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Trial registered on ANZCTR


Registration number
ACTRN12615000545561
Ethics application status
Approved
Date submitted
23/04/2015
Date registered
28/05/2015
Date last updated
28/05/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Does the Pre-operative Use of Probiotic Prevent Ileus In Patients with Colorectal Cancer After Surgery ?
A Randomized, Double- Blind, Placebo-Controlled Trial.
Scientific title
Does the Pre-operative Use of Probiotic Prevent Ileus In Patients with Colorectal Cancer After Surgery ?
A Randomized, Double- Blind, Placebo-Controlled Trial.
Secondary ID [1] 286590 0
nil
Universal Trial Number (UTN)
U1111-1169-5655
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ileus in patients with colrectal cancer after surgery 294866 0
Condition category
Condition code
Oral and Gastrointestinal 295124 295124 0 0
Normal oral and gastrointestinal development and function
Cancer 295271 295271 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
STUDY DESIGN
Trial samples
Product, Dosage & Administration
The Probiotics
The probiotic which used in this study is Hexbio by B-Corbes. Hexbio is orange-flavoured granules, which prepared in sealed aluminium, foil pouches. Its’safety for consumption was ascertained with an Acute Oral Toxicty Test. The test was carried out by PSB Singapore and dated 06/04/2009.
Hexbio contains 6 strains of live bacteria:
1. Lactobacillus acidophilus
2. Lactobacillus casei
3. Lactobacillus lactis
4. Bifidobacterium bifidum
5. Bifidobacterium longum
6. Bifidobacterium infantis

These bacteria in this probiotic are all acid and bile resistant. They are highly compatible and able to adhere to the intestinal wall. The concentration of the bacteria in Hexbio is 30 billion colony-forming units.
Both probiotic and placebo were prepared in sealed aluminium foil pouches which labelled as A (Placebo) and B (Probiotics) respectively.
b) Differences between Probiotic & Placebo Preparation

Probiotic Placebo
1. Orange-flavoured granules Ascorbic acid
2. 30 billion colony forming units Skim milk powder
3. Lactose
4. Sealed in aluminium foil pouches
5. Labelled as ‘A’
6. Weight : 30g




Administration (Dosage & Duration)
The probiotic and placebo group administered their respective preparation 2 times per day for consecutive 7 days prior to operation day.
1st Dose : 0800H
2nd Dose : 2000H
The preparations were administered by diluting it with a glass (50cc) of room temperature water.

Instruction
i. Subjects are requested to consume trial samples for seven (7) days prior to date of operation.
ii. Patients will be followed up in the ward after surgery.



Recruitment
i. Subjects will be recruited from University Hospital of Malaya; or
ii. Subjects will be recruited from Surgical Clinic , Univeristy Hospital ; or
iii. Questionnaire will be administered to screen the fulfilment of the criteria prior to enrollment.
iv. Qualified subjects will be provided with information of the study and informed consent to be obtained.



Study duration
Length of the study was continued until patients consume normal diet or discharge. They were reviewed by dietician team for calorie & requirement intake

Diet during the study
i. Continue with the usual normal diets.
ii. Consume given trial samples (Probiotic or Placebo) 2 times a day, either before or after meal.
iii. Avoid consuming any other probiotics products to prevent confusion





Intervention code [1] 291707 0
Treatment: Other
Comparator / control treatment
Placebo
1. Orange-flavoured granules Ascorbic acid
2. Skim milk powder
3. Lactose
4. Sealed in aluminium foil pouches
5. Labelled as ‘A’
6. Weight : 30g
Control group
Placebo

Outcomes
Primary outcome [1] 294892 0
Return of normal gut function
as defined as the oral tolerance of 80% or more of calculated nutritional requirements (kcal /day) for a minimum consecutive period of 48 hours.

Caloric requirement was calculated according to the Harris Benedict equation:

Energy Requirement Equations

Basal Energy Expenditure (BEE)

Men: BMR = 66 + (13.7 X wt in kg) + (5 X ht in cm) - (6.8 X age in years)

Women: BMR = 655 + (9.6 X wt in kg) + (1.8 X ht in cm) - (4.7 X age in years)


Calculated Caloric Requirements (CCR):
CCR = BEE x activity factor (1.2) x stress factor (1.4)


Patients were followed up in the ward after surgery and reviewed by Dietitian Team for daily calorie & requirement intake




Timepoint [1] 294892 0
Length of the study was continued daily until return of normal gut function
Secondary outcome [1] 314290 0
Length of hospital stay assessed based on data from medical record.

Timepoint [1] 314290 0
Length of the study was continued daily until patients discharge.
Secondary outcome [2] 314738 0
Return of normal gut function assessed based on data from medical record including daily review of dietitian in the ward for calorie intake and requirement
Timepoint [2] 314738 0
Length of study was continued daily until patients discharge.
Secondary outcome [3] 314739 0
Postoperative / paralytic ileus after colorectal surgery
- any evidence of postoperative /paralytic ileus after colorectal surgery was assessed based on data from medical record.
Timepoint [3] 314739 0
Length of study was continued daily until patients discharge.
Secondary outcome [4] 314740 0
Unpleasant symptoms arise from ileus such as abdominal discomfort and pain assessed based on data from medical record
Timepoint [4] 314740 0
Length of study was continued daily untill patients discharge.
Secondary outcome [5] 314741 0
Early mobilisation and oral intake assessed based on data from medical record.
Timepoint [5] 314741 0
Length of study was continued daily until patients discharge.

