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

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.

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.

Study Overview

• Status: Unknown
• Conditions: Wound Infection
• Intervention / Treatment: Drug: Standard of care : Silver Sulfadiazine; Drug: E. coli Phages cocktail; Drug: P. Aeruginosa, Phages cocktail

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, B-1120
    • Not yet recruiting
    • Hopital Militaire Reine Astrid
    • Principal Investigator: Serge Jennes, MD
    • Contact: Jean-Paul Pirnay, PhD; Phone Number: +32 2 264 4844; Email: jean-paul.pirnay@mil.be
  • Liege, Belgium
    • Not yet recruiting
    • CHU Sart-Tilman
    • Contact: Anne-Françoise Rousseau, MD; Phone Number: +32 4 3667495; Email: afrousseau@chu.ulg.ac.be
    • Principal Investigator: Anne-Françoise Rousseau, MD
• France
  • Clamart, France, 92141
    • Recruiting
    • Hôpital d'Instruction des Armées PERCY
    • Contact: Patrick Jault, MD; Phone Number: +33 (0)1 41 46 62 13; Email: patrick.jault@santarm.fr
    • Contact: Thomas Leclerc, MD; Phone Number: +33 (0)1 41 46 62 13; Email: thomas.leclerc@m4x.org
    • Principal Investigator: Patrick Jault, MD
    • Sub-Investigator: Thomas Leclerc, MD
  • Lyon, France, F-69365
    • Not yet recruiting
    • Centre hospitalier ST Joseph et St Luc
    • Contact: François Ravat, MD; Phone Number: +33 (0) 478 618 925; Email: fravat@ch-stjoseph-stluc-lyon.fr
    • Principal Investigator: François Ravat, MD
• Switzerland
  • Lausanne, Switzerland, CH-1011
    • Not yet recruiting
    • Centre Hospitalier Universitaire Vaudois
    • Contact: Grégory Resch, PhD; Phone Number: +41 21 692 56 23; Email: gregory.resch@unil.ch
    • Principal Investigator: Yok-Ai Que, Mer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Pherecydes Pharma
• Investigators: Principal Investigator: Patrick Jault, MD, Service de Santé des Armées, Hopital Percy (Clamart, France)

Publications and helpful links

General Publications

• Jault P, Leclerc T, Jennes S, Pirnay JP, Que YA, Resch G, Rousseau AF, Ravat F, Carsin H, Le Floch R, Schaal JV, Soler C, Fevre C, Arnaud I, Bretaudeau L, Gabard J. Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial. Lancet Infect Dis. 2019 Jan;19(1):35-45. doi: 10.1016/S1473-3099(18)30482-1. Epub 2018 Oct 3.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): July 1, 2016

Study Registration Dates

• First Submitted: April 1, 2014
• First Submitted That Met QC Criteria: April 14, 2014
• First Posted (Estimate): April 16, 2014

Study Record Updates

• Last Update Posted (Estimate): July 24, 2015
• Last Update Submitted That Met QC Criteria: July 23, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Wound Infection in burned patient
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Infections; Communicable Diseases; Wounds and Injuries; Wound Infection; Escherichia coli Infections; Anti-Infective Agents, Local; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Coccidiostats; Sulfadiazine; Silver Sulfadiazine
• Other Study ID Numbers: PHAGOBURN