Clinical trial NCT02178033: The Impact of Split Dose of Low-volume Polyethylene Glycol on Adenoma Detection Rate
Official title: The Impact of Split Dose of Low-volume Polyethylene Glycol on Adenoma Detection Rate: a Randomized, Investigator Blind, Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Colonic Adenomas
Keywords: adenoma detection rate, screening colonoscopy
Lead sponsor: Valduce Hospital
Sponsor class: OTHER
Collaborators: name: Istituto Clinico Humanitas
name: Istituti Ospitalieri di Cremona
name: Nuovo Regina Margherita Hospital
First posted: 2014-06-30
Enrollment: 514
Sex: ALL
Minimum age (years): 50
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: An adequate level of bowel preparation is crucial for the efficacy and safety of colonoscopy. Strong evidences suggest that bowel-preparation quality shows an inverse correlation with length of the interval between the end of cleansing agent intake and the start of colonoscopy (shorter intervals are associated with better preparation levels). Accordingly, the use of a split-dose administration regimen has been demonstrated to significantly improve the quality of preparation, besides patient acceptability, as compared with standard administration the day before colonoscopy. All randomized controlled trials comparing split versus standard preparations were primarily aimed at assessing the quality of colon cleansing, by means of either validated or not-validated colon cleansing scales. The impact of a split dose regimen on objective colonoscopy performance measures such as adenoma detection rate (ADR) has never been specifically and prospectively evaluated.

The present study is aimed at evaluating whether the split-dose preparation regimen is associated with an increase of adenoma detection.

For this purpose, asymptomatic subjects aged 50-69, undergoing screening colonoscopy for positive immunologic fecal occult blood test are randomized in a 1:1 ratio to receive low-volume (2L) PEG plus ascorbic acid solution either in a split-dose (study arm) or in a full-dose regimen (control arm).

Treatments are allocated using a computer-generated, randomized code list. The treatment allocation is concealed and is accomplished at the screening visit through non-research personnel who is not involved in the study. To ensure masking, the endoscopists who perform the colonoscopies are not involved in the randomization process and in the pre-procedure data collection.

In this study the the primary outcome measure was the proportion of patients with at least one adenoma (Adenoma Detection Rate) in each harm. Data on bowel cleansing, patient compliance, tolerability and acceptability were also collected.

A sample size of at least 514 patients (257 in each arm) was calculated, by hypothesizing a relative increase of 25% in the adenoma detection rate in the split dose preparation group, assuming a 40% prevalence of one or more adenoma in FIT-positive patients undergoing screening colonoscopy (significance level 0.05, 90% power).

Detailed description: All participants will receive the same low-volume (2L) PEG plus ascorbic acid solution (MOVIPREP®\*, Norgine, Harefield, United Kingdom; each liter containing 100.0 g macrogol 3350, 7.5 g sodium sulfate,2.7 g sodium chloride, 1.0 g potassium chloride, 4.7 g ascorbic acid, 5.9 g sodium ascorbate, and lemon or orange flavoring).

Patients allocated in the "control arm" will receive the whole preparation the day before colonoscopy, whereas, patient randomly allocated to the "active treatment" will take one liter of the bowel preparation the evening before the procedure and the remaining liter the day of the procedure.

Participants will also receive a standardized low-fiber diet before the colonoscopy, avoiding fruit, legumes or vegetables for 3 days before the procedure. They will have a normal breakfast and a light lunch on the day before the procedure, but no solid food will be permitted since then. Liquid food (e.g., clear soup or yoghurt) will be permitted for the evening meal. Clear fluids can be taken at any time, until 2 hours before the procedure.

Treatments are allocated using a computer-generated, randomized code list. The treatment allocation is concealed and is accomplished at the screening visit through non-research personnel who is not involved in the study. To ensure masking, the endoscopists who perform the colonoscopies are not involved in the randomization process and in the pre-procedure data collection.

Data on patient compliance, tolerability and acceptability are collected on the morning of colonoscopy, immediately before the procedure, by a nurse questioned through a standardised questionnaire. The endoscopist is not allowed to take part in the questioning or to supervise the questionnaire.

Eligibility criteria: Inclusion Criteria:

* asymptomatic subjects aged 50-69 participating to regional screening program and undergoing outpatient colonoscopy for positive immunologic fecal occult blood test.

Exclusion criteria:

* patients undergoing colonoscopy as primary screening test
* patients undergoing colonoscopy for symptoms or post-polypectomy/ cancer surveillance
* patients with history of negative large bowel endoscopy within the previous 5 years
* patients with personal history of hereditary syndromes
* patients with history of colonic resection and inflammatory bowel disease
* patients with a history of radiation therapy to abdomen or pelvis
* patients with a history of severe cardiovascular, pulmonary, liver or renal disease
* patients with unstable psychiatric illness
* patients at risk for inhalation
* patients on ant-platelet therapy or anticoagulation at the time of endoscopy procedure, preventing polyp resection
* patient with known hypersensitivity or contraindications (i.e., patients with phenylketonuria or glucose-6-phosphate dehydrogenase deficiency) to the study product
* patients who are not able or refuse to provide informed written consent

Primary outcomes:
measure: Adenoma Detection Rate
timeFrame: 1 year
Secondary outcomes:
measure: Advanced Adenoma Detection Rate
timeFrame: 1 year
measure: Flat/depressed Adenoma Detection Rate
timeFrame: 1 year
measure: Proximal sessile serrated lesion detection rate
timeFrame: 1 year
measure: Number of adenomas per patient
timeFrame: 1 year
measure: Number of advanced adenomas per patient
timeFrame: 1 year
measure: Number of proximal adenomas
timeFrame: 1 year
measure: Quality of bowel preparation
timeFrame: 1 year
Other outcomes:
Locations:
city: Como
country: Italy
facility: Ospedale VAlduce, Gastroenterology Unit
city: Milano
country: Italy
facility: IRCCS Istituto Clinico Humanitas; Gastroenterology Unit
Study officials:
affiliation: Ospedale Valduce, Gastroenterology Unit, Via Dante 10, 22100, Como, Italy.
name: Franco Radaelli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Radaelli F, Paggi S, Hassan C, Senore C, Fasoli R, Anderloni A, Buffoli F, Savarese MF, Spinzi G, Rex DK, Repici A. Split-dose preparation for colonoscopy increases adenoma detection rate: a randomised controlled trial in an organised screening programme. Gut. 2017 Feb;66(2):270-277. doi: 10.1136/gutjnl-2015-310685. Epub 2015 Dec 9.