GMP Produced Cocktails . This Project is a European Research & Development (R&D) Project Funded by the European Commission Under the 7th Framework Programme for Research and Development Involving 7 Clinical Sites in EU.

Conditions
-----------------
Wound Infection

Intervention / Treatment
-----------------
* Drug: E. coli Phages cocktail
* Drug: Standard of care : Silver Sulfadiazine
* Drug: P. Aeruginosa, Phages cocktail


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Man or woman Adult Informed consent obtained from patient or next of kin In-hospital patient treated for burn wounds in a burn unit Burn wound (grafted or not) or graft harvesting area, presenting local signs of infection defined by SFETB criteria: A local or loco-regional inflammatory reaction; And/or an adverse and unexpected local evolution; And/or regarding burn wounds: presence of pus, fast spontaneous debridement and separation, occurrence of blackish spots (necrosis or haemorrhage), unexplained conversion from a superficial lesion to a deep one (> 48th hour); And/or regarding graft donor sites: presence of pus, unexplained delay in epidermisation, bedsore; And/or regarding graft recipient sites: presence of pus, lysis of grafts, necrosis of fat located under the graft. Burn wounds with a microbiologically documented infection, as defined by positive surface swab, due to Escherichia coli or Pseudomonas aeruginosa whatever their resistance profile Treated by povidone-iodine Exclusion Criteria: Pregnant or breastfeeding woman Intercurrent condition requiring a treatment which may interfere with analysis results: such as high dose of chronic corticotherapy, immunosuppressive medication, oncologic chemotherapy Patient included in an interventional research protocol with therapeutic intervention still ongoing upon inclusion time or having participated into anti-infective drug trials during the previous month. Patient considered as part of a vulnerable population Patient for whom treatment limitation or withdrawal during study period is considered Allergy to Silver Sulfadiazine

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: E. coli, Standard of care : Silver Sulfadiazine<br>Burn wounds infected by E. coli treated with Standard of care : Silver Sulfadiazine | Drug: Standard of care : Silver Sulfadiazine<br>* Use of Standard of care : Silver Sulfadiazine, to treat E. coli or P. aeruginosa infected burn wound<br>|
| Experimental: E. coli, Phages cocktail<br>Burn wounds infected by E. coli treated with Pherecydes Pharma Phages cocktail | Drug: E. coli Phages cocktail<br>* Use of Pherecydes Pharma Phages cocktail to treat respectively E. coli burn wound infection<br>|
| Active Comparator: P. aeruginosa, Standard of care : Silver Sulfadiazine<br>Burn wounds infected with P. aeruginosa treated with Standard of care : Silver Sulfadiazine | Drug: Standard of care : Silver Sulfadiazine<br>* Use of Standard of care : Silver Sulfadiazine, to treat E. coli or P. aeruginosa infected burn wound<br>|
| Experimental: P. aeruginosa, Phages cocktail<br>Burn wounds infected by P. aeruginosa treated treated with Pherecydes Pharma Phages cocktail | Drug: P. Aeruginosa, Phages cocktail<br>* Use of Pherecydes Pharma Phages cocktail to treat P. aeruginosa burn wound infection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time for bacteria reduction adjusted on antibiotic treatment | Time necessary for a persistent bacteria reduction of two modes or persistent bacteria eradication relative to D0 adjusted on antibiotic treatment (active on targeted strain) introduced between D1 to D7. Bacteria count performed on bacteria targeted by the phages cocktail collected from surface swab samples assessed by the microbiologist. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of tolerance of treatment | Adverse events frequencies will be assessed in each treatment arms. Phages therapy safety profile will be compared to safety profile of standard of care . | 21 days | 
| Incidence an delay of infection reduction with different bacterial species from the targets | The criteria will be assessed according to wound clinical examination and bacteria count by the microbiologist. | 7 days | 
| number of sites cured | The number of infected burns or infected wounds getting a clinical improvement will be described and compared between treatment groups. | 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Wound Infection in burned patient