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

NCT05148702 | Recruiting Phase 3 DMC

• 2 other identifiers: NIHR131784ISRCTN 72819021
• Study Type: interventional
• Target: 1,166
• Locations: 1 country
• Sites: 36

Brief 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.

Conditions

Complicated Intra-abdominal Infection

Keywords

infection; antibiotics; antibiotic resistance

Outcome Measures

Primary Outcomes (1)

• Treatment failure within 180 days of randomisation.

  For in-patients, treatment failure is defined when a patient meets objective criteria for both inflammation and infection within a 5 day period. Meeting of the criteria for inflammation may precede or follow the date that criteria for infection were met (the first day of an eligible antibiotic treatment course). These criteria are: Criteria for Inflammation * A fever (≥ 37.8 degrees Celsius) or hypothermia (≤36 degrees Celsius), plus * A neutrophilia (\>7.5 x109/L) or neutropaenia (\<1.8 x 109/L), plus * A CRP over 100 mg/L PLUS, criteria for infection * Initiation of a new antibiotic treatment course of ≥ 5 days, or * A change in antibiotic treatment continued for ≥ 5 days, or * Initiation of a new antibiotic treatment, or a change in antibiotic treatment, and death within 5 days. * Bacteraemia with a recognised intestinal pathogen include: Anaerobes (e.g., Bacteroides), Enterobacterales and Streptococcus species. Assessed by blinded outcome committee

  180 days

Secondary Outcomes (15)

• Quality of life (EQ-5D-5L)

  180 days

• Cost effectiveness

  180 days

• Desirability Of Outcome Ranking (DOOR)

  180 days

• Number and type of source control procedures

  180 days

• Relapse of cIAI

  180 days

Study Arms (2)

Standard care

ACTIVE COMPARATOR

Clinician decided antibiotic treatment duration

Drug: Antibiotic - standard duration

Fixed-extended-duration antibiotics

EXPERIMENTAL

28 day antibiotic treatment duration

Drug: Antibiotic - fixed-extended-duration

Interventions

Antibiotic - standard duration DRUG

Clinician decided antibiotic and duration of treatment

Standard care

Antibiotic - fixed-extended-duration DRUG

Clinician decided antibiotic for a fixed duration of 28 days.

Fixed-extended-duration antibiotics

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarah Cockayne: lead
• University of York: collaborator
• University of Birmingham: collaborator
• Chesterfield Royal Hospital NHS Foundation Trust: collaborator
• University of Leeds: collaborator
• The Leeds Teaching Hospitals NHS Trust: collaborator

Study Sites (36)

Cwm Taf Morgannwg University Health Board,

Abercynon, United Kingdom

RECRUITING

NHS Grampian

Aberdeen, United Kingdom

RECRUITING

Hywel Dda University Health Board

Aberystwyth, United Kingdom

RECRUITING

Buckinghamshire Healthcare NHS Trust

Aylesbury, United Kingdom

RECRUITING

UniversityHospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

RECRUITING

Bolton NHS Foundation Trust

Bolton, United Kingdom

RECRUITING

United Lincolnshire Hospitals NHS Trust - Pilgrim Hospital Boston

Boston, United Kingdom

RECRUITING

University Hospitals Sussex NHS Foundation Trust

Brighton, United Kingdom

RECRUITING

North Bristol NHS Trust

Bristol, United Kingdom

NOT YET RECRUITING

North Cumbria Integrated Care NHS Foundation Turst

Carlisle, United Kingdom

RECRUITING

Chesterfield Royal Hospital NHS Foundation Trust

Chesterfield, United Kingdom

RECRUITING

University Hospital Coventry & Warwickshire

Coventry, United Kingdom

RECRUITING

County Durham and Darlington NHS Foundation Trust

Darlington, United Kingdom

RECRUITING

Northern Lincolnshire and Goole NHS Foundation Trust - Grimsby

Grimsby, United Kingdom

RECRUITING

Hull University Teaching Hospitals NHS Trust

Hull, United Kingdom

RECRUITING

East Suffolk and North Essex NHS Foundation Trust

Ipswich, United Kingdom

RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom

RECRUITING

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

RECRUITING

Chelsea and Westminster Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

Guys and St Thomas' NHS Foundation Trust

London, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, United Kingdom

RECRUITING

King'S College Hospital Nhs Foundation Trust

London, United Kingdom

RECRUITING

East Cheshire NHS Trust

Macclesfield, United Kingdom

RECRUITING

Manchester University NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Aneurin Bevan University Health Board

Newport, United Kingdom

ACTIVE NOT RECRUITING

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, United Kingdom

RECRUITING

Nottingham University Hospital NHS Trust

Nottingham, United Kingdom

RECRUITING

University Hospitals Plymouth NHS Trust

Plymouth, United Kingdom

RECRUITING

Lancashire Teaching Hospitals NHS Foundation Trust

Preston, United Kingdom

RECRUITING

Barking, Havering and Redbridge University Hospitals Nhs Trust

Romford, United Kingdom

RECRUITING

East Sussex Hospitals NHS Trust

Saint Leonards-on-Sea, United Kingdom

RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, United Kingdom

RECRUITING

North Tees and Hartlepool NHS Foundation Trust

Stockton-on-Tees, United Kingdom

RECRUITING

Sherwood Forest Hospitals NHS Foundation Trust

Sutton in Ashfield, United Kingdom

RECRUITING

Royal Cornwall Hospitals NHS Trust

Truro, United Kingdom

RECRUITING

University Hospitals Sussex NHS Foundation Trust

Worthing, United Kingdom

RECRUITING

Related Links

• Trial website

MeSH Terms

Conditions

Infections

Study Officials

• Andrew Kirby, MD

  University of Leeds

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Cockayne

CONTACT

01904 321736; ytu-extend-trial@york.ac.uk

Puvan Tharmanathan, PhD

CONTACT

01904 321844; puvan.nathan@york.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Fellow

Model Details: A phase III multicentre, open label, two-arm, parallel group, pragmatic, randomised controlled trial with internal pilot.

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 8, 2021
• Study Start: October 10, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (36)