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Trial registered on ANZCTR


Registration number
ACTRN12621000295842p
Ethics application status
Not yet submitted
Date submitted
11/12/2020
Date registered
18/03/2021
Date last updated
18/03/2021
Date data sharing statement initially provided
18/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Do Synbiotics Reduce Infections in Foregut Surgery?
Scientific title
Do Synbiotics Reduce Infections in Adults undergoing Major Foregut Surgery?
Secondary ID [1] 302488 0
Nil Known
Universal Trial Number (UTN)
The Universal Trial Number (UTN) is U1111-1259-3263
Trial acronym
DISCO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postoperative Infection 319327 0
Wound Infection 319328 0
Pneumonia 319329 0
Anastomotic Leak 319330 0
Intra-abdominal Collection 319331 0
Urinary Tract Infection 319332 0
Post-operative Ileus 319333 0
Intestinal Permeability 319339 0
Systemic Inflammation 319340 0
Condition category
Condition code
Surgery 317295 317295 0 0
Other surgery
Diet and Nutrition 317296 317296 0 0
Other diet and nutrition disorders
Infection 318397 318397 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Progood premium probiotics and prebiotic preparation. It contains 30 billion of the probiotic strains Lactobacillus acidophilus, and Bifidobacterium lactis. It contains the prebiotics as folllows:
- 1.4 grams of dietary fibre (aribinogalactan)
- 1.3 grams of Inulin
- 1.8 grams of Trehalose
Prepared as a 5g scoop of the powdered concentrate that is reconstituted with water and taken enterally. Participants will take 1 scoop daily for 14 days prior to surgery, and 1 scoop daily for 14 days after the surgery.
Patients are provided with a handout with checkboxes for them to indicate which days the treatment was ingested.
Intervention code [1] 318784 0
Treatment: Other
Comparator / control treatment
Placebo
- Maltodextrin powder that is reconstituted with water and taken enterally
Control group
Placebo

Outcomes
Primary outcome [1] 325357 0
Infections (any infection) which will be assessed by clinical and research staff during weekly unit meetings, from medical records, imaging reports, and microbiology reports. This will be prospectively collected and recorded in a RedCaps database.
Timepoint [1] 325357 0
Within the first 30 days postoperatively
Secondary outcome [1] 387617 0
Time to first bowel movement postoperatively which will be assessed via the stool chart from the medical records, or patient self-report if discharged prior to first bowel movement postoperatively.
Timepoint [1] 387617 0
Within the first 30 days postoperatively
Secondary outcome [2] 387618 0
Length of stay (days) in intensive care assessed via medical records.
Timepoint [2] 387618 0
In the first 30 days postoperatively
Secondary outcome [3] 387619 0
Length of hospital stay (Days) assessed via medical records.
Timepoint [3] 387619 0
In the first 30 days postoperatively
Secondary outcome [4] 387620 0
Duration of antibiotic therapy (days) assessed via medical records.
Timepoint [4] 387620 0
Within the first 30 days postoperatively
Secondary outcome [5] 387621 0
Mortality
Timepoint [5] 387621 0
Within the first 30 days postoperatively
Secondary outcome [6] 387622 0
Changes in faecal microbiota
- samples will be analysed via metagenomic sequencing to provide information about microbiotal colonies and allow comparison across time and across the two intervention groups
Timepoint [6] 387622 0
3 samples will be taken
- 1 prior to starting the intervention (synbiotic) 14 days preoperatively
- within 3 days of surgery; and
- day 5 postoperatively, or the first bowel motion after postoperative day 5
Secondary outcome [7] 387623 0
Whether there are differences in markers of intestinal permeability between the two groups
Serum samples will be collected to assess circulating lipopolysaccharide levels which are a marker of intestinal permeability.
Timepoint [7] 387623 0
2 blood samples are taken:
Sample 1: on day of surgery (preoperatively)
Sample 2: postoperative day 5 OR day of discharge, whichever is earlier.
Secondary outcome [8] 391259 0
Whether there are differences in markers of systemic inflammation between the two groups.
Serum samples will be analysed for tumour necrosis factor-alpha (TNFa), interleukin 6 (IL-6), and interferon-gamma (IFN-gamma) levels as markers of inflammation.
Timepoint [8] 391259 0
2 blood samples are taken:
Sample 1: on day of surgery (preoperatively)
Sample 2: postoperative day 5 OR day of discharge, whichever is earlier.

