Chronic Kidney Diseases, Colon Cancer, Colon Polyp, Dialysis; Complications
Conditions
Keywords
Colonoscopy, Bowel cleansing, Adenoma detection, Polyethylene glycol, Hemodialysis
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.
Interventions
DRUG2-liters polyethylene glycol with citrate and simethicone
Low-volume polyethylene glycol-based bowel cleansing agent for colonoscopy.
DRUG4-liters polyethylene glycol with simethicone
High-volume polyethylene glycol-based bowel cleansing agent for colonoscopy.
DIETARY_SUPPLEMENTLow-residue diet
Diet before colonoscopy.
Sponsors
Alfasigma S.p.A.
Alfredo Di Leo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adequate bowel preparation | During colonoscopy | Proportion of participants with Boston Bowel Preparation Scale ≥6 with each segmental score ≥2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cecal intubation rate | During colonoscopy | Proportion of endoscopic examinations reaching the cecum |
| Participants' compliance | During colonoscopy | Proportion of participants with intake of at least 75 percent of the bowel preparation |
| Participants' tolerability | During colonoscopy | Proportion of participants presenting nausea, bloating, vomiting, abdominal pain, and/or anal irritation |
| Willingness to repeat the preparation | During colonoscopy | Proportion of participants willing to use the same bowel preparation for future examinations |
| Adverse events | During colonoscopy and the first hemodialysis session following colonoscopy | Proportion of participants with any adverse event occurred during the intake of bowel preparation |
| All-cause hospitalization | Within a 30-day period | Proportion of participants hospitalized after bowel preparation intake for any cause |
| All-cause mortality | Within a 30-day period | Proportion of participants who died after bowel preparation intake for any cause |
| Adenoma detection rate | During colonoscopy | Proportion of patients with at least one adenoma |
| Cardiovascular events | Within a 30-day period | Proportion of participants with cardiovascular events (i.e. nonfatal myocardial infarction, acute coronary syndrome, and/or heart failure) |
| Interdialytic body weight gain | During 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 |
| Variations in serum-electrolyte levels | During 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 |
| Systolic blood pressure | During 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 |
| Diastolic blood pressure | During 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 dialysis | During 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 |
| Emergency hemodialysis sessions | Within a 30-day period | Proportion of participants needing additional hemodialysis sessions |
Contacts
Primary ContactAlfredo Di Leo, MD PhD
Outcome results
None listed