Clinical trial NCT04292054: Antibioprophylaxis for Excision-graft Surgery in Burn Patient (A2B-TRIAL)
Official title: "Antibioprophylaxis for Excision-graft Surgery in Burn Patient: a Multicenter Randomized Double-blind Study: A2B Trial"
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Burns Surgery
Keywords: Antibioprophylaxis
sepsis
infection
graft lysis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-03-02
Enrollment: 506
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized controlled study with two arms (1:1)

Arm 1 : With antibiotic prophylaxis strategy, (cefazolin) if absence of colonization to Pseudomonas aeruginosa; or (piperacilline-tazobactam) if the burn is colonized with Pseudomonas aeruginosa.

Arm 2 : Without antibiotic prophylaxis strategy (placebo)
Primary purpose: TREATMENT

Brief summary: The indication of antibiotic prophylaxis in burn patients remains highly controversial and hasn't reached a consensus. The objective of antibiotic prophylaxis would be to reduce the risk of post-operative local and systemic infections. Burn surgery is associated with a high risk of bacteremia and postoperative infections and sepsis. However, antibiotic prophylaxis exposes to the risk of selecting drug-resistant pathogens as well as adverse effects of antibiotics (i.e Clostridium difficile colitis).

Recommendations regarding perioperative prophylaxis using systemic antibiotics vary across sources. The lack of data precludes any international strong recommendations regarding the best strategy regarding antibiotic prophylaxis.

The goal of this project is therefore to determine whether peri-operative systemic antibiotics prophylaxis could reduce the incidence of post-operative infections in burn patients.

Detailed description: The intensive care unit investigator will verify the inclusion and non-inclusion criteria.

The following parameters will be collected at ICU/burn centers: Hemodynamic parameters; sepsis organ failure assessment (SOFA) score, Glasgow Coma scale; Medical history / comorbidities; Concomitant treatment; Burn wound bacterial colonization; Biological parameters.

The inclusion and randomization will be performed as late as possible before the first surgical procedure.

Randomization: Burn patients with deep burn between 5 to 40% TBSA requiring at least one excision surgery graft will be randomized to receive antibioprophylaxis (or placebo) 30 minutes before the incision with either first generation cephalosporin (cefazolin) (if absence of colonization to Pseudomonas aeruginosa); or piperacillin-tazobactam (if the burned area is colonized with Pseudomonas aeruginosa). We chose to target specifically Pseudomonas aeruginosa because it has been associated with significant morbidity and risk of graft lysis in burn patients.

No specific exams are required during the 7 days, 28 days and 90 days follow up visits.

The end of research visit is the 90-day follow-up visit. If the patient has been discharged from the hospital, the 90-day visit will consist of a telephone contact with the patient if he or she has been discharged home or with the medical team of the healthcare structure if the patient has been discharged to another structure.

Eligibility criteria: Inclusion Criteria:

* Patient over 18 years and less than 80 years old
* Burned patients requiring at least one excision-graft surgery
* Burn TBSA% between 5% and 40%
* Signed informed consent or inclusion under the emergency provisions of the law (article L1122-1-2 of the CSP)

Exclusion Criteria:

* Proven severe allergy to cephalosporin or piperacilline-tazobactam or any other antibacterial agent of the penicillin class
* History of severe allergic reaction to any other beta-lactam (eg cephalosporins, monobactams or carbapenems)
* Patient on antibiotic therapy at the time of inclusion
* Pregnant or breast-feeding patient
* Patient not covered by the social security
* Patient transferred from another burn Unit
* Patient participant in investigational competitive medicinal product study on the primary endpoint
* Patient with local or systemic signs of infection requiring systemic antimicrobial therapy
* Patient under guardian ship
* Patient under curatorship
* Known colonization of the burned area to be excised with tazocillin-resistant germ.
* Obese patient

Primary outcomes:
measure: Post-operative infection defined as Post-operative sepsis and/or Surgical site infection, and/or Graft lysis requiring a new graft within 7 days after surgery.
timeFrame: 7 days after surgery
measure: Post-operative sepsis
timeFrame: 7 days after surgery
measure: Surgical site infection
timeFrame: 7 days after surgery
measure: Graft lysis needing a new graft procedure
timeFrame: 7 days after surgery
Secondary outcomes:
measure: Mortality
timeFrame: At day 90
measure: Skin graft lysis requiring a new graft procedure
timeFrame: 7 days after surgery
measure: Postoperative bacteremia
timeFrame: within 7 days of surgery
measure: Post-operative pulmonary infection
timeFrame: 7 days after surgery
measure: Post-operative surgical site infection
timeFrame: 7 days after surgery
measure: Number of hospitalization days living without antibiotic therapy
timeFrame: at Day 28 and Day 90
measure: Number of days of hospitalization until complete healing (> 95% total burn surface area)
timeFrame: at Day 28 and Day 90
measure: Number of patients with a colonization with a multidrug resistant bacteria.
timeFrame: at Day 28 and Day 90
Other outcomes:
Locations:
city: Paris
country: France
facility: Saint Louis Hospital
Study officials:
affiliation: Department of Anesthesiology, Critical Care and Burn Unit; Saint-Louis hospital
name: François DEPRET, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Depret F, Farny B, Jeanne M, Klouche K, Leclerc T, Nouette-Gaulain K, Pantet O, Remerand F, Roquilly A, Rousseau AF, Sztajnic S, Wiramus S, Vicaut E, Legrand M; A2B trial investigators. The A2B trial, antibiotic prophylaxis for excision-graft surgery in burn patients: a multicenter randomized double-blind study. Trials. 2020 Nov 25;21(1):973. doi: 10.1186/s13063-020-04894-y.