Effect of Adding Simethicone to Split-dose Polyethylene Glycol for Bowel Preparation in a Screening Colonoscopy Setting
Condition: Colo-rectal Cancer; Colonic Neoplasms
MeSH terms: Rectal Neoplasms; Colonic Neoplasms
Study type: Interventional

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.
    

Intervention name(s): PEG split-dose and simethicone
Intervention type(s): Drug
Intervention description(s): Patients in active comparator arm are instructed to take 250mg simethicone pill 15 minutes before PEG dose on the previous evening plus 250mg simethicone pill 15 minutes before PEG dose ending 3 hours before colonoscopy
Other intervention name(s): Aero-OM
Intervention MeSH terms: Simethicone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Care Provider)
Primary purpose: Diagnostic
Keywords: screening colonoscopy; colo-rectal cancer; simethicone; split-dose polyethylene glycol; adequate bowel preparation