RecruitingPhase 3NCT05148702
EXTENDed Antibiotic Durations Compared to Standard Durations for Patients With Complicated Intra-abdominal Infection.
The EXTEND Trial: Fixed-extended-duration Antibiotics (28 Days) Compared to Standard Care Antibiotic Durations in Adult Patients With Complicated Intra-abdominal Infection and Their Impact on Treatment Failure
Sponsor
Sarah Cockayne
Enrollment
1,166 participants
Start Date
Oct 10, 2022
Study Type
INTERVENTIONAL
Conditions
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.
Eligibility
Min Age: 16 Years
Inclusion Criteria17
- Adults (≥ 16 years) with cIAI* (see cIAI definition)
- Being treated with antibiotics until the point of randomisation, but within 10 days of initiation of effective 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
- In the event that the patient is re-admitted to hospital during the trial period, they are likely to be admitted to a hospital participating in the EXTEND trial.
- 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 neutropaenia (<1.8 x 109 /L) and/or intestinal pathogens cultured from sterile sites (closed peritoneum or blood) around the time of cIAI diagnosis, plus
- Evidence of pathologic findings on radiologic examination, or
- Evidence of pathologic findings at operation
- ** The first day of effective antibiotic treatment will be determined by the patient's clinical team or clinical research team. Antibiotics that do not count towards these 10 days of effective treatment are:
- Antibiotic prophylaxis e.g., penicillin for splenectomy, elective surgery antibiotic prophylaxis, UTI prophylaxis
- Treatment for other infections that is not effective for cIAI e.g., cystitis. Antibiotics that re often used for cystitis and aren't effective for cIAI include Cephalexin, Fosfomycin Trimethoprim, Nitrofurantoin, and Pivmecillinam.
- Oral antibiotics prescribed to treat infection prior to hospitalisation
- Previous courses of treatment antibiotics: A previous course is one stopped for 48 hours or more
- The further 72 hours starts from the first day of effective antibiotic treatment i.e., for a patient admitted to hospital with a cIAI, 3 days of admission are needed. Where a patient is already in hospital e.g., a post operative patient, a further 3 days of admission are required starting from the point of the first day of effective antibiotic treatment.
Exclusion Criteria18
- 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.
- Grade 1 to 3 appendicitis. To be eligible patient must have Grade 4 or 5 appendicitis defined by the 2017 American Association for the Surgery Trauma Grading System with either generalised peritonitis at surgery, or no or partial source control e.g. radiological drainage
- Non-perforated cholecystitis.
- Ischemic or necrotic intestine without perforation
- Uterine perforation following uterine surgery treated <six hours following injury.
- 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. Traumatic injury to the bowel (including iatrogenic or intra-operative) treated within 12 hours of injury, Uterine perforation following uterine surgery treated within six hours of injury, Perforated gastric ulcer or duodenal ulcer treated within 24 hours of the onset of symptoms). 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
- Treatment with Interleukin-6 Inhibitors
- High likelihood of death within 72 hours of cIAI randomisation in the opinion of the local Investigator
- Limitations in treatment decided before inclusion. Limitations in treatment that exclude patients from the EXTEND trial are those clinical decisions linked to an expectation the patient will die during this episode of infection.
- Patient with persistent cIAI of more than 6 months duration
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Interventions
DRUGAntibiotic - standard duration
Clinician decided antibiotic and duration of treatment
DRUGAntibiotic - fixed-extended-duration
Clinician decided antibiotic for a fixed duration of 28 days.
Locations(36)
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NCT05148702