Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000285752
Ethics application status
Approved
Date submitted
10/12/2020
Date registered
15/02/2022
Date last updated
29/10/2024
Date data sharing statement initially provided
15/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Colorectal Anastomosis and Bacterial Eradication (CABE) Trial: The effect of pre-operative oral antibiotics on Anastomotic Leaks in Colorectal Surgery
Scientific title
Colorectal Anastomosis and Bacterial Eradication (CABE) Trial: The effect of pre-operative antibiotics on Anastomotic Leaks in Colorectal Surgery
Secondary ID [1] 302957 0
None
Universal Trial Number (UTN)
Trial acronym
CABE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anastomotic leaks 319987 0
Surgical Site Infections 325180 0
Urinary tract infections 325181 0
Respiratory infections 325182 0
Gastrointestinal infections 325183 0
Mortality 325184 0
Condition category
Condition code
Infection 317920 317920 0 0
Other infectious diseases
Surgery 318239 318239 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Both groups will receive standard hospital care, and this may vary according to the institutional protocol used at the treatment site, but may include:

1. Osmotic laxative satchets: 3 satchets - each satchet to be drunk with 250ml of water 1 day before the operation at 1200, 1400 and 1600
2. MRSA decolononisation: 2 x (4% chlorhexidine soap packets) - patients to use shower with 1 packet night before surgery and morning of surgery. If the soap packets were used incorrectly, chlorhexidine wipes will be used on the day of the surgery.
Intervention group – Oral antibiotics(OAB)
1. Pre-operative preparation for surgery, including decision to use Mechanical Bowel Preparation (MBP), MRSA decolonisation, both, or neither, as per institutional protocol and outlined above.
2. OAB: 1g neomycin and 400mg metronidazole at 1300, 1400 and 2000 on the preoperative day

Adherence will be monitored through noting the number of tablets taken.
Intervention code [1] 319244 0
Treatment: Drugs
Comparator / control treatment
The control group compromises of participants randomised to the standard of care with the addition of placebo pills. Placebo pills will comprise of glucose capsules.
Standard of care intervention will vary according to institutional protocols at different treatment sites, but may include:
1. Osmotic laxative satchets: 3 satchets - each satchet to be drunk with 250ml of water 1 day before the operation at 1200, 1400 and 1600
2. MRSA decolononisation: 2 x (4% chlorhexidine soap packets) - patients to use shower with 1 packet night before surgery and morning of surgery. If the soap packets were used incorrectly, chlorhexidine wipes will be used on the day of the surgery
3. Placebo pills - identical pills to the interventional pills to be taken at 1300, 1400 and 2200 day before surgery.

Adherence will be monitored through noting the number of tablets taken.
Control group
Placebo

Outcomes
Primary outcome [1] 325929 0
Incidence of any Anastomotic leak, defined as a defect in the bowel wall at the anastomotic site leading to leakage of intestinal contents. This can be either diagnosed radiologically, endoscopically or intra-operatively. They will be graded according to the International Study Group of Rectal Cancer proposed grading system for anastomotic leak:

1. Grade A: Radiological or clinical findings without associated symptoms or abnormal laboratory tests which is managed expectantly
a. Usually detected by routine contrast enema studies before closure of a temporary ileostomy/colostomy

2. Grade B: Leaks with signs and/or symptoms which requires nonoperative intervention including antibiotics and/or image-guide drainage
a. Clinical presentation may include abdominal and/or pelvic pain, and possibly abdominal distension and turbid/purulent rectal or vaginal discharge.
b. May have turbid/purulent or faecal drain contents depending on size of leakage. New enteric content through drain or fistula.
c. Imaging studies (contrast enema x-ray or CT with rectal contrast show leakage of the endoluminally administered contrast agent into the extraintestinal space, and potentially pelvic fluid collection)
d. For this study, 2 additional criteria will be included
i. Non-operative intervention which includes endoscopic procedures
ii. Suspicion of leak on radiology managed with antibiotics when no other infective causes found

3. Grade C: Leak with sign and/or symptoms which require an operative intervention which requires revision laparoscopic approach or laparotomy to control life-threatening sepsis, including either removal of anastomosis with end colostomy, or creation of a protective ileostomy.
a. Clinical presentation typically includes purulent/faecal drainage, severe abdominal pain, fever, signs of peritonitis. Notably elevated C-reactive protein, leukocytosis
b. Imaging studies show leakage at the anastomotic site and pelvic fluid collection.

Anastomotic leak grades will be analysed as a total, individually and together as Grade B and C.

