EXTENDed Antibiotic Durations Compared to Standard Durations for Patients With Complicated Intra-abdominal Infection.

• Status: Not yet recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

A multicentre, open label, two-arm, parallel group, pragmatic, randomised controlled trial with internal pilot. A total of 1166 consenting adult patients with cIAI will be recruited and randomised on a 1:1 basis between 28-days antibiotics and standard care antibiotics. Patients will be followed up for 180 days to determine cost effectiveness and the rate of treatment failure in each group.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of York
• Collaborator: University of Leeds
• Treatments: Anti-Bacterial Agents; Antibiotics, Antitubercular

Criteria

Inclusion Criteria:

• Adults (≥ 18 years) with cIAI (see cIAI definition)

• Being treated with antibiotics until the point of randomisation, but within 10 days of initiation of antibiotic treatment for cIAI

• Ability to provide informed consent by the patient or their consultee.

• More than 72 hours of active in-patient management for the patients cIAI is required Specific inclusions where patients require more than 72 hours of in-patient management, are

• Patients with diverticulitis abscess

• Perforated appendix with peri-appendiceal phlegmon, abscess or diffuse peritonitis (Grade 5 and 6 of the 2017 American Association for the Surgery on Trauma Grading System)

• Discrete pancreatic infections (abscess, infected pseudocyst)

• Patients will be included in the trial whether or not they undergo surgical or radiological source control procedures.

• cIAI is defined by the following case definition:

• A clinical presentation consistent with cIAI, plus

• Fever (temperature of ≥ 37.8°C) and/or a neutrophilia (> 7.5×109/L) and/or pathogens cultured from sterile sites (closed peritoneum or blood) with an intestinal pathogen, plus

• Evidence of pathologic findings on radiologic examination, or

• Evidence of pathologic findings at operation

Exclusion Criteria:

• Perforated gastric ulcer or duodenal ulcer treated within 24 hours of the onset of symptoms.

• Traumatic injury to the bowel (including iatrogenic or intra-operative) treated within 12 hours of injury.

• Uncomplicated diverticulitis defined as an episode with a short history and with clinical signs of diverticulitis, with an increased body temperature and inflammatory parameters, verified by computed tomography (CT), and without any sign of complications such as abscess, free air or fistula.

• Non-perforated, non-gangrenous appendicitis (Grade 4 and below of the 2017 American Association for the Surgery on Trauma Grading System) or cholecystitis.

• Ischemic or necrotic intestine without perforation

• Uterine perforation following uterine surgery treated- cIAIs with a low risk of complications who may receive more than 72 hours antibiotics are not intended to be included, such as those listed above. Clinician assessment on the eligibility of patients receiving more than 72 hours of in-patient surgical care and antibiotics for their cIAI may be required in patients who have clinically improved at this point and do not require active surgical care but remain in hospital and on antibiotics.

• Current enrolment in another trial dictating antibiotic treatment duration.

• Previous Clostridium difficile infection

• Infected necrotic pancreatitis

• Concomitant infection requiring ≥4 weeks antibiotic therapy including Intra-hepatic abscess/es planned to be treated with fixed-extended-duration antibiotics of 4 to 6 weeks antibiotics, osteomyelitis, and endocarditis.

• Peritoneal dialysis

• Previously recruited for the EXTEND trial

• cIAI with an antimicrobially resistant infection without a safe (non-toxic) and effective antibiotic treatment option

• Treatment with Interleukin-6 Inhibitors

• High likelihood of death within 72 hours of cIAI randomisation in the opinion of the local Investigator or limitations in treatment decided before inclusion

• Patient with persistent cIAI of more than 6 months duration

• Specific non-exclusions are;

• Placement of drains and irrigation of the abdomen do not exclude patients from the trial.

• Immunodeficiency/Steroids/Pregnancy/Malignancy do not exclude patients from the trial.

• Patients with anastomotic leak will not be excluded from the trial.

• Patients with infected Central Venous Catheters.

• Prolonged use of central venous catheter prophylaxis e.g., Tauralock

• Patients on long term antibiotics for prophylaxis of recurrent urinary tract infection or splenectomy.

• Patients with a relapse of a cIAI not previously recruited for the EXTEND trial. Patients who relapse should have not received antibiotic treatment for their cIAI in the preceding two weeks.

• A maximum of 20% of participants entering the trial can have a source of cIAI as the appendix. If 230 patients with appendix as the source are recruited, this will become an exclusion criteria for subsequent patients.