Clinical trial NCT04709770: Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Kidney Diseases
Colon Polyp
Dialysis; Complications
Colon Cancer
Keywords: Colonoscopy
Bowel cleansing
Adenoma detection
Polyethylene glycol
Hemodialysis
Lead sponsor: University of Bari
Sponsor class: OTHER
Collaborators: name: Alfasigma S.p.A.
First posted: 2021-01-14
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adequate bowel preparation
timeFrame: During colonoscopy
Secondary outcomes:
measure: Adenoma detection rate
timeFrame: During colonoscopy
measure: Cecal intubation rate
timeFrame: During colonoscopy
measure: Participants' compliance
timeFrame: During colonoscopy
measure: Participants' tolerability
timeFrame: During colonoscopy
measure: Willingness to repeat the preparation
timeFrame: During colonoscopy
measure: Adverse events
timeFrame: During colonoscopy and the first hemodialysis session following colonoscopy
measure: All-cause hospitalization
timeFrame: Within a 30-day period
measure: All-cause mortality
timeFrame: Within a 30-day period
measure: Emergency hemodialysis sessions
timeFrame: Within a 30-day period
measure: Cardiovascular events
timeFrame: Within a 30-day period
measure: Interdialytic body weight gain
timeFrame: During the hemodialysis session preceding and the one following the intake of bowel preparation
measure: Variations in serum-electrolyte levels
timeFrame: During the hemodialysis session preceding and the one following the intake of bowel preparation
measure: Systolic blood pressure
timeFrame: During the hemodialysis session preceding and the one following the intake of bowel preparation
measure: Diastolic blood pressure
timeFrame: During the hemodialysis session preceding and the one following the intake of bowel preparation
measure: Blood flow on dialysis
timeFrame: During the hemodialysis session preceding and the one following the intake of bowel preparation
Other outcomes:
Locations:
Study officials:
affiliation: University of Bari
name: Alfredo Di Leo, MD PhD
role: PRINCIPAL_INVESTIGATOR
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