Eligibility
Key inclusion criteria
i) The diagnosis of colorectal cancer was confirmed by biopsy and histiological test

ii) Patients whose biopsy confirmed colorectal cancer and scheduled to undergo colorectal surgery

iii) Age 18 years or above

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i. Acute intestinal obstruction
ii. Age <18 years
iii. Clinically significant immunodeficiency
iv. Evidence of infection
v. Undergoing emergency operation
vi. Gastric outlet obstruction
vii. Unable tolerate orally
viii. Pregnancy or lactating.
ix. Known lactose intolerance
x. Unstable psychological conditions or having psychic disorder.
xi. Severe medical illness such as end-stage renal failure, liver cirrhosis, advanced connective tissue disease, chronic congestive heart failure.
xii. Acute shock.
xiii. History of pre-existing arterial disease (recent myocardial infraction, stroke or TIA) and unstable angina pectoris.
xiv. Regular ingestion of any probiotics within 1 week prior to recruitment.


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 was done via central randomisation by computer. Stat Trek's Random Number Generator was used in randomising subjects into probiotic and placebo group.

i. Subjects were recruited from University Hospital of Malaya; or
ii. Subjects will be recruited from Surgical Clinic, University Hospital ; or
iii. Questionnaire was administered to screen the fulfillment of the criteria prior to enrollment.
iv. Qualified subjects were provided with information of the study and informed consent to be obtained.


The probiotic and placebo group administered their respective preparation 2 times per day for consecutive 7 days prior to operation day.
1st Dose : 0800H
2nd Dose : 2000H

The preparations were administered by diluting it with a glass (50cc) of room temperature water.


Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stat Trek's Random Number Generator was used in randomising subjects into probiotic and placebo group. It uses a statistical algorithm to produce random numbers
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
The sample size was calculated based on a previous study :
Liu Z, Qin H, Yang Z, et al. Randomised clinical trial: the effects of perioperative probiotic treatment on barrier function and post-operative infectious complications in colorectal cancer surgery—a double-blind study. Aliment Pharmacol Ther. 2011;33(1):50-63.

Calculated standardized differences :1.02631
The sample calculation demonstrated that a minimum 20 patients required in each arm of study to demonstrate a difference in return of gut function at 5 per cent level of significance with a power of 90 per cent.

Results for non-normally distributed continuous data were expressed as median and compared by means of the Mann-Whitney U test. Statistical significance was considered at the 5 per cent level Statistical data were analyzed by using SPSS for Windows version 21.

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 6843 0
Malaysia
State/province [1] 6843 0
Petaling Jaya, Selangor

Funding & Sponsors
Funding source category [1] 291153 0
University
Name [1] 291153 0
University of Malaya
Address [1] 291153 0
Jalan University, 50603, Kuala Lumpur
Country [1] 291153 0
Malaysia
Primary sponsor type
University
Name
University of Malaya
Address
Jalan University, 50603, Kuala Lumpur
Country
Malaysia
Secondary sponsor category [1] 289831 0
Government body
Name [1] 289831 0
Ministry of Health, Malaysia
Address [1] 289831 0
Blok E1, Kompleks E, Pusat Pentadbiran Persekutuan 62590 Putrajaya , Malaysia
Country [1] 289831 0
Malaysia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292729 0
University Malaya Medical Centre (UMMC) Ethical committee
Ethics committee address [1] 292729 0
Jalan University , 50603, Kuala Lumpur Malaysia
Ethics committee country [1] 292729 0
Malaysia
Date submitted for ethics approval [1] 292729 0
17/12/2011
Approval date [1] 292729 0
18/01/2012
Ethics approval number [1] 292729 0
360723

Summary
Brief summary
To study the efficacy of pre-operative use of probiotic in preventing ileus in patients with colorectal cancer after surgery.

Null Hypothesis
Pre-operative use of probiotic does not improve gut function and motility in patients with colorectal cancer after surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 56766 0
Dr Tan Chun Khui
Address 56766 0
University Malaya Medical Centre
Department of Surgery
Lembah Pantai, 59100, Kuala Lumpur, Malaysia.
Country 56766 0
Malaysia
Phone 56766 0
+60124999953
Fax 56766 0
Email 56766 0
cktan111@yahoo.com
Contact person for public queries
Name 56767 0
Dr Tan Chun Khui
Address 56767 0
University Malaya Medical Centre
Department of Surgery
Lembah Pantai, 59100, Kuala Lumpur, Malaysia.
Country 56767 0
Malaysia
Phone 56767 0
+60124999953
Fax 56767 0
Email 56767 0
cktan111@yahoo.com
Contact person for scientific queries
Name 56768 0
Dr Tan Chun Khui
Address 56768 0
University Malaya Medical Centre
Department of Surgery
Lembah Pantai, 59100, Kuala Lumpur, Malaysia.
Country 56768 0
Malaysia
Phone 56768 0
+60124999953
Fax 56768 0
Email 56768 0
cktan111@yahoo.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary