Effect of Adding Simethicone to Split-dose Polyethylene Glycol for Bowel Preparation in a Screening Colonoscopy Setting

Colonic Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03816774
• Other study ID #: PortugueseOIC 003
• Status: Completed
• Phase: N/A
• Start date: June 15, 2019
• Est. completion date: September 17, 2022

Study information

• Verified date: October 2022
• Source: Portuguese Oncology Institute, Coimbra
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 412
• Est. completion date: September 17, 2022
• Est. primary completion date: September 17, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 74 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colo-rectal Cancer
• Colonic Neoplasms
• Rectal Neoplasms

Intervention

Drug:
• PEG split-dose and simethicone
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

Locations

Country	Name	City	State
Portugal	Portuguese Oncology Institute - Coimbra	Coimbra

Sponsors (1)

Lead Sponsor	Collaborator
Portuguese Oncology Institute, Coimbra

Country where clinical trial is conducted

Portugal, 

References & Publications (14)

Bai Y, Fang J, Zhao SB, Wang D, Li YQ, Shi RH, Sun ZQ, Sun MJ, Ji F, Si JM, Li ZS. Impact of preprocedure simethicone on adenoma detection rate during colonoscopy: a multicenter, endoscopist-blinded randomized controlled trial. Endoscopy. 2018 Feb;50(2):128-136. doi: 10.1055/s-0043-119213. Epub 2017 Oct 6. — View Citation

de Leone A, Tamayo D, Fiori G, Ravizza D, Trovato C, De Roberto G, Fazzini L, Dal Fante M, Crosta C. Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy. World J Gastrointest Endosc. 2013 Sep 16;5(9):433-9. doi: 10.4253/wjge.v5.i9.433. — View Citation

Despacho n.o 8254/2017. Diário da República, 2.a série - N.o 183 - 21 de setembro de 2017. 2017;20788-9.

Hassan C, Bretthauer M, Kaminski MF, Polkowski M, Rembacken B, Saunders B, Benamouzig R, Holme O, Green S, Kuiper T, Marmo R, Omar M, Petruzziello L, Spada C, Zullo A, Dumonceau JM; European Society of Gastrointestinal Endoscopy. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2013;45(2):142-50. doi: 10.1055/s-0032-1326186. Epub 2013 Jan 18. — View Citation

Hassan C, Quintero E, Dumonceau JM, Regula J, Brandão C, Chaussade S, Dekker E, Dinis-Ribeiro M, Ferlitsch M, Gimeno-García A, Hazewinkel Y, Jover R, Kalager M, Loberg M, Pox C, Rembacken B, Lieberman D; European Society of Gastrointestinal Endoscopy. Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2013 Oct;45(10):842-51. doi: 10.1055/s-0033-1344548. Epub 2013 Sep 12. — View Citation

Kaminski MF, Thomas-Gibson S, Bugajski M, Bretthauer M, Rees CJ, Dekker E, Hoff G, Jover R, Suchanek S, Ferlitsch M, Anderson J, Roesch T, Hultcranz R, Racz I, Kuipers EJ, Garborg K, East JE, Rupinski M, Seip B, Bennett C, Senore C, Minozzi S, Bisschops R, Domagk D, Valori R, Spada C, Hassan C, Dinis-Ribeiro M, Rutter MD. Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) quality improvement initiative. United European Gastroenterol J. 2017 Apr;5(3):309-334. doi: 10.1177/2050640617700014. Epub 2017 Mar 16. Review. — View Citation

Lazzaroni M, Petrillo M, Desideri S, Bianchi Porro G. Efficacy and tolerability of polyethylene glycol-electrolyte lavage solution with and without simethicone in the preparation of patients with inflammatory bowel disease for colonoscopy. Aliment Pharmacol Ther. 1993 Dec;7(6):655-9. — View Citation

Matro R, Tupchong K, Daskalakis C, Gordon V, Katz L, Kastenberg D. The effect on colon visualization during colonoscopy of the addition of simethicone to polyethylene glycol-electrolyte solution: a randomized single-blind study. Clin Transl Gastroenterol. 2012 Nov 29;3:e26. doi: 10.1038/ctg.2012.16. — View Citation

