Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis

Colon Cancer Clinical Trial

— PrepDial  

Official title:

Comparison of Low-volume Versus High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis: a Randomized Non-inferiority Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04709770
• Other study ID #: Policlinic Hospital 7
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: February 1, 2021
• Est. completion date: March 1, 2022

Study information

• Verified date: January 2021
• Source: University of Bari
• Contact: Alfredo Di Leo, MD PhD
• Phone: +39 080 5592925
• Email: alfredo.dileo[@]uniba.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Current American Society for Gastrointestinal Endoscopy (ASGE) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines recommend a split regimen of high-volume (4-liter polyethylene glycol-based preparation) or low-volume (2-liter polyethylene glycol-based solutions or sodium picosulphate plus magnesium citrate) formulations for routine bowel preparation. Some concerns have been raised about the use of oral bowel-cleansing agents in people receiving hemodialysis due to the possibility of secondary intravascular depletion. There is a risk for thrombosis of dialysis access in case of hypotension. The association of hemodialysis treatment and the use of bowel preparations may induce severe hypovolaemia. Finally, the 4-liter intake with high-volume preparations may cause fluid overload in anuric patients. The aim of our study will be to assess in a randomized trial the non-inferiority of a low-volume versus a high-volume polyethylene glycol-based bowel preparation for adequate bowel cleansing in people receiving hemodialysis (primary end-point). We will also compare the low-volume versus the high-volume preparation for other endoscopic and nephrologic relevant clinical outcomes (secondary end-points).

Description:

Study design: This will be a multicentre, outcome assessor-blinded, parallel-arm, centrally randomized, non-inferiority trial. Randomization will be performed centrally by the coordinating center. Consecutive inpatients and outpatients on hemodialysis with an indication to undergo colonoscopy (positive fecal occult blood test or fecal immunochemical test, signs or symptoms of colorectal disease, colorectal cancer screening, colorectal cancer surveillance, inflammatory bowel diseases, or inclusion in kidney transplantation waiting list) will be screened for inclusion in the trial. At enrolment visit, eligible subjects will be allocated to either the low-volume or high-volume bowel preparation group (ratio 1:1). Participants in the low-volume group will receive the formulation of 2-liters polyethylene glycol with citrate and simethicone (Clensia, Alfasigma S.p.A., Milan, Italy), while those in the high-volume arm will receive 4-liters polyethylene glycol with simethicone (Selg Esse, Alfasigma S.p.A., Milan, Italy). Participants in both groups will be prescribed a low residue diet for 3 days before colonoscopy and will be instructed to take the bowel cleansing agents as split dose, taking the first half of solution the evening before the endoscopic examination and the second in the morning of the day of the procedure. To improve compliance, participants will also receive a booklet in plain language to explain the details of low residue diet and modality of bowel preparation intake. All endoscopic examinations will be scheduled on days free from dialysis sessions between 2 and 5 hours after the end of the administration of the last dose of preparation. On the day of the colonoscopy, all participants will fill in a questionnaire to measure participants' compliance, tolerability, and willingness to repeat the preparation they have been allocated to. Participants will be aware of the bowel preparation they received. On the opposite, endoscopists and nephrologists measuring primary and secondary outcomes (i.e. outcome assessors) will be blinded to the arm each subject has been allocated to and instructed to avoid any discussion with participants that could reveal the type of bowel cleansing agent. Recruitment will last 12 months and follow-up will be completed 1 month after the last participant undergoes colonoscopy. Before randomization and during the one-month follow-up, participants will receive (in a non-randomized fashion) all relevant co-interventions (e.g. iron, lipid-lowering agents, bone disease agents, antihypertensive agents, etc.), which are peculiar of standard hemodialysis treatment, as per their usual attending physician's practice to achieve and maintain standard hemodialysis clinical performance measures. At the time of enrolment and colonoscopy scheduled simple trial follow-up visits will be performed. All clinical events following the endoscopic procedure will be measured during the one-month follow-up period.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 264
• Est. completion date: March 1, 2022
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• prevalent end stage kidney disease on hemodialysis people (on hemodialysis for =6 months; either hemodialysis or hemofiltration or hemodiafiltration, received for at least 3 times/week for a minimum duration of 4 hours per treatment session for a minimum of 12 hours/week, according to standard practice for quality hemodialysis in Italy);
• inpatients and outpatients with an indication to colonoscopy (e.g. positive fecal occult blood test or fecal immunochemical test, signs or symptoms of colorectal disease, colorectal cancer screening, colorectal cancer surveillance, inflammatory bowel diseases, or inclusion in kidney transplantation waiting list);
• signature of written informed consent.

