Effectiveness of Prokinetic Agents in Improving Abdominal Discomfort at Colonoscopy

A Randomized Controlled Double-blinded of Effectiveness of Prokinetic Agents in Improving Abdominal Discomfort at Pre- and Post- Colonoscopy

colonoscopy has been a preferred modality for colorectal screening which efficiently reduce in morbidity and mortality of the disaese. Although colonoscopy is a safe procedure, some patients may be suffered from major and minor complications. Abdominal discomfort (approximately 30%) usually persisted for 2 days after colonoscopy. These unsatisfactory experiences might affect the patients' willingness to return for a repeat colonoscopy, which the loss of adherence eventually reduce the effectiveness of colorectal cancer screening and surveillance.

Furthermore, during colonoscopy preparation, the patients are required to take large volume Polyethylene glycol-electrolyte lavage (PEG-EL) solution for bowel preparation which possibly lead to unpleasant gastrointestinal symptoms likewise.

Prokinetic agents are a class of drugs that promoted gastrointestinal motility and, thereby, decrease transit time. This stimulatory effect was considered clinically relevant to the management of disorders characterized by impaired motility, such as gastro-esophageal reflux, gastroparesis, intestinal pseudo-obstruction, and colonic inertia. Prokinetic agents have various mechanism such as Cholinergic agonists, Dopamine antagonists (i.e.Domperidone, Metoclopramide), Serotonergic agonists (i.e. Cisapride, Prucalopride,Mosapride). Interestingly, these drugs have been used to minimize the unpleasant abdominal symptoms from colonoscopy.

The objective of this study is to examine the efficacy of a prokinetic agent in alleviating abdominal discomfort during the period of colonoscopy preparation and aftercolonoscopy consecutively.

Study Overview

• Status: Enrolling by invitation
• Conditions: Abdominal Pain
• Intervention / Treatment: Drug: Itopride; Other: Placebo; Drug: Domperidone

Detailed Description

The participants will be randomly selected into one of the three arms of this report's diagram (1:1:1 ratio) drawing of a sealed, opaque envelope by one of the surgical residents in charge or by the attending surgeon. The participants in each group will receive an envelope containing pills of identical appearance, each of Domperidone 10 mg, Itopride 50 mg or placebo. Both the attending physicians and the participants are blinded to the kind of study medication contained in the envelope.

From the regular protocol for colonoscopy preparation, no solid foods are allowed except low residue diet during three days before the procedure. On the next day, only liquid diet consumption is allowed. On the day prior to colonoscopy, the patients can have only clear liquid and ad libitum throughout the day until midnight. Additionally, the patients are instructed to take one pill at 8.00 AM, 12.00 AM, 4.30 PM respectively. They are also informed to begin consuming the 3 liters of PEG-EL at 5.00 PM and complete it within 3 hours. Lastly, they are instructed to take the fourth pill at 6.00 AM on the day of colonoscopy. At the colonoscopy unit, the patients will be interviewed regarding the severity of abdominal discomfort during the preparation period after consuming the 3 liters of PEG-EL using a 4-point scale (1=absent, 2=mild, 3=moderate, 4=severe). After finish the procedure, patients are informed to continue the study medication for three days consecutively.

The interviewer will make a phone call to the individuals at the first and third day after the procedure to confirm compliance of the study medication and inquiry about the severity of abdominal discomfort after procedure by using the same 4-point scale. If the patient can't be reached by a phone call or fail to continue the medication, this patient is classified as a drop out.

All data is collected by the main investigator from the patient chart and data recording form. Statistical analysis is performed using SPSS version 18. Patient characteristic and numerical data are reported by descriptive statistic such as mean, standard deviation. Parametric data is compared between groups using Chi-square, logistic regression analysis.Statistical significance is set at a level of p<0.05.

• Study Type: Interventional
• Enrollment (Anticipated): 525
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Bankok
    • Bangkok, Bankok, Thailand, 10400
      • Chairat Supsamutchai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who are an outpatient scheduled for elective colonoscopy at Ramathibodi hospital
• Age between 18 to 80 years old
• American Society of Anesthesiologists (ASA) classification 1-2

Exclusion Criteria:

