Clinical trial NCT01311765: Duration of Antibiotic Therapy in the Treatment of Severe Postoperative Peritonitis Admitted in ICU
Official title: Comparison of Two Durations of Antibiotic Therapy in the Treatment of Severe Postoperative Peritonitis Admitted in Intensive Care Unit: a Randomised Multicentre Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Peritonitis
Keywords: Postoperative peritonitis
Intra-abdominal infection
Surgery
Laparotomy
Nosocomial infection
Antibiotic therapy
Duration of treatment
Multidrug resistant bacteria
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2011-03-10
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators purpose is to demonstrate that a short antibiotic therapy (8 days) for postoperative peritonitis brings an increased number of antibiotic-free days over a 28 days period when compared to conventional (15 days) treatment.

Detailed description: This is a prospective randomized study involving 25 centers. Our goal is to demonstrate in the course of postoperative peritonitis that a short antibiotic therapy (8 days) compared to conventional antibiotic treatment (15 days) decreases the duration of exposure to antibiotics over a 28 days period . Patients admitted in ICU, operated for postoperative peritonitis and receiving an adequate antibiotic therapy will be identified and after informed consent is obtained will be randomized to receive a short course of antibiotic therapy (8 days) or a long course of antibiotic therapy (15 days). The primary endpoint is the number of antibiotic-free days at D28 after inclusion (analysis of superiority) . Secondary endpoints include mortality at D45 after inclusion (analysis of equivalence), the occurrence of relapse of infection, success rate of clinically and microbiologically evaluable patients, and emergence of multidrug resistant microorganisms in clinical isolates or hygiene samples. Patient data through day 45 following the initial intervention or until hospital discharge will be tracked.

Eligibility criteria: Inclusion Criteria:

The eligible patients have to fulfill all the following criteria

1. patients admitted in intensive care unit
2. in the 24 hours following surgery for postoperative intra-abdominal infection (defined as gross pus or purulent effusion within the peritoneal cavity or in one or several collections). Postoperative infection will be defined as an infection observed in a delay of 60 days following a procedure (endoscopy, surgery (abdominal, urologic, gynecologic or vascular surgery or any surgery performed in the peritoneal or retroperitoneal space) or interventional radiology)
3. having peroperative microbiologic samples collected
4. receiving an empiric antibiotic therapy initiated within the first 24 hours after completion of surgery
5. with a written informed consent from the patient or the relative or the legal representative or with an emergency consent

Non-inclusion criteria :

Patients with one of the following criteria are eligible for the study :

1. age\<18
2. pregnancy
3. Duration of stay following inclusion \<72 hours
4. neutropenia (PMN\<500/mm3) due to chemotherapy or hematological disease
5. AIDS stage C
6. Immunosuppressive therapy or prolonged steroid therapy (≥0.5 mg/kg/d of prednisone or equivalent \>1 month
7. Bowel perforation following endoscopy treated in a delay \<6 hours after injury
8. Uterine perforation following a surgical procedure treated in a delay \<6 hours after injury
9. Moribund patient (SAPS II score \>65 within 12 hours preceding inclusion)
10. Limitation of treatment previously decided
11. Surgery considered as non curative by the surgeon
12. Patient included in another clinical trial evaluating an antimicrobial agent

Secondary exclusion criteria:

Among the eligible patients, those who have one of the following criteria will be excluded

1. Negative culture of the peritoneal fluid
2. Peritoneal culture exclusively fungal
3. Inadequate empiric antibiotic therapy (not targeting all the microorganisms cultured from peritoneal or blood cultures) within 24 hours after surgery
4. Death between D1 and D8

Primary outcomes:
measure: The number of antibiotic-free days at D28 after inclusion
timeFrame: 28 days
Secondary outcomes:
measure: Mortality at D45 after inclusion
timeFrame: 45 days
measure: Duration of ICU and hospital stay
timeFrame: 45 days
measure: Changes in SOFA score
timeFrame: 8 days
measure: Number of days alive without organ failure
timeFrame: 28 days
measure: Failure rate for clinically evaluable patients
timeFrame: 28 days
measure: Failure rate for microbiologically evaluable patients
timeFrame: 28 days
measure: Rate of relapse within 45 days
timeFrame: 45 days
measure: Emergence of multidrug resistant microorganisms in clinical isolates and hygiene samples
timeFrame: ICU discharge
measure: Total cost of antibiotic agents
timeFrame: 28 days
measure: Evolution of procalcitonin plasma concentration
timeFrame: 15 days
measure: Rate of death within 45 days in specific subpopulations (elderly patients >80 years ; morbidly obese patients BMI>25kg/m2 ; severe infection with SAPSII score >40 ;peritoneal infection involving pseudomonas or enterococci ; bacteriemic infections)
timeFrame: 45 days
measure: Total cost of hospital stay and evaluation of costs and resources impact for the hospital administration
timeFrame: Hospital discharge
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Bichat
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Philippe Montravers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Montravers P, Tubach F, Lescot T, Veber B, Esposito-Farese M, Seguin P, Paugam C, Lepape A, Meistelman C, Cousson J, Tesniere A, Plantefeve G, Blasco G, Asehnoune K, Jaber S, Lasocki S, Dupont H; DURAPOP Trial Group. Short-course antibiotic therapy for critically ill patients treated for postoperative intra-abdominal infection: the DURAPOP randomised clinical trial. Intensive Care Med. 2018 Mar;44(3):300-310. doi: 10.1007/s00134-018-5088-x. Epub 2018 Feb 26.