Exclusion Criteria:

• end stage kidney disease not on hemodialysis (eg. peritoneal dialysis or kidney transplantation);
• previous kidney transplantation;
• need for colonoscopy in emergency;
• previous colorectal surgery;
• contraindications to colonoscopy in the opinion of the managing physician;
• pregnancy or breastfeeding assessed by dedicated pregnancy tests;
• known or suspected hypersensitivity to any components of preparations.
• gastrointestinal perforation;
• toxic megacolon;
• inflammatory bowel disease (such as rectal ulcerative colitis, Crohn's disease) in severe acute phase;
• occlusive, sub-occlusive or stenotic forms of the intestine, gastric stasis, dynamic ileus, paralytic ileus;
• severe state of dehydration;
• phenylketonuria (due to the presence of aspartame);
• glucose-6-phosphate dehydrogenase deficiency;
• severe heart failure: New York Heart Association (NYHA) class III-IV;
• significant alterations of electrolytes, according to the physician's judgment;
• participation in a clinical study in which an experimental drug was administered within 30 days or 5 half-lives before the study drug.

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Colon Cancer
• Colon Polyp
• Dialysis; Complications
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• 2-liters polyethylene glycol with citrate and simethicone
Low-volume polyethylene glycol-based bowel cleansing agent for colonoscopy.
• 4-liters polyethylene glycol with simethicone
High-volume polyethylene glycol-based bowel cleansing agent for colonoscopy.

Dietary Supplement:
• Low-residue diet
Diet before colonoscopy.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Alfredo Di Leo	Alfasigma S.p.A.

References & Publications (21)

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ASGE Standards of Practice Committee, Saltzman JR, Cash BD, Pasha SF, Early DS, Muthusamy VR, Khashab MA, Chathadi KV, Fanelli RD, Chandrasekhara V, Lightdale JR, Fonkalsrud L, Shergill AK, Hwang JH, Decker GA, Jue TL, Sharaf R, Fisher DA, Evans JA, Foley K, Shaukat A, Eloubeidi MA, Faulx AL, Wang A, Acosta RD. Bowel preparation before colonoscopy. Gastrointest Endosc. 2015 Apr;81(4):781-94. doi: 10.1016/j.gie.2014.09.048. Epub 2015 Jan 14. — View Citation

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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, Fuccio L, Bruno M, Pagano N, Spada C, Carrara S, Giordanino C, Rondonotti E, Curcio G, Dulbecco P, Fabbri C, Della Casa D, Maiero S, Simone A, Iacopini F, Feliciangeli G, Manes G, Rinaldi A, Zullo A, Rogai F, Repici A. A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy. Clin Gastroenterol Hepatol. 2012 May;10(5):501-6. doi: 10.1016/j.cgh.2011.12.037. Epub 2012 Jan 10. — View Citation

Johnson DA, Barkun AN, Cohen LB, Dominitz JA, Kaltenbach T, Martel M, Robertson DJ, Boland CR, Giardello FM, Lieberman DA, Levin TR, Rex DK; US Multi-Society Task Force on Colorectal Cancer. Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the US multi-society task force on colorectal cancer. Gastroenterology. 2014 Oct;147(4):903-24. doi: 10.1053/j.gastro.2014.07.002. Review. — View Citation

Kang X, Zhao L, Zhu Z, Leung F, Wang L, Wang X, Luo H, Zhang L, Dong T, Li P, Chen Z, Ren G, Jia H, Guo X, Pan Y, Guo X, Fan D. Same-Day Single Dose of 2 Liter Polyethylene Glycol is Not Inferior to The Standard Bowel Preparation Regimen in Low-Risk Patients: A Randomized, Controlled Trial. Am J Gastroenterol. 2018 Apr;113(4):601-610. doi: 10.1038/ajg.2018.25. Epub 2018 Mar 13. — View Citation

Komaki Y, Komaki F, Micic D, Ido A, Sakuraba A. Risk of Colorectal Cancer in Chronic Kidney Disease: A Systematic Review and Meta-Analysis. J Clin Gastroenterol. 2018 Oct;52(9):796-804. doi: 10.1097/MCG.0000000000000880. — View Citation

Kump P, Hassan C, Spada C, Brownstone E, Datz C, Haefner M, Renner F, Schoefl R, Schreiber F. Efficacy and safety of a new low-volume PEG with citrate and simethicone bowel preparation for colonoscopy (Clensia): a multicenter randomized observer-blind clinical trial vs. a low-volume PEG with ascorbic acid (PEG-ASC). Endosc Int Open. 2018 Aug;6(8):E907-E913. doi: 10.1055/a-0624-2266. Epub 2018 Aug 1. — View Citation

