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

NCT ID: NCT05148702

Last Updated: 2024-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1166 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-10

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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UK data suggests that current treatment for complicated intra-abdominal infections (cIAIs) results in unacceptably high rates of cIAI relapse and extra-abdominal infection. As a guiding rule, shorter antibiotic durations are important to combat antimicrobial resistance, but this is not true when these shorter courses need repeating and result in more days in hospital. Optimal care for patients should be our primary concern.

The EXTEND trial aims to find out whether a fixed extended duration of 28 days of antibiotics is superior to the current standard duration (typically 7-18 days) based on clinical outcomes and quality of life assessed over 180 days of follow up. Cost effectiveness will also be determined.

A target of 1166 patients will be recruited from ICUs and hospital in-patient wards across approximately 30 NHS trust hospitals. Only patients that are able provide consent (or those with a consultee able to confirm whether the patient would wish to be included in the study) can take part in the trial. They will receive antibiotics as prescribed by their treating clinician, but the duration of treatment will be determined by randomisation. Patients will have equal chance of randomisation to the standard care arm, in which the antibiotic duration will be determined by the treating clinician, or the intervention arm, a fixed duration of 28 days treatment.

Patients (or a personal consultee) will complete a quality of life questionnaire at baseline and 30, 60 and 180 days after randomisation. At follow-up timepoints they will also complete questionnaires on antibiotic use and health care resource use. Hospital notes will be used to collect data on inpatient admissions, relapse and further infections.

The study is Sponsored by the University of Leeds

Conditions

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Complicated Intra-abdominal Infection

Keywords

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infection antibiotics antibiotic resistance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A phase III multicentre, open label, two-arm, parallel group, pragmatic, randomised controlled trial with internal pilot.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard care

Clinician decided antibiotic treatment duration

Group Type ACTIVE_COMPARATOR

Antibiotic - standard duration

Intervention Type DRUG

Clinician decided antibiotic and duration of treatment

Fixed-extended-duration antibiotics

28 day antibiotic treatment duration

Group Type EXPERIMENTAL

Antibiotic - fixed-extended-duration

Intervention Type DRUG

Clinician decided antibiotic for a fixed duration of 28 days.

Interventions

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Antibiotic - standard duration

Clinician decided antibiotic and duration of treatment

Intervention Type DRUG

Antibiotic - fixed-extended-duration

Clinician decided antibiotic for a fixed duration of 28 days.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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 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.
* 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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of York

OTHER

Sponsor Role collaborator

University of Birmingham

OTHER

Sponsor Role collaborator

Chesterfield Royal Hospital NHS Foundation Trust

UNKNOWN

Sponsor Role collaborator

University of Leeds

OTHER

Sponsor Role collaborator

The Leeds Teaching Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Sarah Cockayne

OTHER

Sponsor Role lead

Responsible Party

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Sarah Cockayne

Research Fellow

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Andrew Kirby, MD

Role: PRINCIPAL_INVESTIGATOR

University of Leeds

Locations

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Cwm Taf Morgannwg University Health Board,

Abercynon, , United Kingdom

Site Status RECRUITING

NHS Grampian

Aberdeen, , United Kingdom

Site Status RECRUITING

Hywel Dda University Health Board

Aberystwyth, , United Kingdom

Site Status RECRUITING

Buckinghamshire Healthcare NHS Trust

Aylesbury, , United Kingdom

Site Status RECRUITING

UniversityHospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status RECRUITING

Bolton NHS Foundation Trust

Bolton, , United Kingdom

Site Status RECRUITING

United Lincolnshire Hospitals NHS Trust - Pilgrim Hospital Boston

Boston, , United Kingdom

Site Status RECRUITING

University Hospitals Sussex NHS Foundation Trust

Brighton, , United Kingdom

Site Status RECRUITING

North Bristol NHS Trust

Bristol, , United Kingdom

Site Status NOT_YET_RECRUITING

North Cumbria Integrated Care NHS Foundation Turst

Carlisle, , United Kingdom

Site Status RECRUITING

Chesterfield Royal Hospital NHS Foundation Trust

Chesterfield, , United Kingdom

Site Status RECRUITING

University Hospital Coventry & Warwickshire

Coventry, , United Kingdom

Site Status RECRUITING

County Durham and Darlington NHS Foundation Trust

Darlington, , United Kingdom

Site Status RECRUITING

Northern Lincolnshire and Goole NHS Foundation Trust - Grimsby

Grimsby, , United Kingdom

Site Status RECRUITING

Hull University Teaching Hospitals NHS Trust

Hull, , United Kingdom

Site Status RECRUITING

East Suffolk and North Essex NHS Foundation Trust

Ipswich, , United Kingdom

Site Status RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status RECRUITING

University Hospitals of Leicester NHS Trust

Leicester, , United Kingdom

Site Status RECRUITING

Chelsea and Westminster Hospital NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Guys and St Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status RECRUITING

King'S College Hospital Nhs Foundation Trust

London, , United Kingdom

Site Status RECRUITING

East Cheshire NHS Trust

Macclesfield, , United Kingdom

Site Status RECRUITING

Manchester University NHS Foundation Trust

Manchester, , United Kingdom

Site Status RECRUITING

Aneurin Bevan University Health Board

Newport, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, , United Kingdom

Site Status RECRUITING

Nottingham University Hospital NHS Trust

Nottingham, , United Kingdom

Site Status RECRUITING

University Hospitals Plymouth NHS Trust

Plymouth, , United Kingdom

Site Status RECRUITING

Lancashire Teaching Hospitals NHS Foundation Trust

Preston, , United Kingdom

Site Status RECRUITING

Barking, Havering and Redbridge University Hospitals Nhs Trust

Romford, , United Kingdom

Site Status RECRUITING

East Sussex Hospitals NHS Trust

Saint Leonards-on-Sea, , United Kingdom

Site Status RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

Site Status RECRUITING

North Tees and Hartlepool NHS Foundation Trust

Stockton-on-Tees, , United Kingdom

Site Status RECRUITING

Sherwood Forest Hospitals NHS Foundation Trust

Sutton in Ashfield, , United Kingdom

Site Status RECRUITING

Royal Cornwall Hospitals NHS Trust

Truro, , United Kingdom

Site Status RECRUITING

University Hospitals Sussex NHS Foundation Trust

Worthing, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Sarah Cockayne

Role: CONTACT

Phone: 01904 321736

Email: [email protected]

Puvan Tharmanathan, PhD

Role: CONTACT

Phone: 01904 321844

Email: [email protected]

Facility Contacts

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Role: primary

Related Links

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Other Identifiers

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ISRCTN 72819021

Identifier Type: REGISTRY

Identifier Source: secondary_id

NIHR131784

Identifier Type: -

Identifier Source: org_study_id