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

Phase 4
Conditions
Colon Polyp
Chronic Kidney Diseases
Colon Cancer
Dialysis; Complications
Interventions
Registration Number
NCT04709770
Lead Sponsor
Alfredo Di Leo
Brief 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).

Detailed 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 & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
264
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Low-volume preparation2-liters polyethylene glycol with citrate and simethiconeLow-volume preparation of 2-liters polyethylene glycol with citrate and simethicone. This formulation includes 4 large (A) and 4 small (B) sachets; the components of 2 sachets A and 2 sachets B are mixed in 1 liter of water. Each sachet A contains: * polyethylene glycol (4000) 52.50 g; * simethicone 0.08 g; * sodium sulphate anhydrous 3.75 g. Each sachet B contains: * sodium citrate 1.863 g; * anhydrous citric acid 0.813 g; * sodium chloride 0.73 g; * potassium chloride: 0.37 g; * acesulfame potassium 0.13 g. Participants will drink the first liter of preparation at 19.00 p.m. on the day before the colonoscopy, at a rate of 250 ml every 15 minutes, followed by 500 ml of clear liquids. The second liter of preparation will be administered at 7.00 a.m. on the day of the colonoscopy, at a rate of 250 ml every 15 minutes, followed by 500 ml of clear liquids.
Low-volume preparationLow-residue dietLow-volume preparation of 2-liters polyethylene glycol with citrate and simethicone. This formulation includes 4 large (A) and 4 small (B) sachets; the components of 2 sachets A and 2 sachets B are mixed in 1 liter of water. Each sachet A contains: * polyethylene glycol (4000) 52.50 g; * simethicone 0.08 g; * sodium sulphate anhydrous 3.75 g. Each sachet B contains: * sodium citrate 1.863 g; * anhydrous citric acid 0.813 g; * sodium chloride 0.73 g; * potassium chloride: 0.37 g; * acesulfame potassium 0.13 g. Participants will drink the first liter of preparation at 19.00 p.m. on the day before the colonoscopy, at a rate of 250 ml every 15 minutes, followed by 500 ml of clear liquids. The second liter of preparation will be administered at 7.00 a.m. on the day of the colonoscopy, at a rate of 250 ml every 15 minutes, followed by 500 ml of clear liquids.
High-volume preparation4-liters polyethylene glycol with simethiconeHigh-volume preparation with 4-liters polyethyleneglycol with simethicone. This formulation includes 4 sachets, each dissolved in 1 liter of water. Each sachet contains: * polyethylene glycol (4000) 58.30 g; * simethicone 0.08 g; * sodium sulphate anhydrous 5.68 g; * sodium bicarbonate 1.68 g; * sodium chloride 1.46 g; * potassium chloride 0.74 g. Participants will drink the first 2 liters of preparation at 19.00 p.m. on the day before colonoscopy, at a rate of 250 ml every 15 minutes. The remaining 2 liters of preparation will be administered at 6.00 a.m. on the day of the endoscopic procedure, at a rate of 250 ml every 15 minutes.
High-volume preparationLow-residue dietHigh-volume preparation with 4-liters polyethyleneglycol with simethicone. This formulation includes 4 sachets, each dissolved in 1 liter of water. Each sachet contains: * polyethylene glycol (4000) 58.30 g; * simethicone 0.08 g; * sodium sulphate anhydrous 5.68 g; * sodium bicarbonate 1.68 g; * sodium chloride 1.46 g; * potassium chloride 0.74 g. Participants will drink the first 2 liters of preparation at 19.00 p.m. on the day before colonoscopy, at a rate of 250 ml every 15 minutes. The remaining 2 liters of preparation will be administered at 6.00 a.m. on the day of the endoscopic procedure, at a rate of 250 ml every 15 minutes.
Primary Outcome Measures
NameTimeMethod
Adequate bowel preparationDuring colonoscopy

Proportion of participants with Boston Bowel Preparation Scale ≥6 with each segmental score ≥2

Secondary Outcome Measures
NameTimeMethod
Emergency hemodialysis sessionsWithin a 30-day period

Proportion of participants needing additional hemodialysis sessions

Variations in serum-electrolyte levelsDuring the hemodialysis session preceding and the one following the intake of bowel preparation

Mean variation in serum-electrolyte levels between the hemodialysis session preceding and following the intake of bowel preparation

Diastolic blood pressureDuring the hemodialysis session preceding and the one following the intake of bowel preparation

Mean variation in diastolic blood pressure between the hemodialysis session preceding and following the intake of bowel preparation

Blood flow on dialysisDuring the hemodialysis session preceding and the one following the intake of bowel preparation

Mean variation in blood flow on dialysis between the hemodialysis session preceding and following the intake of bowel preparation

Adenoma detection rateDuring colonoscopy

Proportion of patients with at least one adenoma

Cecal intubation rateDuring colonoscopy

Proportion of endoscopic examinations reaching the cecum

Willingness to repeat the preparationDuring colonoscopy

Proportion of participants willing to use the same bowel preparation for future examinations

All-cause hospitalizationWithin a 30-day period

Proportion of participants hospitalized after bowel preparation intake for any cause

Interdialytic body weight gainDuring the hemodialysis session preceding and the one following the intake of bowel preparation

Mean increase in body weight from the hemodialysis session preceding the intake of bowel preparation to the one following the colonoscopy

Participants' tolerabilityDuring colonoscopy

Proportion of participants presenting nausea, bloating, vomiting, abdominal pain, and/or anal irritation

Cardiovascular eventsWithin a 30-day period

Proportion of participants with cardiovascular events (i.e. nonfatal myocardial infarction, acute coronary syndrome, and/or heart failure)

Participants' complianceDuring colonoscopy

Proportion of participants with intake of at least 75 percent of the bowel preparation

Adverse eventsDuring colonoscopy and the first hemodialysis session following colonoscopy

Proportion of participants with any adverse event occurred during the intake of bowel preparation

All-cause mortalityWithin a 30-day period

Proportion of participants who died after bowel preparation intake for any cause

Systolic blood pressureDuring the hemodialysis session preceding and the one following the intake of bowel preparation

Mean variation in systolic blood pressure between the hemodialysis session preceding and following the intake of bowel preparation

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