Lai EJ, Calderwood AH, Doros G, Fix OK, Jacobson BC. The Boston bowel preparation scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc. 2009 Mar;69(3 Pt 2):620-5. doi: 10.1016/j.gie.2008.05.057. Epub 2009 Jan 10. — View Citation

Lee JM, Keum B, Yoo IK, Kim SH, Choi HS, Kim ES, Seo YS, Jeen YT, Chun HJ, Lee HS, Um SH, Kim CD, Kim MG, Jo SK. Polyethylene glycol plus ascorbic acid for bowel preparation in chronic kidney disease. Medicine (Baltimore). 2016 Sep;95(36):e4755. doi: 10.1 — View Citation

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Mahmood S, Farooqui SM, Madhoun MF. Predictors of inadequate bowel preparation for colonoscopy: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018 Aug;30(8):819-826. doi: 10.1097/MEG.0000000000001175. Review. — View Citation

Rex DK, Imperiale TF, Latinovich DR, Bratcher LL. Impact of bowel preparation on efficiency and cost of colonoscopy. Am J Gastroenterol. 2002 Jul;97(7):1696-700. — View Citation

Spada C, Cesaro P, Bazzoli F, Saracco GM, Cipolletta L, Buri L, Crosta C, Petruzziello L, Ceroni L, Fuccio L, Giordanino C, Elia C, Rotondano G, Bianco MA, Simeth C, Consalvo D, De Roberto G, Fiori G, Campanale M, Costamagna G. Evaluation of Clensia(®), a new low-volume PEG bowel preparation in colonoscopy: Multicentre randomized controlled trial versus 4L PEG. Dig Liver Dis. 2017 Jun;49(6):651-656. doi: 10.1016/j.dld.2017.01.167. Epub 2017 Feb 3. — View Citation

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adequate bowel preparation	Proportion of participants with Boston Bowel Preparation Scale =6 with each segmental score =2	During colonoscopy
Secondary	Adenoma detection rate	Proportion of patients with at least one adenoma	During colonoscopy
Secondary	Cecal intubation rate	Proportion of endoscopic examinations reaching the cecum	During colonoscopy
Secondary	Participants' compliance	Proportion of participants with intake of at least 75 percent of the bowel preparation	During colonoscopy
Secondary	Participants' tolerability	Proportion of participants presenting nausea, bloating, vomiting, abdominal pain, and/or anal irritation	During colonoscopy
Secondary	Willingness to repeat the preparation	Proportion of participants willing to use the same bowel preparation for future examinations	During colonoscopy
Secondary	Adverse events	Proportion of participants with any adverse event occurred during the intake of bowel preparation	During colonoscopy and the first hemodialysis session following colonoscopy
Secondary	All-cause hospitalization	Proportion of participants hospitalized after bowel preparation intake for any cause	Within a 30-day period
Secondary	All-cause mortality	Proportion of participants who died after bowel preparation intake for any cause	Within a 30-day period
Secondary	Emergency hemodialysis sessions	Proportion of participants needing additional hemodialysis sessions	Within a 30-day period
Secondary	Cardiovascular events	Proportion of participants with cardiovascular events (i.e. nonfatal myocardial infarction, acute coronary syndrome, and/or heart failure)	Within a 30-day period
Secondary	Interdialytic body weight gain	Mean increase in body weight from the hemodialysis session preceding the intake of bowel preparation to the one following the colonoscopy	During the hemodialysis session preceding and the one following the intake of bowel preparation
Secondary	Variations in serum-electrolyte levels	Mean variation in serum-electrolyte levels between the hemodialysis session preceding and following the intake of bowel preparation	During the hemodialysis session preceding and the one following the intake of bowel preparation
Secondary	Systolic blood pressure	Mean variation in systolic blood pressure between the hemodialysis session preceding and following the intake of bowel preparation	During the hemodialysis session preceding and the one following the intake of bowel preparation
Secondary	Diastolic blood pressure	Mean variation in diastolic blood pressure between the hemodialysis session preceding and following the intake of bowel preparation	During the hemodialysis session preceding and the one following the intake of bowel preparation
Secondary	Blood flow on dialysis	Mean variation in blood flow on dialysis between the hemodialysis session preceding and following the intake of bowel preparation	During the hemodialysis session preceding and the one following the intake of bowel preparation