EXTENDed Antibiotic Durations Compared to Standard Durations for Patients With Complicated Intra-abdominal Infection.
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age16+
SponsorSarah Cockayne
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Antibiotic - standard duration
DrugClinician decided antibiotic and duration of treatment
Antibiotic - fixed-extended-duration
DrugClinician decided antibiotic for a fixed duration of 28 days.
Treatment groups
1,166 Participants
are divided into 2 treatment groupsGroup A: Standard careActive comparator 1 intervention
Group B: Fixed-extended-duration antibioticsExperimental treatment 1 intervention
Trial outcomes
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
Time frame
180 daysSecondary outcomes
1
Quality of life (EQ-5D-5L)
Participants will complete the EQ-5D-5L at baseline, and at 30, 90 and 180 days post-randomisation.
Time frame
180 days2
Cost effectiveness
Participants will complete health care resource use questionnaires at 30, 90 and 180 days after randomisation to record activity outside of hospital. Research teams will record data related to expenses as an inpatient.
Time frame
180 days3
Desirability Of Outcome Ranking (DOOR)
Patients will be categorised according to the worst outcome they experience over the 6 months follow up period using a four-level ordinal classification the Desirability Of Outcome Ranking (DOOR). The four levels will be C1 = No treatment failure, C2 = Treatment failure (as for the primary outcome), C3 = Treatment failure associated with sepsis (NEWS 6 in ward-based patients and SOFA 2 in ICU based patients) and C4 = Treatment failure associated with death.
Time frame
180 days4
Number and type of source control procedures
The total number and type of source control procedures measured by reviewing patient notes at 180 days after randomisation. The definition of source control used for this study is any procedure that stops the ongoing contamination of the peritoneal cavity and removes the majority of the contaminated intraperitoneal contents to the extent that no further acute interventions are felt to be necessary. The different types (radiological, surgical) and source control procedures of any type occurring in each randomised group will be compared using a proportional odds model, with fixed effects for allocation, the stratification factors and other prognostic baseline covariates, and random intercepts for study recruitment site.
Time frame
180 daysSponsors and contacts
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Sarah Cockayne
Lead sponsor
University of York
Sponsor institution
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
Source ClinicalTrials.gov