Planning Clinical Trial Programme for Bowel Cleansing Medicinal Products (Review)

INTRODUCTION. Colon cleansing plays an essential role in preparation for diagnostic procedures and surgical interventions. One of the key factors ensuring high-quality colon cleansing is the correct choice of a medicinal product that affects the intestinal contents and removes them from the body. Planning and conducting clinical trials for new effective colon cleansing medicines that are well-tolerated and have a favourable safety profile is an urgent task for health care. Currently, there are no regulatory documents on planning a clinical trial programme for colon cleansing medicinal products in the Russian Federation or the Eurasian Economic Union.

AIM. This study aimed to prepare recommendations for planning a clinical trial programme for bowel cleansing medicinal products.

DISCUSSION. Main provisions of the Guidelines of European Medicines Agency (EMA) were analysed for new medicinal products used in chronic constipation. The Guidelines define specific conditions for pharmacological studies and confirmatory clinical trials (regarding choice of design, study population, criteria for assessing efficacy and safety), as well as specific requirements for clinical trials in paediatric and elderly patients. Particular features of clinical trials for bowel cleansing medicines include patients with no comorbidities other than bowel disease; confirmatory clinical trials designed as randomised, active-control studies in parallel groups; safety assessment for a single-use medicinal product; long-term safety studies not required.

CONCLUSIONS. The main research models described in EMA Guidelines on clinical trials of bowel cleansing medicinal products enable a reliable assessment of safety and efficacy of the above medicines and can serve to prepare guidelines on clinical trial planning for bowel cleansing medicinal products.

1. Kanner EV, Maximov ML, Ermolaeva AS, et al. Modern and promising ways of bowel preparation for instrumental research. Ambulatory Surgery (Russia). 2021;18(1):91–102 (In Russ.). https://doi.org/10.21518/1995-1477-2021-18-1-91-102

2. Kashin SV, Nekhaykova NV, Zavyalov DV, et al. The colorectal cancer screening: The current global situation and the main standards for the quality of screening colonoscopy recommended by the European Society of Gastrointestinal Endoscopy (ESGE). Russian Journal of Evidence-based Gastroenterology. 2017;(4):32–52 (In Russ.). https://doi.org/10.17116/dokgastro20176432-52

3. Kaprin AD, Starinsky VV, Shakhzadova AO, eds. Malignant neoplasms in Russia in 2023 (morbidity and mortality). Moscow: P.A. Herzen Moscow Oncology Research Institute — branch of the National Medical Research Center of Radiology of the Ministry of Health of the Russian Federation; 2024 (In Russ.). https://oncology-association.ru/wp-content/uploads/2024/08/zis-2023-elektronnaya-versiya.pdf

4. Tonini V, Zanni M. Why is early detection of colon cancer still not possible in 2023? World J Gastroenterol. 2024;30(3):211–24. https://doi.org/10.3748/wjg.v30.i3.211

5. Bretthauer M, Løberg M, Wieszczy P, et al. Effect of colonoscopy screening on risks of colorectal cancer and related death. N Engl J Med. 2022;387(17):1547–56. https://doi.org/10.1056/nejmoa2208375

6. Kashin SV, Nikonov EL, Nekhaykova NV, et al. Standards of quality colonoscopy (Guidelines for doctors). Russian Journal of Evidence-based Gastroenterology. 2019;8(1–2):3–32 (In Russ.). https://doi.org/10.17116/dokgastro20198012003

7. Galyaev AV, Mtvralashvili DA, Arkhipova OV, et al. The use of enteral nutrition in bowel cleansing before colonoscopy. Koloproktologia. 2018;(4):25–30 (In Russ.). https://doi.org/10.33878/2073-7556-2018-0-4-25-30

8. Zhuravleva MV, Serebrova SYu, Ponomarenko TM, et al. Clinical pharmacology of drugs for bowel cleansing prior to any diagnostic and/or surgical procedures requiring clean bowel: analysis of efficacy and safety parameters. Russian Journal of Evidence-based Gastroenterology. 2020;9(1):50–67 (In Russ.). https://doi.org/10.17116/dokgastro2020901150

9. Shcherbakov PL, Parfenov AI, Albulova EV. New schemes of preparation of the intestine for colonoscopy. Lechaschi Vrach. 2014;(11):75 (In Russ.). EDN: TEWQZD

10. Soloviev MV, Lukyanchuk RM, Gordienko AV, Sorokin NV. Historical, modern and perspective agents and methods of preparation of the intestine for special exams. Farmateka. 2018;(13):8–16 (In Russ.). https://doi.org/10.18565/pharmateca.2018.13.8-16

