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

Comparison of Two Durations of Antibiotic Therapy in the Treatment of Severe Postoperative Peritonitis Admitted in Intensive Care Unit: a Randomised Multicentre Study

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Peritonitis
• Intervention / Treatment: Other: Duration of antibiotic therapy limited to 8 days

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 Type: Interventional
• Enrollment (Actual): 244
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75018
    • Hôpital Bichat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 8 day-antibiotherapy; 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	Other: Duration of antibiotic therapy limited to 8 days; Initiation of adequate empiric antibiotics for postoperative peritonitis within 24 hours after surgery and up to 8 days. At randomisation performed on day 8, the patients assigned to the 8-day group (short-course group) stop their treatment
No Intervention: 15 day-antibiotherapy; Antibiotics received for up to15 days following surgery for postoperative peritonitis in patients hospitalised in intensive care unit corresponding to usual practice and recommendations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of antibiotic-free days at D28 after inclusion	The number of antibiotic-free days at D28 after inclusion (analysis of superiority)	28 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Philippe Montravers, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: February 22, 2011
• First Submitted That Met QC Criteria: March 8, 2011
• First Posted (Estimate): March 10, 2011

Study Record Updates

• Last Update Posted (Estimate): December 9, 2015
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Surgery; Antibiotic therapy; Laparotomy; Multidrug resistant bacteria; Nosocomial infection; Postoperative peritonitis; Intra-abdominal infection; Duration of treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: P081248