Pan P, Zhao SB, Li BH, Meng QQ, Yao J, Wang D, Li ZS, Bai Y. Effect of supplemental simethicone for bowel preparation on adenoma detection during colonoscopy: A meta-analysis of randomized controlled trials. J Gastroenterol Hepatol. 2019 Feb;34(2):314-320. doi: 10.1111/jgh.14401. Epub 2018 Aug 27. — View Citation

Parmar R, Martel M, Rostom A, Barkun AN. Validated Scales for Colon Cleansing: A Systematic Review. Am J Gastroenterol. 2016 Feb;111(2):197-204; quiz 205. doi: 10.1038/ajg.2015.417. Epub 2016 Jan 19. Review. — View Citation

Wu L, Cao Y, Liao C, Huang J, Gao F. Systematic review and meta-analysis of randomized controlled trials of Simethicone for gastrointestinal endoscopic visibility. Scand J Gastroenterol. 2011 Feb;46(2):227-35. doi: 10.3109/00365521.2010.525714. Epub 2010 Oct 26. Review. — View Citation

Yeh JH, Hsu MH, Tseng CM, Chen TH, Huang RY, Lee CT, Lin CW, Wang WL. The benefit of adding oral simethicone in bowel preparation regimen for the detection of colon adenoma: A systematic review and meta-analysis. J Gastroenterol Hepatol. 2019 May;34(5):830-836. doi: 10.1111/jgh.14508. Epub 2018 Nov 4. — View Citation

Yoo IK, Jeen YT, Kang SH, Lee JH, Kim SH, Lee JM, Choi HS, Kim ES, Keum B, Chun HJ, Lee HS, Kim CD. Improving of bowel cleansing effect for polyethylene glycol with ascorbic acid using simethicone: A randomized controlled trial. Medicine (Baltimore). 2016 Jul;95(28):e4163. doi: 10.1097/MD.0000000000004163. — View Citation

Zhang S, Zheng D, Wang J, Wu J, Lei P, Luo Q, Wang L, Zhang B, Wang H, Cui Y, Chen M. Simethicone improves bowel cleansing with low-volume polyethylene glycol: a multicenter randomized trial. Endoscopy. 2018 Apr;50(4):412-422. doi: 10.1055/s-0043-121337. Epub 2017 Nov 13. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Degree of mucosal bubble	Degree of mucosal bubble in each colonic segment (ascendent, transverse, descendent) 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).	1 day (during colonoscopy)
Other	Withdrawal time	Time spent on withdrawal of the endoscope from cecum to anal canal and inspection of the entire bowel mucosa at negative (no biopsy or therapy) colonoscopy, presented in minutes.	1 day (during colonoscopy)
Other	Polyp detection rate	Colonoscopies with a detection of at least one polyp, presented as percentage.	Within 30 days from colonoscopy date
Other	Patients characteristics questionnaire	Evaluate, using proper data collecting sheet, patient relevant data (age, gender, chronic medication, risk factors for inappropriate preparation)	1 day (immediately before colonoscopy)
Primary	Adequate bowel preparation rate	Total BBPS =6 and =2 in each segment (ascendent, transverse, descendent), presented as percentage.	1 day (during colonoscopy)
Secondary	Adenoma detection rate	Colonoscopies with at least one adenoma identified, presented as percentage.	Within 30 days from colonoscopy date
Secondary	Cecal intubation rate	Photo documentation of the cecum is a mark for effective total colonoscopy, presented as percentage.	1 day (during colonoscopy)
Secondary	Compliance to the bowel cleansing regimen	Patient assessment, by written questionnaire, of compliance of the bowel cleansing regimen.	1 day (immediately before colonoscopy)
Secondary	Tolerability to the bowel cleansing regimen:questionnaire	Patient assessment, by written questionnaire, of side effects of the bowel cleansing regimen.	1 day (immediately before colonoscopy)