Duration of Antibiotic Therapy in the Treatment of Severe Postoperative Peritonitis Admitted in ICU

Phase 3

Completed

• Conditions: Postoperative Peritonitis
• Interventions: Other: Duration of antibiotic therapy limited to 8 days

• Registration Number: NCT01311765
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2011-02-22
• Study First Submitted QC: 2011-03-08
• Study First Posted: 2011-03-10
• Study Start: 2011-05
• Primary Completion: 2015-03
• Status Verified: 2015-07
• Study Completion: 2015-11
• Last Update Submitted: 2015-12-08
• Last Update Posted: 2015-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 244

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
8 day-antibiotherapy	Duration of antibiotic therapy limited to 8 days	Duration of antibiotic therapy limited to 8 days: Antibiotics received for up to 8 days following surgery for postoperative peritonitis in patients hospitalised in intensive care unit

Primary Outcome Measures

Name	Time	Method
The number of antibiotic-free days at D28 after inclusion	28 days	The number of antibiotic-free days at D28 after inclusion (analysis of superiority)

Secondary Outcome Measures

Name	Time	Method
Number of days alive without organ failure	28 days	Number of days alive without organ failure
Failure rate for clinically evaluable patients	28 days	Failure rate for clinically evaluable patients
Failure rate for microbiologically evaluable patients	28 days	Failure rate for microbiologically evaluable patients
Mortality at D45 after inclusion	45 days	Mortality at D45 after inclusion (analysis of equivalence)
Duration of ICU and hospital stay	45 days	Duration of ICU and hospital stay
Evolution of procalcitonin plasma concentration	15 days	Evolution of procalcitonin plasma concentration
Changes in SOFA score	8 days	Changes in SOFA score
Total cost of antibiotic agents	28 days	Total cost of antibiotic agents
Rate of relapse within 45 days	45 days	Rate of relapse within 45 days
Total cost of hospital stay and evaluation of costs and resources impact for the hospital administration	Hospital discharge	Total cost of hospital stay and evaluation of costs and resources impact for the hospital administration
Emergence of multidrug resistant microorganisms in clinical isolates and hygiene samples	ICU discharge	Emergence of multidrug resistant microorganisms in clinical isolates and hygiene samples
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)	45 days	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)

Trial Locations

Locations (1)

Hôpital Bichat; 🇫🇷 Paris, France