Furthermore, leaks will be classified from the time of surgery
1. Early: Developing 3 days or less after surgery
2. Intermediate: Developing 4 to 7 days after surgery
3. Late: Developing 8 days or more after surgery
Timepoint [1] 325929 0
14 days and 30 days post-operation (primary timepoint)
Primary outcome [2] 339753 0
Incisional surgical site infections (iSSI)

Incisional Surgical Site Infection is defined by the Centres for Disease (CDC) definitions of superficial incisional and deep incisional SSI. To ensure that iSSI are not missed, standard wound checks will be conducted on day 5 post-operation as well as the day before discharge. Additional wound checks can be conducted at the discretion of the treating team. We would advocate for surgical teams to check the wound sites if any of the following arises:

1. Rise in inflammatory markers including white cell count and C-reactive protein
2. Febrile, tachycardic or hypotensive episodes
3. Wound dressings remain oozy
4. Patient complaining of redness and tenderness over the wound site.

Further patient-reported outcome measures (PROMs) will be collected from the patient during their post-operative clinic appointment 30 days after the surgery. The Bluebelle wound healing questionnaire will be given to the patient to be collected during their clinic appointment. Clinicians will need to be aware of any positive findings and thoroughly assess the wound site for surgical site infections.

Definitions for iSSI:

Superficial incisional SSI
1. Must occur within 30 days after any operative procedure and involve only the skin and subcutaneous tissue of incision
2. Patient must have one of the following
a. Purulent drainage from incision
b. Organisms identified from an aseptically obtained specimen
c. Superficial incision that is deliberately opened by a surgeon or other designee and culture or non-culture-based testing is not performed, and at least one of the following signs or symptoms: pain or tenderness; localised swelling; erythema; or heat
d. Diagnosis of a superficial incisional SSI by the surgeon or an attending physician or other designee
e. Significant erythema/cellulitis requiring treatment with antibiotics

Deep incisional SSI
1. Infection must occur within 30 or 90 days after the operative procedure and involve soft tissues of the incision (fascial and muscle layers). However for practicality purposes, this will only be measured at 30 days
2. Patient must have at least one of the following
a. Purulent drainage from the deep incision
b. A deep incision that spontaneously dehisces or is deliberately opened or aspirated by a surgeon, attending physician, or other designee, and the organism is identified by a culture or non-culture-based microbiologic testing method. Patient must have also one of the following: Fever, localised pain or tenderness.
c. Abscess of evidence of infection involving the deep incision that is detected on gross anatomic or histopathologic examination or imaging test.
Timepoint [2] 339753 0
30 days post-operative
Secondary outcome [1] 389565 0
Time fit for discharge

As assessed by the treating team prior to discharge. Surgical parameters such as symptoms and biochemistry markers will be used to assess fitness for discharge.
Timepoint [1] 389565 0
This will be assessed on the day that the treating team deems the patient fit for discharge.
Secondary outcome [2] 390580 0
Return to theatre for SSI debridement or washout

As assessed by the treating team. Surgical parameters such as symptoms, biochemistry markers and imaging will be used to assess return to theatre..
Timepoint [2] 390580 0
This will be assessed on the day that the treating team deems the patient requires re-operation for an SSI related incident.
Secondary outcome [3] 390581 0
Post- surgical complications/Infections including: pulmonary embolisms/deep vein thrombosis, urinary tract infections, respiratory infections, gastrointestinal infections

As assessed by the treating team. Surgical parameters such as symptoms, biochemistry markers and imaging will be used to diagnose post-surgical complications/infections according to ICD-10 classification.
Timepoint [3] 390581 0
This will be assessed on a daily basis during the course of the patient's in-patient stay in hospital. All events will be noted at 14 days and 30 days post-operation.
Secondary outcome [4] 390582 0
Mortality
Timepoint [4] 390582 0
This will be assessed on a daily basis during the course of the patient's in-patient stay in hospital. All events will be noted at 14 days and 30 days post-operation.

Eligibility
Key inclusion criteria
Inclusion criteria:
1. Patients undergoing elective open or laparoscopic colorectal resection
2. Able to give informed consent
3. Male or female patients 18 years of age or older, with no maximum
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 oral antibiotics
3. Inability to consent
4. Post-Randomisation exclusion: No anastomosis performed
5. Pregnancy

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will be determined through central randomisation with computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be conducted with a computer software. Using 2 sets of 2000 participants each (for a total of 4000 participants).
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
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis
To aim for a reduction of AL from 6% to 4%, we calculate we will need to have 2000 experimental and 2000 control participants to reject the null hypothesis that the infection rate for the experimental versus control participants are equal with a probably (power) of 0.80. This sample size calculation was based on an assumption that either the chi-square or Fischer’s exact test will be used to evaluate the null hypothesis . All continuous variable data will be tested using the Shapiro Wilks test for normality, all data which have a normal distribution will be described using mean ± standard deviation. Data that is not normally distributed will be described with median and the intra-quartile range. Comparisons between groups, for example patients treated with standard of care versus BPB1 will be made by t-tests and analysis of variance (ANOVAs) for normally distributed data or the non-parametric equivalents Wilcoxon–Mann Whitney and Kruskal Wallis test for non-normally distributed data. Alternatively, we may use regression analysis (Generalised linear mixed models (GLMM) which can be used with non-normally distributed data.

