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Trial registered on ANZCTR


Registration number
ACTRN12615000249550
Ethics application status
Approved
Date submitted
24/02/2015
Date registered
18/03/2015
Date last updated
12/08/2019
Date data sharing statement initially provided
21/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Antibiotics in acute diverticulitis
Scientific title
Randomised double-blind placebo-controlled trial to evaluate the effect of antibiotics on length of hospital stay in uncomplicated acute diverticulitis in a tertiary hospital setting.
Secondary ID [1] 286247 0
None
Universal Trial Number (UTN)
U1111-1167-5630
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute diverticulitis 294303 0
Condition category
Condition code
Surgery 294625 294625 0 0
Other surgery
Infection 294626 294626 0 0
Studies of infection and infectious agents
Oral and Gastrointestinal 294704 294704 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention group will receive intravenous antibiotics followed by oral antibiotics.

Intravenous regimen (to commence following CT confirmation of uncomplicated AD, until afebrile for 24 hours)
Cefuroxime 750mg intravenous, every 8 hours
Metronidazole 500mg intravenous, every 8 hours

Oral antibiotics (on discharge or once afebrile for 24 hours)
Augmentin 625mg per oral, three times a day for 5-7 days
-patients will be telephoned at 30 days and adherence will be examined at this time
Intervention code [1] 291263 0
Treatment: Drugs
Comparator / control treatment
Initial intravenous placebo (containing lactose for colour), followed by tablet placebo (placebo manufactured by external laboratory)
Control group
Placebo

Outcomes
Primary outcome [1] 294388 0
Length of hospital stay
Timepoint [1] 294388 0
Hospital discharge from index admission
Secondary outcome [1] 313177 0
Patient symptom score (Global Symptom Score) and pain scores (on a scale of 1-10 as recorded by nursing staff)
-from patient medical records
Timepoint [1] 313177 0
First 48 hours in hospital
Secondary outcome [2] 313371 0
Readmission
-from patient medical records
Timepoint [2] 313371 0
1 month
Secondary outcome [3] 313372 0
Need for repeat imaging (CT scan)
-from patient medical records
Timepoint [3] 313372 0
Throughout index admission
Secondary outcome [4] 313373 0
Mortality
-from patient medical records
Timepoint [4] 313373 0
During index admission and 1 month following
Secondary outcome [5] 313572 0
serum markers of inflammation
-from patient medical records
Timepoint [5] 313572 0
Throughout index admission
Secondary outcome [6] 313573 0
Occurrence of complications (need for operation or percutaneous drainage)
-from patient medical records
Timepoint [6] 313573 0
Throughout index admission

Eligibility
Key inclusion criteria
1. Age > 18 years.
2. Current inpatient under the General Surgery service
3. Diagnosed with uncomplicated acute diverticulitis on CT scan within 24 hours of admission
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnancy.
2. Previous allergic reaction with cefuroxime, metronidazole or amoxicillin/clavulanic acid use
3. Steroid or immunomodulator use for more than 5 days prior to presentation
4. Greater than 1 week of regular, non-steroidal anti-inflammatory drug use prior to presentation
5. Inflammatory bowel disease
6. ASA of 4 or greater
7. CT evidence of complicated disease
8. Meets criteria for a diagnosis of SIRS

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will occur centrally at an external pharmacy where study medications are manfactured. We are working with an external pharmacy that has the capacity to make intravenous placebo. The hospital pharmacy did not have the capacity to make intravenous placebo for non-elective patients
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Screened patients who consent to enrolment in this study will be randomised, with the aim of allowing allocation to the antibiotic and placebo groups in a 1:1 ratio. The actual process of patient randomisation will be achieved using a computer-based random number generator. Heterogeneity will be dealt with by the randomisation process, and post hoc stratification analyses will be undertaken as a secondary outcome.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The study investigators have undertaken a retrospective review to enable a well-informed power calculation for this randomised control trial. This review examined all admissions for AD at Auckland City hospital over an 18 month period. There were 204 cases of uncomplicated cases of AD during this time, with a mean length of stay of 88.9hrs (SD 70.6) per episode. 20 of these patients were subsequently found to have had poor outcomes (longer hospital stay or need for procedural intervention). We aim to identify the patients who are at high risk for poorer outcomes through our exclusion criteria, which will slightly reduce our pool of potentially eligible patients.
Using these data, a power calculation was performed in order to determine the number of participants required in order to determine non-inferiority of the intervention. The distribution of these data was symmetric under a logarithmic (base 10) transformation (with SD 0.245).
A change in length of stay of 24 hours would be clinically significant for the patient and for hospital services. Assuming a non-inferiority margin of 24 hours, an independent-samples t-test on log-transformed length of stay data and common SD of 0.245 it was determined that 89 patients would be required in each arm to achieve 80% power and one-sided alpha-error of 0.025 .
We expect the rate of participation to be modest given that this is a trial of acutely unwell patients. After taking rate of participation and the potential for patients to drop-out into account, we aim to recruit 94 patients in each arm – 188 patients in total. As the retrospective study of a single centre carried out over 18 months yielded 204 potentially eligible patients, this is a feasible number to recruit over the same study duration over 3 centres, even after accounting for patients who will be excluded for being at increased risk of poorer outcomes.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2015
Actual
24/12/2015
Date of last participant enrolment
Anticipated
Actual
25/04/2019
Date of last data collection
Anticipated
Actual
25/05/2019
Sample size
Target
188
Accrual to date
Final
180
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 12482 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 24803 0
2145 - Westmead
Recruitment outside Australia
Country [1] 6684 0
New Zealand
State/province [1] 6684 0
Auckland

Funding & Sponsors
Funding source category [1] 290807 0
Charities/Societies/Foundations
Name [1] 290807 0
Auckland Medical Research Foundation
Country [1] 290807 0
New Zealand
Funding source category [2] 293944 0
Charities/Societies/Foundations
Name [2] 293944 0
Colorectal Surgical Society of Australia and New Zealand
Country [2] 293944 0
Australia
Primary sponsor type
University
Name
University of Auckland
Address
The University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 289494 0
Hospital
Name [1] 289494 0
Auckland City Hospital
Address [1] 289494 0
2 Park Road, Auckland 1142
Country [1] 289494 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292433 0
Health and Disability Ethics Committees
Ethics committee address [1] 292433 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 1010
Ethics committee country [1] 292433 0
New Zealand
Date submitted for ethics approval [1] 292433 0
26/02/2015
Approval date [1] 292433 0
16/06/2015
Ethics approval number [1] 292433 0

Summary
Brief summary
Aim
To determine whether the administration of an intravenous and oral antibiotic regimen is more effective than a placebo for reducing length of hospital stay, pain and symptoms of uncomplicated AD.

Hypothesis
That patients given the placebo will have a similar resolution of symptoms (as measured by patient reported scores) as those treated with antibiotics without an increase in recurrence or complications.

Primary Objective
To determine whether antibiotic administration results in a difference in length of hospital stay when compared to a placebo.

Secondary Objectives
To determine whether antibiotic administration results in a difference in; patient-reported symptom scores, length of stay, occurrence of complications, readmission within 30 days, symptoms of AD, and serum markers of inflammation when compared with patients receiving placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55262 0
Prof Ian Bissett
Address 55262 0
Department of Surgery
University of Auckland
ACH Support Building
Level 12, Room 12.085
Park Road, Grafton
Auckland 1023
Country 55262 0
New Zealand
Phone 55262 0
+64 21 347 442
Fax 55262 0
Email 55262 0
[email protected]
Contact person for public queries
Name 55263 0
Rebekah Jaung
Address 55263 0
Department of Surgery
University of Auckland
ACH Support Building
Level 12, Room 12.085
Park Road, Grafton
Auckland 1023
Country 55263 0
New Zealand
Phone 55263 0
+64 21 134 4600
Fax 55263 0
Email 55263 0
[email protected]
Contact person for scientific queries
Name 55264 0
Rebekah Jaung
Address 55264 0
Department of Surgery
University of Auckland
ACH Support Building
Level 12, Room 12.085
Park Road, Grafton
Auckland 1023
Country 55264 0
New Zealand
Phone 55264 0
+6421 134 4600
Fax 55264 0
Email 55264 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
individual participant data underlying published results only (de-identified)
When will data be available (start and end dates)?
Following publication of study data for upto 10 years from close of the trial
Available to whom?
case-by-case basis at the discretion of Principal investigator
Available for what types of analyses?
only to achieve the aims in the approved proposal
How or where can data be obtained?
access subject to approvals by Principal Investigator


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAntibiotics Do Not Reduce Length of Hospital Stay for Uncomplicated Diverticulitis in a Pragmatic Double-Blind Randomized Trial.2021https://dx.doi.org/10.1016/j.cgh.2020.03.049
N.B. These documents automatically identified may not have been verified by the study sponsor.