11. Hagen R, Nguyen MTT, Anderson JC, et al. Navigating bowel preparation for colonoscopy: A comprehensive overview. J Clin Gastroenterol. 2025;59(4):285–97. https://doi.org/10.1097/mcg.0000000000002124

12. Hassan C, East J, Radaelli F, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Update 2019. Endoscopy. 2019;51(8):775–94. https://doi.org/10.1055/a-0959-0505

13. Veselov VV, Sidorov AV, Vasiluk VB, et al. Low-volume PEG plus ascorbic acid as bowel preparation for colonoscopy using morning-only dosing regimen compared to standard split-dosing: Multicenter single-blind randomized parallel-group controlled study. Koloproktologia. 2017;(2S):5–18 (In Russ.). https://doi.org/10.33878/2073-7556-2017-0-2S-5-18

14. Kashin SV, Nekhaykova NV, Vidyaeva NS, Belova AN. The fundamental principles of the European Society of Gastrointestinal Endoscopy guidelines on bowel preparation for screening colonoscopy. Russian Journal of Evidence-based Gastroenterology. 2017;6(3):36–50 (In Russ.). https://doi.org/10.17116/dokgastro20176336-50

15. Singal AK, Rosman AS, Post JB, et al. The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol. Aliment Pharmacol Ther. 2008;27(1):41–7. https://doi.org/10.1111/j.1365-2036.2007.03558.x

16. Kannankeril P, Roden DM, Darbar D. Drug-induced long QT syndrome. Pharmacol Rev. 2010;62(4):760–81. https://doi.org/10.1124/pr.110.003723

17. Casais MN, Rosa-Diez G, Pérez S, et al. Hyperphosphatemia after sodium phosphate laxatives in low risk patients: Prospective study. World J Gastroenterol. 2009;15(47):5960–5. https://doi.org/10.3748/wjg.15.5960

18. Patel V, Nicar M, Emmett M, et al. Intestinal and renal effects of low-volume phosphate and sulfate cathartic solutions designed for cleansing the colon: pathophysiological studies in five normal subjects. Am J Gastroenterol. 2009;104(4):953–65. https://doi.org/10.1038/ajg.2008.124

19. Pozdeev IV, Belyayev MV, Shengeliya EI, Parfenyuk AV. Effective bowel cleansing for colonoscopy: Picoprep use. Koloproktologia. 2018;(4):45–9 (In Russ.). https://doi.org/10.33878/2073-7556-2018-0-4-45-49

20. Saltzman JR, Cash BD, Pasha SF, et al. Bowel preparation before colonoscopy. Gastrointest Endosc. 2015;81(4):781– 94. https://doi.org/10.1016/j.gie.2014.09.048

21. Matro R, Shnitser A, Spodik M, et al. Efficacy of morning-only compared with split-dose polyethylene glycol electrolyte solution for afternoon colonoscopy: A randomized controlled single-blind study. Am J Gastroenterol. 2010;105(9):1954–61. https://doi.org/10.1038/ajg.2010.160

22. Hunter A, Mamula P. Bowel preparation for pediatric colonoscopy procedures. J Pediatr Gastroenterol Nutr. 2010;51(3):254–61. https://doi.org/10.1097/mpg.0b013e3181eb6a1c

23. Ivanova EV, Anikina NYu, Tikhomirova EV, et al. Bowel preparation using reduced dosage of polyethylene glycol in combination with stimulant type laxatives. Lechaschi Vrach. 2015;(9):68 (In Russ.). EDN: ULSTYR

24. Yoon JY, Kim HG, Cho YS, et al. 1 L-versus 2 L-polyethylene glycol with ascorbic acid for bowel preparation in elderly patients: A randomized multicenter study. Surg Endosc. 2022;36(8):5724–33. https://doi.org/10.1007/s00464-021-08947-4

25. DeMicco MP, Clayton LB, Pilot J, et al. Novel 1 L polyethylene glycol-based bowel preparation NER1006 for overall and right-sided colon cleansing: A randomized controlled phase 3 trial versus trisulfate. Gastrointest Endosc. 2018;87(3):677–87. https://doi.org/10.1016/j.gie.2017.07.047

26. Di Palma JA, Bhandari R, Cleveland M, et al. A safety and efficacy comparison of a new sulfate-based tablet bowel preparation versus a PEG and ascorbate comparator in adult subjects undergoing colonoscopy. Am J Gastroenterol. 2021;116(2):319–28. https://doi.org/10.14309/ajg.0000000000001020

27. Kim JH, Park YE, Kim TO. Comparison of the efficacy and safety between oral sulfate tablet and polyethylene glycol for bowel preparation before colonoscopy according to age. Medicine (Baltimore). 2022;101(27):e29884. https://doi.org/10.1097/md.0000000000029884