Categorical data will be described as frequency (percentage) and compared using Fisher’s exact test or Chi squared test as appropriate. Investigation of what factors may statistically significantly modify or predict outcomes such as the patient’s recent medical history or their post-operative care will be investigated using regression analysis. The type of regression analysis will depend on the nature of the variables (whether continuous, interval or categorical, and their distribution) and how many independent and dependent variables are being compared (multivariate and/or multiple regression). Only 2-sides tests will be used, and p values of <0.05 deemed significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2024
Actual
Date of last participant enrolment
Anticipated
1/11/2026
Actual
Date of last data collection
Anticipated
30/07/2026
Actual
Sample size
Target
4000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 18156 0
Dandenong Hospital - Dandenong
Recruitment hospital [2] 18157 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 18158 0
Frankston Hospital - Frankston
Recruitment postcode(s) [1] 32155 0
3199 - Frankston
Recruitment postcode(s) [2] 36714 0
3084 - Heidelberg
Recruitment postcode(s) [3] 36715 0
3175 - Dandenong
Recruitment outside Australia
Country [1] 26659 0
New Zealand
State/province [1] 26659 0
New Zealand-wide

Funding & Sponsors
Funding source category [1] 307375 0
Hospital
Name [1] 307375 0
Department of Colorectal Surgery, Dandenong Hospital, Monash Health
Country [1] 307375 0
Australia
Funding source category [2] 317720 0
Charities/Societies/Foundations
Name [2] 317720 0
Lottery Health Grant
Country [2] 317720 0
New Zealand
Primary sponsor type
Individual
Name
Mr Asiri Arachchi
Address
Department of Colorectal Surgery, Dandenong Hospital, Monash Health, Victoria, Australia
135 David St, Dandenong VIC 3175, Victoria, Australia
Country
Australia
Secondary sponsor category [1] 308031 0
Individual
Name [1] 308031 0
Mr Hanumant Chouhan
Address [1] 308031 0
Colorectal Surgery, Peninsula Private Hospital
525 McClelland Dr, Frankston VIC 3199, Victoria, Australia
Country [1] 308031 0
Australia
Other collaborator category [1] 283269 0
Individual
Name [1] 283269 0
Dr Kari Clifford
Address [1] 283269 0
Country [1] 283269 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307462 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 307462 0
Ethics committee country [1] 307462 0
Australia
Date submitted for ethics approval [1] 307462 0
21/10/2020
Approval date [1] 307462 0
27/01/2022
Ethics approval number [1] 307462 0
RES-20-0000-777A
Ethics committee name [2] 316411 0
Central Health and Disability Ethics Committee
Ethics committee address [2] 316411 0
Ethics committee country [2] 316411 0
New Zealand
Date submitted for ethics approval [2] 316411 0
09/01/2024
Approval date [2] 316411 0
13/02/2024
Ethics approval number [2] 316411 0
2024 Full 18109

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107318 0
Mr Asiri Arachchi
Address 107318 0
Department of Colorectal Surgery, Dandenong Hospital, Monash Health, Victoria, Australia
135 David St, Dandenong VIC 3175
Country 107318 0
Australia
Phone 107318 0
+61 406018279
Fax 107318 0
Email 107318 0
[email protected]
Contact person for public queries
Name 107319 0
Asiri Arachchi
Address 107319 0
Department of Colorectal Surgery, Dandenong Hospital, Monash Health, Victoria, Australia
135 David St, Dandenong VIC 3175
Country 107319 0
Australia
Phone 107319 0
+61 406018279
Fax 107319 0
Email 107319 0
[email protected]
Contact person for scientific queries
Name 107320 0
Asiri Arachchi
Address 107320 0
Department of Colorectal Surgery, Dandenong Hospital, Monash Health, Victoria, Australia
135 David St, Dandenong VIC 3175
Country 107320 0
Australia
Phone 107320 0
+61 406018279
Fax 107320 0
Email 107320 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
9983Informed consent form    381065-(Uploaded-08-02-2022-09-24-46)-Study-related document.docx
14980Ethical approval    381065-(Uploaded-08-02-2022-09-25-01)-Study-related document.pdf



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.