• Patients who reject to participate or withdrawal from the research
• History of Domperidone or Itopride allergy
• Patients who do not complete taking the study medication
• Patients who have ostomy or history of subtotal colectomy
• Patients who are diagnosed active colitis i.e. ulcerative colitis, TB colitis
• Take any pain reliever agent during the study period
• Patients who are unable to communicate comprehensibly
• Severe renal or hepatic impairment
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Colonoscopy preparation by PEG-EL with Itopride; Regular protocol for colonoscopy preparation, no solid foods are allowed except low residue diet during three days before the procedure. On the next day, only liquid diet consumption is allowed.On the day prior to colonoscopy, the patients can have only clear liquid and ad libitum throughout the day until midnight. They are also informed to begin consuming the 3 liters of PEG-EL at 5.00 PM and complete it within 3 hours one day befor colonoscopy.	Drug: Itopride; the patients are instructed to take one pill of Itopride at 8.00 AM, 12.00 AM, 4.30 PM respectively before the dat of colonoscopy. Lastly, they are instructed to take the fourth pill at 6.00 AM on the day of colonoscopy.; Other Names: Colonoscopy preparation by PEG-EL with Itopride
Placebo Comparator: Colonoscopy preparation by PEG-EL with Placebo; Regular protocol for colonoscopy preparation, no solid foods are allowed except low residue diet during three days before the procedure. On the next day, only liquid diet consumption is allowed.On the day prior to colonoscopy, the patients can have only clear liquid and ad libitum throughout the day until midnight. They are also informed to begin consuming the 3 liters of PEG-EL at 5.00 PM and complete it within 3 hours one day befor colonoscopy.	Other: Placebo; the patients are instructed to take one pill of placebo at 8.00 AM, 12.00 AM, 4.30 PM respectively before the dat of colonoscopy. Lastly, they are instructed to take the fourth pill at 6.00 AM on the day of colonoscopy.; Other Names: Colonoscopy preparation by PEG-EL with Placebo
Active Comparator: Colonoscopy preparation by PEG-EL with Domperidone; Regular protocol for colonoscopy preparation, no solid foods are allowed except low residue diet during three days before the procedure. On the next day, only liquid diet consumption is allowed.On the day prior to colonoscopy, the patients can have only clear liquid and ad libitum throughout the day until midnight. They are also informed to begin consuming the 3 liters of PEG-EL at 5.00 PM and complete it within 3 hours one day befor colonoscopy.	Drug: Domperidone; the patients are instructed to take one pill of Domperidone at 8.00 AM, 12.00 AM, 4.30 PM respectively before the dat of colonoscopy. Lastly, they are instructed to take the fourth pill at 6.00 AM on the day of colonoscopy.; Other Names: Colonoscopy preparation by PEG-EL with Domperidone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
abdominal pain	the severity of abdominal pain using a 4-point scale (1=absent, 2=mild, 3=moderate, 4=severe)	24 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
abdominal pain	the severity of abdominal pain using a 4-point scale (1=absent, 2=mild, 3=moderate, 4=severe)	48 hour
abdominal pain	the severity of abdominal pain using a 4-point scale (1=absent, 2=mild, 3=moderate, 4=severe)	72 hour

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Study Chair: Chairat Supsamutchai, MD, Ramathibodi Hospital

Publications and helpful links

General Publications

• de Jonge V, Sint Nicolaas J, van Baalen O, Brouwer JT, Stolk MF, Tang TJ, van Tilburg AJ, van Leerdam ME, Kuipers EJ; SCoPE consortium. The incidence of 30-day adverse events after colonoscopy among outpatients in the Netherlands. Am J Gastroenterol. 2012 Jun;107(6):878-84. doi: 10.1038/ajg.2012.40. Epub 2012 Mar 6.
• Quigley EMM. Prokinetics in the Management of Functional Gastrointestinal Disorders. Curr Gastroenterol Rep. 2017 Sep 8;19(10):53. doi: 10.1007/s11894-017-0593-6.
• Panteris V, Haringsma J, Kuipers EJ. Colonoscopy perforation rate, mechanisms and outcome: from diagnostic to therapeutic colonoscopy. Endoscopy. 2009 Nov;41(11):941-51. doi: 10.1055/s-0029-1215179. Epub 2009 Oct 28.
• Pignone M, Saha S, Hoerger T, Mandelblatt J. Cost-effectiveness analyses of colorectal cancer screening: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2002 Jul 16;137(2):96-104. doi: 10.7326/0003-4819-137-2-200207160-00007.
• Mishima Y, Amano Y, Okita K, Takahashi Y, Moriyama N, Ishimura N, Furuta K, Ishihara S, Adachi K, Kinoshita Y. Efficacy of prokinetic agents in improving bowel preparation for colonoscopy. Digestion. 2008;77(3-4):166-72. doi: 10.1159/000141040. Epub 2008 Jun 25.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2019
• Primary Completion (Anticipated): October 30, 2022
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): September 2, 2021
• Last Update Submitted That Met QC Criteria: September 1, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Abdominal Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dopamine Agents; Dopamine Antagonists; Domperidone
• Other Study ID Numbers: 2019/524

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No