Eligibility
Key inclusion criteria
Patients eligible for participation in this trial include all adult patients undergoing elective major foregut surgery at St Vincent’s Public and St Vincent’s Private hospital in Melbourne.
Inclusion Criteria
- Adults older then 18 years old
- Scheduled for any major foregut operation for any indication including oesophagectomy, total gastrectomy, subtotal gastrectomy, pancreaticoduodenectomy, any type of pancreatectomy, splenectomy, liver resection, major bile duct resection
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria
- Inoperable tumours resulting in major resection not proceeding
- Patient refusal to participate in the study
- Emergency Surgery
- Allergy to probiotics or prebiotics

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 will be concealed. Sequentially numbered, opaque, sealed envelopes will be utilised as the method of allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation will be performed using a randomisation table created by computer software (i.e. computerised sequence generation).
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
Sample size was predetermined using a power analysis based on the observed postoperative infectious incidence in our database of 31% and a 50% risk reduction in infectious complications due to the synbiotic. This risk reduction was conservatively based on the outcome of meta-analyses of synbiotics in general surgical operations and randomised control trials of probiotics and synbiotics in major foregut surgery. Using STATA 9.0 statistical software (College Station, Tx, USA), a minimum sample size of 258 patients (129 in each group) to achieve 80% power (ß = 0.2) and 5% significance level (a = 0.05) is required.

Statistical analysis will be performed using Stata 9.0 (College Station, TX, USA) using an intention-to-treat model. Normally distributed continuous data will be compared using Student’s t test while categorical data will be compared using chi-square test and Fisher’s exact test. Differences will be considered significant at p < 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17756 0
St Vincent's Private Hospital - Fitzroy
Recruitment hospital [2] 17813 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 31619 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 306914 0
Hospital
Name [1] 306914 0
St Vincent's Hospital Melbourne Research Endowment Fund
Address [1] 306914 0
41 Victoria Parade
Fitzroy VIC 3065
Country [1] 306914 0
Australia
Funding source category [2] 307729 0
Charities/Societies/Foundations
Name [2] 307729 0
Surgeons Impact Fund
Address [2] 307729 0
Level 2, 456 St Kilda Road, Melbourne VIC 3004
Country [2] 307729 0
Australia
Primary sponsor type
Individual
Name
Amanda Nikolic
Address
St Vincent's Hospital
41 Victoria Parade
Fitzroy VIC 3065
Country
Australia
Secondary sponsor category [1] 307524 0
None
Name [1] 307524 0
Address [1] 307524 0
Country [1] 307524 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 307064 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 307064 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy,
Victoria, 3065
Ethics committee country [1] 307064 0
Australia
Date submitted for ethics approval [1] 307064 0
13/04/2021
Approval date [1] 307064 0
Ethics approval number [1] 307064 0

Summary
Brief summary
The perioperative administration of synbiotics (a combination of probiotics and prebiotics) has been associated with a relative risk reduction in postoperative infectious complications of 50% for patients undergoing general surgery.
Major foregut surgery includes oesophagectomy, gastrectomy, distal pancreatectomy, pancreaticoduodenectomy, and liver resections. These operations have a relatively high incidence of postoperative infections complications. From our locally maintained prospective database at St Vincent’s Hospital, the rate of infectious complications following major foregut surgery is 31%. This patient population will have preoperative dysbiosis due to the underlying pathology, neoadjuvant chemotherapy and radiotherapy, medications including antibiotics, weight loss, stress, and diet. They could gain significantly from interventions aimed at improving their microbiota and clinical outcomes.
We propose a randomised, placebo-controlled, double-blinded trial to assess perioperative synbiotic administration's effectiveness on reducing postoperative infections in major foregut surgery patients. Additional clinical outcomes will assess the impact of synbiotics on time to first bowel movement, length of stay in intensive care, length of hospital stay, antibiotic therapy duration, and mortality. We will also perform a scientific examination of faecal microbiota and assess intestinal permeability and systemic inflammation. By examining whether changes in clinical outcomes are correlated with alterations in these measures, we aim to understand the mechanism of action of synbiotics further.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105902 0
Mr Michael Hii
Address 105902 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy,
Victoria, 3065
Country 105902 0
Australia
Phone 105902 0
+61 392312211
Fax 105902 0
Email 105902 0
michael.hii@svha.org.au
Contact person for public queries
Name 105903 0
Dr Amanda Nikolic
Address 105903 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy,
Victoria, 3065
Country 105903 0
Australia
Phone 105903 0
+61 392312211
Fax 105903 0
Email 105903 0
synbiotics.in.surgery@gmail.com
Contact person for scientific queries
Name 105904 0
Dr Amanda Nikolic
Address 105904 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy,
Victoria, 3065
Country 105904 0
Australia
Phone 105904 0
+61 392312211
Fax 105904 0
Email 105904 0
synbiotics.in.surgery@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Investigators preference
What supporting documents are/will be available?
No other documents available
Summary results
No Results