Clinical trial NCT03816774: Effect of Adding Simethicone to Split-dose Polyethylene Glycol for Bowel Preparation in a Screening Colonoscopy Setting
Official title: Effect of Adding Simethicone to a Split Regimen of Polyethylene Glycol for Bowel Preparation in a Colorectal Cancer Screening Colonoscopy Setting: an Endoscopist-blinded Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colo-rectal Cancer
Colonic Neoplasms
Keywords: screening colonoscopy
colo-rectal cancer
simethicone
split-dose polyethylene glycol
adequate bowel preparation
Lead sponsor: Portuguese Oncology Institute, Coimbra
Sponsor class: OTHER
First posted: 2019-01-25
Enrollment: 412
Sex: ALL
Minimum age (years): 50
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Colonoscopy is currently accepted as the gold standard in screening, surveillance and prevention for colorectal cancer (CRC), and therefore, its quality is a major priority.

The quality of colonoscopy is greatly dependent on the quality of the bowel preparation. Standard bowel cleansing includes a low-fibre diet on the day preceding the exam and a split regimen of 4 litres of polyethylene glycol (PEG) solution.

In order to improve bowel cleansing some additional measures are available. Simethicone is an inexpensive and safe antifoaming agent that reduces the surface tension of air bubbles, theoretically presenting several benefits such as increased tolerability to the preparation, thereby improving the quality of the preparation and, secondly, adenoma detection (ADR) and cecal intubation rates (CIR). However, its role remains controversial, with some publications supporting its administration and others failing to demonstrate clear benefits.

The main aim of this study is to assess if addition of simethicone to a split-dose cleansing regimen of 4 litres of PEG improves adequate bowel preparation rate.

Detailed description: a. Study type: Endoscopist-blinded randomized controlled trial i. Prospective inclusion of patients scheduled for a colonoscopy by nationwide CRC screening program after a positive faecal immunochemical test.

ii. Randomization by computer generated tables. iii. Allocation concealment by sealed, opaque envelopes. iv. Endoscopist-blinded: endoscopist blinded to the group allocation. v. Patient informed about its bowel cleansing regimen.

b. Selection participant method: i. Inclusion by invitation of patients aged between 50 and 74 years, inclusive, scheduled for colonoscopy by nationwide CRC screening program after a positive faecal immunochemical test. ii. Exclusion criteria for nationwide CRC screening program: previous diagnosis of CRC, presence of known genetic susceptibility syndromes related with CRC, personal history of inflammatory bowel disease, presence of gastrointestinal complaints (significant changes in gastrointestinal transit in the last 6 months or evidence of gastrointestinal bleeding), a normal colonoscopy in the last 10 years and a normal flexible sigmoidoscopy in the last 5 years. Exclusion criteria of this study also include: known or suspected gastrointestinal obstruction or perforation, toxic megacolon, major colonic resection, pregnant or at risk of becoming pregnant and lactating women, known or suspected hypersensitivity to the active or other ingredients.

c. Sample size: i. 412 (2 groups of 206 patients). ii. To improve adequate bowel preparation rate (primary outcome) from 85% (value from the investigator's own database) to 95% (target standard suggested by ESGE) and assuming a normal distribution and a power of 90% (α=0.05), the calculated sample size of each of the 2 groups was 188; allowing for a 10% dropout rate, the sample size is 206 per group (412 patients overall). Adequate bowel preparation is defined as total. Boston Bowel Preparation Scale ≥6 and ≥2 in each segment. The chosen scale is the most systematically validated and appropriate for the clinical setting.

d. Procedures and data collection methods: Form sheets filled by the endoscopist about intraprocedural measures and by the nurse about patient compliance and tolerability to the prescribed cleansing regimen.

e. Analysed variables: i. Primary outcome: adequate bowel preparation rate. ii. Secondary outcomes: ADR, CIR, compliance and tolerability related to the bowel cleansing regimen. iii. Patient characteristics and other variables: age, gender, degree of mucosal bubble reported by a comprehensive scoring used by previous studies (grade 0: no bubbles; 1: minimal or occasional bubbles (must be actively sought); 2: moderate or obviously present; 3: severe or so many bubbles that vision is obscured), withdrawal time, polyp detection rate and complications rate.

f. Statistical analysis: i. Performed using statistical software IBM SPSS Statistics, Version 25.0. Armonk, NY: IBM Corp. ii. Continuous variables are reported as mean and standard deviation or median and interquartile range, if they have normal or not normal distribution, respectively; categorical variables as absolute and relative frequency. iii. Continuous variables are compared between two groups using Student's T test if they have a normal distribution and homogeneity of variance or Mann-Whitney U if these conditions are not met. Categorical variables are compared using Pearson's X2 test or Fisher test. iv. All hypotheses are two-tailed and a P-value\<0.05 is considered statistically significant.

Eligibility criteria: Inclusion criteria:

* consecutive patients scheduled for colonoscopy by nationwide CRC screening program after a positive faecal immunochemical test,
* signed informed consent.

Exclusion criteria:

* previous diagnosis of CRC,
* presence of known genetic susceptibility syndromes related with CRC,
* personal history of inflammatory bowel disease,
* presence of gastrointestinal complaints (significant changes in gastrointestinal transit in the last 6 months or evidence of gastrointestinal bleeding),
* a normal colonoscopy in the last 10 years and a normal flexible sigmoidoscopy in the last 5 years,
* known or suspected gastrointestinal obstruction or perforation, toxic megacolon, major colonic resection,
* pregnant or at risk of becoming pregnant and lactating women,
* known or suspected hypersensitivity to the active or other ingredients.

Primary outcomes:
measure: Adequate bowel preparation rate
timeFrame: 1 day (during colonoscopy)
Secondary outcomes:
measure: Adenoma detection rate
timeFrame: Within 30 days from colonoscopy date
measure: Cecal intubation rate
timeFrame: 1 day (during colonoscopy)
measure: Compliance to the bowel cleansing regimen
timeFrame: 1 day (immediately before colonoscopy)
measure: Tolerability to the bowel cleansing regimen:questionnaire
timeFrame: 1 day (immediately before colonoscopy)
Other outcomes:
measure: Degree of mucosal bubble
timeFrame: 1 day (during colonoscopy)
measure: Withdrawal time
timeFrame: 1 day (during colonoscopy)
measure: Polyp detection rate
timeFrame: Within 30 days from colonoscopy date
measure: Patients characteristics questionnaire
timeFrame: 1 day (immediately before colonoscopy)
Locations:
city: Coimbra
country: Portugal
facility: Portuguese Oncology Institute - Coimbra
Study officials:
affiliation: Portuguese Oncology Institute, Coimbra
name: Miguel Areia, PhD
role: STUDY_DIRECTOR
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