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Trial registered on ANZCTR


Registration number
ACTRN12624000748516p
Ethics application status
Submitted, not yet approved
Date submitted
13/03/2024
Date registered
17/06/2024
Date last updated
17/06/2024
Date data sharing statement initially provided
17/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
The impact of preoperative oral antibiotics on the microbiome and microbiology of the colon
Scientific title
The impact of preoperative oral antibiotics on the microbiome and microbiology of the colon
A study embedded into the Colorectal Anastomosis and Bacterial Eradication (CABE) trial
Secondary ID [1] 311715 0
none
Universal Trial Number (UTN)
U1111-1299-7148
Trial acronym
CABE_Micro
Linked study record
Australia Clinical Trials Registry Number (parent study): 12622000285752

Health condition
Health condition(s) or problem(s) studied:
colorectal cancer 333193 0
Condition category
Condition code
Cancer 329881 329881 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This observational sub-study is occurring as part of a randomised controlled trial (registered as ACTRN12622000285752) where participants are randomised to oral antibiotics (OAB) or placebo in addition to routine care as part of the participating patient's bowel preparation on the day before surgery. Broad spectrum Intravenous antibiotics (IV) will be administered according to individual hospital guidelines. IV antibiotics administered will have adequate aerobic and anaerobic antimicrobial coverage. The use of mechanical bowel preparation (MBP) and enemas will be determined according to individual hospital guidelines. The exposure to OAB will be randomised according to the parent trial protocol.
OAB Group
1. Standard pre-operative preparation for surgery, including the decision to use MBP or not, as per institutional protocol
2. OAB: 1 g neomycin and 400 mg metronidazole PO at 13:00, 14:00 and 20:00 on the day before surgery. No laboratory test will be used to monitor adherence.
The observational sub-study involves the additional collection of rectal swabs on the day before surgery, in theatre, five days postoperative or discharge whichever is sooner. For those that develop an anastomotic leak, a swab of the anastomosis will be taken at the time of treatment for the leak.
Intervention code [1] 328179 0
Not applicable
Comparator / control treatment
The control group is the Standard care group that receives standard pre-operative preparation for surgery and placebo as described in ACTRN12622000285752
Control group
Placebo

Outcomes
Primary outcome [1] 337649 0
Alpha diversity of the colonic microbiota,
Timepoint [1] 337649 0
one to two weeks before surgery (at preadmission), during surgery (primary timepoint), and five days after surgery or on discharge (whichever is sooner)
Primary outcome [2] 337650 0
The presence of Pseudomonas Aeruginosa (PSA)
Timepoint [2] 337650 0
one to two weeks before surgery (at preadmission), during surgery (primary timepoint), and five days after surgery or on discharge (whichever is sooner)
Primary outcome [3] 337816 0
Beta diversity of the colon microbiota
Timepoint [3] 337816 0
one to two weeks before surgery (at preadmission), during surgery (primary timepoint), and five days after surgery or on discharge (whichever is sooner)
Secondary outcome [1] 432685 0
Anastomotic leak (AL)
Timepoint [1] 432685 0
Leaks will be classified from the time of surgery as early: Developing 3 days or less after surgery, intermediate: Developing 4 to 7 days after surgery or late: Developing 8 days or more after surgery.
Secondary outcome [2] 432705 0
Incisional Surgical site infections
Timepoint [2] 432705 0
Standard wound checks will be conducted on day 5 post-operation or the day before discharge if the length of stay is less than five days. This will be followed by a patient reported outcome questionnaire (The Bluebelle wound healing questionnaire) at thirty days.
Secondary outcome [3] 432742 0
Serious Adverse events, defined as in Common Terminology Criteria for Adverse Events (CTCAE) v4 criteria. These include an event that leads to death or serious deterioration in the health of the subject resulting in life-threatening illness or injury or permanent impairment.
Timepoint [3] 432742 0
Daily whilst the participant is an inpatient and once the intervention is administered. Then once at 30 day follow up visit until resolution of the AE.
Secondary outcome [4] 432743 0
Foreseeable Adverse event. These are common side effects of oral Neomicina Salvat and Metronidazole. These include: nausea, vomiting diarrhea, bloating, headaches (common). Uncommon side effects include ototoxicity, nephrotoxicity, anaphylaxis, and peripheral neuropathy
Timepoint [4] 432743 0
Daily whilst the participant is an inpatient and once the intervention is administered. Then once at 30 day follow up visit until resolution of the AE.
Secondary outcome [5] 432744 0
Postoperative Ileus
Timepoint [5] 432744 0
Daily from the date of surgical procedure to day of discharge.
Secondary outcome [6] 432745 0
length of stay (LOS)
Timepoint [6] 432745 0
Once on the day of discharge.
Secondary outcome [7] 432746 0
Readmission to hospital
Timepoint [7] 432746 0
Once on the 30-day follow-up.
Secondary outcome [8] 432747 0
Postoperative complications not already mentioned
Timepoint [8] 432747 0
Daily from the time of the operative procedure until discharge, and then once on the 30-day follow-up visit.
Secondary outcome [9] 433380 0
PRIMARY OUTCOME - Presence of Enterococcus faecalis (ENF)
Timepoint [9] 433380 0
one to two weeks before surgery, during surgery (primary timepoint), three days after surgery, and five days after surgery or on discharge (whichever is sooner)
Secondary outcome [10] 433381 0
PRIMARY OUTCOME - Collagenase production of isolated bacterial strains
Timepoint [10] 433381 0
one to two weeks before surgery, during surgery (primary timepoint), three days after surgery, and five days after surgery or on discharge (whichever is sooner)

Eligibility
Key inclusion criteria
1. Patients undergoing elective colorectal resection with primary anastomosis – this includes open, laparoscopic, or robotic resections.
2. Above the age of 18
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Emergency surgery
2. Allergy to metronidazole or neomycin
3. Has received antibiotics in the preceding month before first sample collection
4. Pregnancy
5. Inability to consent
6. Post-Randomisation exclusion: No anastomosis performed
7. Patients having surgery with a rectal anastomosis will have swabs 1 and 2 performed, but will be excluded from having swabs 3 and 4 done.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sequential patients enrolled in the parent study will be invited to participate until we reach 15 patients in the following four groups:
a) Broad spectrum IV antibiotics only (IV)
b) IV and preoperative oral antibiotics (IV+OA)
c) IV and mechanical bowel preparation (IV+MBP)
d) IV and OA and MBP (IV+OA+MBP)
The statistics for the parent study are described in ACTRN12622000285752. The statistics for the microbiome and microbiology sub-study are described as follows:Alpha diversity will be calculated with Richness, Shannon index, and Simpson index. Comparison of alpha diversity will be performed with the Wilcoxon-Mann Whitney test. Beta diversity will be calculated with UniFrac and or Bray-Curtis, and analysed with principal component analysis and visualised with multi-dimensional scaling. Culture and collagenase will be analysed using the Chi squared test.
The following comparisons will be made:
1. Participants that fall into the different treatment groups will be compared between each other and over time.
Patients who suffer anastomotic leak will be compared against matched controls.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/07/2024
Actual
Date of last participant enrolment
Anticipated
30/08/2026
Actual
Date of last data collection
Anticipated
3/09/2026
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment outside Australia
Country [1] 26196 0
New Zealand
State/province [1] 26196 0
Otago and Canterbury

Funding & Sponsors
Funding source category [1] 316044 0
Charities/Societies/Foundations
Name [1] 316044 0
Lottery Health
Country [1] 316044 0
New Zealand
Funding source category [2] 316059 0
Government body
Name [2] 316059 0
Health Research Council
Country [2] 316059 0
New Zealand
Primary sponsor type
University
Name
Otago University
Address
Country
New Zealand
Secondary sponsor category [1] 318206 0
None
Name [1] 318206 0
Address [1] 318206 0
Country [1] 318206 0
Other collaborator category [1] 282976 0
Hospital
Name [1] 282976 0
Dunedin Hospital (Health New Zealand)
Address [1] 282976 0
Country [1] 282976 0
New Zealand
Other collaborator category [2] 282977 0
Hospital
Name [2] 282977 0
Christchurch Hospital (Health New Zealand)
Address [2] 282977 0
Country [2] 282977 0
New Zealand

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314866 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 314866 0
https://ethics.health.govt.nz/about/southern-health-and-disability-ethics-committee/
Ethics committee country [1] 314866 0
New Zealand
Date submitted for ethics approval [1] 314866 0
22/02/2024
Approval date [1] 314866 0
Ethics approval number [1] 314866 0

Summary
Brief summary
The setting is a multi-centre, double-blinded, randomised controlled trial comparing standard unit preparation with and without oral antibiotics in adult patients undergoing elective colorectal surgery with a planned anastomosis. One group will receive OAB and the other an identical appearing placebo capsules.
The observational sub-study will comprise patients who will provide samples for microbiome analysis. This will include four groups of 15 patients who will receive different types of bowel preparation and an analysis of patients with anastomotic leaks and matched controls.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132982 0
Dr John Woodfield
Address 132982 0
4th Floor Dunedin Hospital, Department of Surgical Sciences, 201 Great king St, Dunedin, 9054
Country 132982 0
New Zealand
Phone 132982 0
+64 276085111
Fax 132982 0
Email 132982 0
john.woodfield@otago.ac.nz
Contact person for public queries
Name 132983 0
Kari Clifford
Address 132983 0
4th Floor Dunedin Hospital, Department of Surgical Sciences, 201 Great king St, Dunedin, 9054
Country 132983 0
New Zealand
Phone 132983 0
+64 210668369
Fax 132983 0
Email 132983 0
kari.clifford@gmail.com
Contact person for scientific queries
Name 132984 0
Kari Clifford
Address 132984 0
4th Floor Dunedin Hospital, Department of Surgical Sciences, 201 Great king St, Dunedin, 9054
Country 132984 0
New Zealand
Phone 132984 0
+64 210668369
Fax 132984 0
Email 132984 0
kari.clifford@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
anonymised individual participant data
When will data be available (start and end dates)?
data will be available at the end of the trial, once we have published the data. The data will be unavailable 10 years following publication.
Available to whom?
to researchers upon reasonable requests
Available for what types of analyses?
available for meta analyses and other analyses looking at the study outcomes.
How or where can data be obtained?
Data can be obtained from the trial coordinator via email: kari.clifford@otago.ac.nz


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
No additional documents have been identified.