Evaluation of phage therapy for the treatment of Pseudomonas aeruginosa wound infections in burned patients (Phase I-II clinical trial)

Phase 1

Conditions: P. aeruginosa infected wound in burned patients.
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2014-000714-65-BE

Lead Sponsor: Pherecydes Pharma SA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 125

Inclusion Criteria

Man or woman 18 years old or more
Informed consent obtained from patient or next of kin
In-hospital patient treated for burn wounds in a burn unit
Burn wounds with a microbiologically documented infection defined by positive surface swab, due to P. aeruginosa whatever their resistance profile.
As poly-microbial infections are usual in burn wounds infection, when one another bacterial specie is also present on the wound, the patient may be included whether this specie is rare and overwhelmed by the targeted strain (daily swabs will support monitoring the burden of the colonizing specie)
Patients with local infection due to P. aeruginosa without general signs.
Patients with local infection due to P. aeruginosa and general signs, and without antibiotic treatment.
Patients with local infection due to P. aeruginosa and general signs, and with active or non-active antibiotic treatment at the inclusion (randomization and stratification).
Patients with local infection due to P. aeruginosa and general signs, and with non-active antibiotic treatment during the protocol.
Patients with local infection due to P. aeruginosa and general signs, and treated with active antibiotic treatment during the protocol must be considered as failure of local treatment.
Burn wound (grafted or not) or donor site, presenting local signs of infection defined by one or more of the following 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 hemorrhage), 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, bed sore;
- And/or regarding graft recipient sites: presence of pus, lysis of grafts, necrosis of fat located under the graft.
Patient treated by povidone-iodine, or any dressing without silver for more than one day before inclusion

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Pregnant or breastfeeding woman
Undercurrent condition requiring a treatment which may interfere with analysis results: such as high dose of chronic corticotherapy, immunosuppressive medication, oncologic chemotherapy (but antibiotic treatment is not an exclusion criterion, see below).
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 with a secondary colonization by another species than P. aeruginosa if the colonization level is growing to infection
Patient considered as part of a vulnerable population as defined by the ICH.
Patient for whom treatment limitation or withdrawal during study period is considered.
Patient with general or local sensitization to Sulphonamide (contact dermatitis)
Patients previously included in this study.
Patients who have experienced an increase in the SOFA score greater than or equal to 2 during the 48 hours preceding the inclusion day.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of PHAGOBURN study is to assess the efficacy and safety of topical applications of PP1131 bacteriophage cocktail, targeting P. aeruginosa infected third degree wounds in hospitalized patients, in comparison to silver sulfadiazine treatment.;Secondary Objective: •Assessment of tolerance of treatment<br>•Incidence and delay of infection with different bacterial species from the targets<br>•Incidence and timing of severe sepsis or septic shock attributable to E coli or P aeruginosa<br>•Reasons for patient’s withdrawal from study (tolerance, graft …)<br>•Number of sites cured<br>;Primary end point(s): Time necessary for a persistent bacteria reduction of two modes (technique of the quarters ) or persistent bacteria eradication relative to D0 adjusted on antibiotic treatment (active on targeted strain) introduced between D1 to D7 ;Timepoint(s) of evaluation of this end point: Efficacy evaluation performed every day between inclusion and Day 7, then at Day 14.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Same as primary endpoint without adjustment on antibiotic treatment<br>•Rate of bacteria reduction<br>•Time and rate of improvement or disappearance of clinical signs according to criteria defined by the SFETB guidelines<br>•P. aeruginosa Time to bacteria reduction global rate (bacteriological count diminution of 2 modes relative to D0 bacteria count following technique of the quarters), to be evaluated every day from inclusion date to end of trial and at Day 7.<br>•Timing and indication of systemic antibiotic treatment (active on targeted strain)<br>•Incidence and delay of infection with bacterial species different from the one targeted <br>•Incidence and timing of severe sepsis or septic shock attributable to targeted skin infection<br>•Reasons for patient’s withdrawal from study (tolerance, graft …)<br>•Number of sites cured<br>;Timepoint(s) of evaluation of this end point: Day 0 to 7, D14 and Day 21