Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001343998
Ethics application status
Approved
Date submitted
27/09/2020
Date registered
14/12/2020
Date last updated
3/04/2023
Date data sharing statement initially provided
14/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Probiotic use and post-operative recovery following appendicectomy in children.
Scientific title
The use of probiotics in supporting post-operative recovery in children following appendicectomy.
Secondary ID [1] 302415 0
Nil known.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Appendicitis 319210 0
Condition category
Condition code
Surgery 317179 317179 0 0
Other surgery
Oral and Gastrointestinal 317595 317595 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
Children (4-13 -years) with simple (non-perforated) and complicated (perforated) appendicitis will be randomly allocated to the intervention group (probiotic) following appendicectomy.
Children with simple (non-perforated) appendicitis will undergo appendectomy followed by 2 post-operative doses of intravenous antibiotics; patients will receive once daily oral probiotic supplement or placebo control for 4 weeks.
Children with complicated (perforated appendicitis) will undergo appendectomy followed by 5 days of intravenous antibiotics. Patients will receive once daily oral probiotic supplement or placebo control for 4 weeks.
Probiotics will be taken orally and provided in sachets (1.5 g in total) and composed of:
- 50% L. helveticus (R52); (CFU count =2.5×10*9)
- 12.5% B. bifidum (R71); (CFU count =0.625×10*9)
- 12.5% B. longum subsp. infantis (R33); (CFU count =0.625×10*9)
- 25% breve (M16V); (CFU count =1.25×10*9)

Duration of administration will be 4 weeks, starting on the day the patients will have their first bowel motion following surgery.

Adherence to the intervention will be confirmed at the time when patients are seen for the post-operative follow-up and by return of unused probiotics/placebo
Intervention code [1] 318697 0
Treatment: Other
Comparator / control treatment
Children (4-13 -years) with simple and complicated (perforated) appendicitis will be randomly allocated to the placebo group following appendicectomy.
The placebo product will be taken orally and prepared to match the probiotics in appearance and odour, and each sachet will contain 1.5 g (total) of potato starch and maltodextrin.

Duration of administration will be 4 weeks, starting on the day the patients will have their first bowel motion following surgery.

Adherence to the intervention will be confirmed at the time when patients are seen for the post-operative follow-up and by return of unused probiotics/placebo
Control group
Placebo

Outcomes
Primary outcome [1] 325255 0
Incidence (number of episodes per day) of antibiotic associated diarrhoea (AAD) after post-appendicectomy intravenous antibiotic administration.
This outcome will be assessed from data-linkage to medical records.
Timepoint [1] 325255 0
Four weeks after taking the first probiotic/placebo. The first day will be when the patient has their first bowel motion after appendicectomy.
Primary outcome [2] 325640 0
Duration (number of days) of antibiotic associated diarrhoea (AAD) after post-appendicectomy intravenous antibiotic administration.
This outcome will be assessed from data-linkage to medical records.
Timepoint [2] 325640 0
Four weeks after taking the first probiotic/placebo. The first day will be when the patient has their first bowel motion after appendicectomy
Secondary outcome [1] 387352 0
Incidence of post-operative intra-abdominal abscess formation obtained from the hospital records.
Timepoint [1] 387352 0
Within fourteen days after the appendicectomy.
Secondary outcome [2] 388651 0
Level of stress/anxiety post-surgery using the standardised Emotionality Activity Sociability and Impulsivity (EASI) questionnaire.
Timepoint [2] 388651 0
Four weeks after taking the first probiotic/placebo. The first day will be when the patient has their first bowel motion after appendicectomy.
Secondary outcome [3] 388652 0
Time to return to school; participant-reported outcome.
Timepoint [3] 388652 0
From time of appendicectomy.
Secondary outcome [4] 388653 0
Microbial diversity measured as number of viable species in stools sample.
Timepoint [4] 388653 0
Two and four weeks after taking the first probiotic/placebo. The first day will be when the patient has their first bowel motion after appendicectomy.

Eligibility
Key inclusion criteria
1. Patients aged 4-13 years
2. No associated co-morbidities (ASA 1)
3. Undergoing laparoscopic appendicectomy for simple (non-perforated) or complicated (perforated) appendicitis
Minimum age
4 Years
Maximum age
13 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any associated co-morbidities (ASA 2 and above as confirmed independently by the anaesthetist and surgeon prior to appendicectomy; if disagreement a third doctor, anaesthetist or surgeon, will be consulted)
2. Prior antibiotic use within the previous 3 months
3. Previous history of significant gastrointestinal conditions (e.g. IBD, etc.) or metabolic conditions (e.g. diabetes mellitus) even if well controlled
4. Immunocompromised patients or patients taking immunosuppressant drugs
5. Overseas travel within the last 3 months

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)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomized according to weighted minimization: variables for minimization will include: gender, weight, age, simple/complicated appendicitis.
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Results will be analyzed after data extraction with dedicated statistical software. Data will be expressed as mean ± SD, median (range), interquartile range (IQR), count number, or percentages, as indicated. The D’Agostino and Pearson normality test will be used to evaluate the normal distribution of continuous variables. Unpaired Student’s t, Mann–Whitney U, Chi-squares, or Fischer’s exact test will be used where appropriate to identify differences between the two groups for continuous or categorical variables. Multiple regression analysis will be used to identify factors leading to AAD post-operatively. Sub analysis will be performed to look for difference in incidence of AAD according to the duration of the antibiotic therapy.
Statistical support will be sought from Monash University as required.

For the primary analysis, in order to maintain the statistical power of the original study population, all subjects will be included in the groups to which they were randomly assigned, even if they did not complete or even receive the allocated treatment ("intention to treat") analysis. This analysis will allow to preserves baseline comparability and will provide control of confounding by known and unknown confounders. Retention of all subjects in the analysis will reduce bias.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2021
Actual
1/06/2021
Date of last participant enrolment
Anticipated
31/05/2024
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
266
Accrual to date
115
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17656 0
Monash Children’s Hospital - Clayton
Recruitment postcode(s) [1] 31502 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 306835 0
Commercial sector/Industry
Name [1] 306835 0
H&H Group
Country [1] 306835 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Road
Clayton
Victoria 3168
Country
Australia
Secondary sponsor category [1] 307397 0
None
Name [1] 307397 0
Address [1] 307397 0
Country [1] 307397 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306997 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 306997 0
Ethics committee country [1] 306997 0
Australia
Date submitted for ethics approval [1] 306997 0
02/11/2020
Approval date [1] 306997 0
10/11/2020
Ethics approval number [1] 306997 0
RES-20-0000-793A

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

Contacts
Principal investigator
Name 105690 0
Dr Maurizio Pacilli
Address 105690 0
Monash Children's Hospital
246 Clayton Road
Clayton
Victoria 3168
Country 105690 0
Australia
Phone 105690 0
+61 385723837
Fax 105690 0
Email 105690 0
[email protected]
Contact person for public queries
Name 105691 0
Maurizio Pacilli
Address 105691 0
Monash Children's Hospital
246 Clayton Road
Clayton
Victoria 3168
Country 105691 0
Australia
Phone 105691 0
+61 385723837
Fax 105691 0
Email 105691 0
[email protected]
Contact person for scientific queries
Name 105692 0
Maurizio Pacilli
Address 105692 0
Monash Children's Hospital
246 Clayton Road
Clayton
Victoria 3168
Country 105692 0
Australia
Phone 105692 0
+61 385723837
Fax 105692 0
Email 105692 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
Data might generate intellectual property.


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.