28. Pyrkh AV, Ivinskaya OV, Shirokov II. Application of the combination of polyethyleneglycol and symeticone preparations in the preparation for the route diagnostic and medical colonoscopy. Consilium Medicum. 2017;(2):52–4 (In Russ.). EDN: ZTUTER

29. Lee SE, Oh DJ, Nam JH, et al. Taking oral sulfate tablets with simethicone for bowel preparation leads to higher adenoma detection rate than polyethylene glycol: A propensity score analysis. Dig Dis Sci. 2023;68(3):867–76. https://doi.org/10.1007/s10620-022-07611-8

30. Jung Y, Kim HG, Yang D-H, et al. Efficacy of oral sulfate tablet and 2 L-polyethylene glycol with ascorbic acid for bowel preparation: A prospective randomized KASID multicenter trial. J Korean Med Sci. 2024;39(48):e301. https://doi.org/lO.3346/jkms.2O24.39.e3O1

31. Kang HS, Na SY, Yoon JY, et al. Efficacy, tolerability, and safety of oral sulfate tablet versus 2 L-polyethylene glycol/ascorbate for bowel preparation in older patients: Prospective, multicenter, investigator single-blinded, randomized study. J Gastroenterol. 2024;59(5):402–10. https://doi.org/10.1007/s00535-024-02089-9

32. Bhandari R, Goldstein M, Mishkin DS, et al. Comparison of a novel, flavor-optimized, polyethylene glycol and sulfate bowel preparation with oral sulfate solution in adults undergoing colonoscopy. J Clin Gastroenterol. 2023;57(9):920– 7. https://doi.org/10.1097/mcg.0000000000001894

33. Knyazev MV, Shcherbakov PL, Parfenov AI, Albulova EV. Colon cleansing before colonoscopy: Balance of effectiveness, safety and accessability of the medications. Endoscopic Surgery. 2015;21(3):30–6 (In Russ.). https://doi.org/10.17116/endoskop201521330-36

34. Malichenko VS. Harmonization of healthcare technologies regulation in frame of regional integration processes. Remedium. 2022;(1):75–81 (In Russ.). https://doi.org/10.32687/1561-5936-2022-26-1-75-81

35. Taube AА. Some aspects of legal regulation of circulation of medical products for medical use in the EU and the EAEU. Medical & Pharmaceutical Journal “Pulse”. 2019;21(10):12–9 (In Russ.). https://doi.org/10.26787/nydha-2686-6838-2019-21-10-12-19

36. Johnson DA, Barkun AN, Cohen LB, et al. Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the U.S. multi-society task force on colorectal cancer. Gastrointest Endosc. 2014;80(4):543–62. https://doi.org/10.1016/j.gie.2014.08.002

37. Shreder OV, Goryachev DV, Merkulov VA. Basic principles for calculating the required number of participants in clinical trials. Part 1. Common approaches (review). Regulatory Research and Medicine Evaluation. 2024;14(3):338–50 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-3-338-350

38. Kastenberg D, Bertiger G, Brogadir S. Bowel preparation quality scales for colonoscopy. World J Gastroenterol. 2018; 24(26):2833–43. https://doi.org/10.3748/wjg.v24.i26.2833

39. Calderwood A, Jacobson B. Comprehensive validation of the Boston Bowel Preparation Scale. Gastrointest Endosc. 2010;72(4):686–92. https://doi.org/10.1016/j.gie.2010.06.068

40. Lorenzo-Zúñiga V, Moreno-de-Vega V, Boix J. Preparation for colonoscopy: Types of scales and cleaning products. Rev Esp Enferm Dig. 2012;104(8):426–31 (In Spanish). https://doi.org/10.4321/s1130-01082012000800006

41. Cohen LB. Advances in bowel preparation for colonoscopy. Gastrointest Endosc Clin N Am. 2015;25(2):183–97. https://doi.org/10.1016/j.giec.2014.11.003

42. Parmar R, Martel M, Rostom A, Barkun AN. Validated scales for colon cleansing: A systematic review. Am J Gastroenterol. 2016;111(2):197–204. https://doi.org/10.1038/ajg.2015.417

43. Vologzhanina LG, Igumnova OA, Petukhova IV, Sannikov PK. Effective bowel cleansing for screening colonoscopy. Koloproktologia. 2020;19(3):65–71 (In Russ.). https://doi.org/10.33878/2073-7556-2020-19-3-65-71

44. Fedorov ED, Veselov VV, Kashin SV, et al. Assessment of bowel preparation using low-volume sulphate-based preparations in comparison with macrogols: A multicenter, randomized, comparative clinical study of the 3rd phase. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(2):60–75 (In Russ.). https://doi.org/10.22416/1382-4376-2019-29-2-60-75