Effect of Mosapride on Postoperative Ileus in Patients Undergoing Colorectal Surgery (ILEUS)

Postoperative Ileus is defined as the transient postoperative functional inhibition of propulsive bowel activity. The ethiology of this process can best be described as multifactorial. In its pathogenesis different mechanisms are involved such as hormones and neuropeptides, inflammation, narcotics and the Autonomic nervous system. Is one of the most common causes of prolonged hospital stays after abdominal surgery, thereby increasing health-care resource utilization. More importantly, it causes patient discomfort in the form of nausea, vomiting, and stomach cramps. It has a variable duration but is usually solved in 3 to 4 days. Prolonged Ileus is associated with postoperative complications like an increase on urinary and pulmonary infections, profound venous thrombosis and wound-site complications.

Mosapride is a prokinetic agent that acts as a selective serotonin agonist (5- HT4) that facilitates acetylcholine release from the intrinsic plexus. This accelerates gastric emptying and propulsive peristaltic movements on the lower intestines. Mosapride has no action over the central nervous system therefore the lesser side effects like cardiac arrhythmias and extrapyramidal symptoms. For being a safer drug we chose it to be the center of our research.

Two randomized controlled trials studied Mosapride concluding it shortens PI after colorectal surgery. However these trials took place on specific populations (Orientals) with less than 50 patients and only one of them included laparoscopic treatment specifically. Also the end point of these studies didn't consider the impact of PI over hospital stay or costs to the health system.

We therefore decided to conduct a prospective randomized study in patients undergoing laparoscopic colorectal surgery for colon cancer. The patients will be randomized to receive treatment or placebo after surgery. With this study we intend to prove that patients treated with mosapride immediately after surgery suffer from shorter postoperative ileus with earlier oral intake and shorter hospital stay.

The primary aim of the trial is to assess the effectiveness of the use of Mosapride in shortening the duration of the Postoperative ileus in patients undergoing colorectal laparoscopic surgery. The trial hypothesis is that the standardized use of Mosapride immediately after colorectal laparoscopic surgery is safe and accelerates the recovery of propulsive bowel activity, thereby shortening postoperative ileus and hospital stay.

Study Overview

• Status: Unknown
• Conditions: Postoperative Ileus
• Intervention / Treatment: Drug: Placebo; Drug: Mosapride

Detailed Description

Methods. Design. Design A randomized controlled trial, triple blind with placebo. Study population Patients undergoing laparoscopic colorectal surgery. Italian Hospital of Buenos Aires. Argentina.

Inclusion and exclusion criteria

Participants will be eligible provided they are at least 18 years of age and under 85, are about to undergo colonic or upper rectum surgery with the diagnose of cancer o malignant polyp. People will be excluded if:

• They refuse to participate from the trial or the process of informed consent
• Have known allergies or hypersensitivity to Mosapride or lactose (used for placebo)
• Patients with ascites, hepatic metastases or carcinomatosis
• Patients who cannot receive Non-steroidal anti-inflammatory drugs
• Pregnancy or women at a fertile age who do not use double contraceptive agents
• Patients with conversion to laparotomy
• Patients with a Rectal tumor beneath 11 cm requiring low or ultralow rectal resection
• Patients with an stoma or who underwent simultaneous resection of other organs

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Virginia M Cano Busnelli, MD; Phone Number: 54 11 66128852; Email: virginia.cano@hospitalitaliano.org.ar
• Study Contact Backup: Name: Natalia L Gomez, MD; Phone Number: 54 11 68364732; Email: natalia.gomez@hospitalitaliano.org.ar

Study Locations

• Argentina
  • State Capital
    • Buenos Aires, State Capital, Argentina, 1199
      • Recruiting
      • Italian Hospital of Buenos Aires
      • Principal Investigator: Virginia M Cano Busnelli, MD
      • Sub-Investigator: Natalia L Gomez, MD
      • Sub-Investigator: Jeremias Goransky Patiño, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 85 years old
• Underwent colonic or upper rectum laparoscopic surgery with diagnose of cancer or malignant polyp
• Were operated on Italian Hospital of Buenos Aires

Exclusion Criteria:

• They refuse to participate from the trial or the process of informed consent
• Have known allergies or hypersensitivity to Mosapride or lactose (used for placebo)
• Patients with ascites, hepatic metastases or carcinomatosis
• Patients who cannot receive Non-steroidal anti-inflammatory drugs
• Pregnancy or women at a fertile age who do not use double contraceptive agents
• Patients with conversion to laparotomy
• Patients with a Rectal tumor beneath 11 cm requiring low or ultralow rectal resection
• Patients with an derivative stoma or who underwent simultaneous resection of other organs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo arm: intake of placebo (Lactose). 1 pill of the same characteristics as Mosapride every 8 hs with 30 ml tap water. This will begin on postoperative day 1 until discharge from Hospital or unacceptable toxicity develops.	Drug: Placebo; 1 pill of the same characteristics as Mosapride every 8 hs with 30 ml tap water. This will begin on postoperative day 1 until discharge from Hospital or unacceptable toxicity develops.; Other Names: Lactose
Active Comparator: Mosapride; Mosapride arm: intake of active drug (Mosapride). 15 mg per day divided into 3 oral intakes of 5 mg each (1 pill of Mosapride every 8 hs with 30 ml tap water). This treatment will begin on postoperative day 1 until discharge from Hospital or unacceptable toxicity develops.	Drug: Mosapride; 15 mg per day divided into 3 oral intakes of 5 mg each (1 pill of Mosapride every 8 hs with 30 ml tap water). This treatment will begin on postoperative day 1 until discharge from Hospital or unacceptable toxicity develops.; Other Names: Mosar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days after Surgery until the recovery of bowel movement	Effect of the administration of mosapride on the immediate postoperative on the recovery of bowel movements.	1 to 5 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients to develop adverse reactions to Mosapride	To evaluate the safety of the administration of Mosapride after colorectal laparoscopic surgery.	1 to 5 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days of Hospital stay after surgery.	To assess the effect of Mosapride on the reduction of Hospital stay days	18 months (end of protocol)

Collaborators and Investigators

• Sponsor: Hospital Italiano de Buenos Aires
• Investigators: Study Director: Carlos A Vaccaro, MD, Hospital Italiano de Buenos Aires

Publications and helpful links

General Publications

• Toyomasu Y, Mochiki E, Morita H, Ogawa A, Yanai M, Ohno T, Fujii T, Tsutsumi S, Asao T, Kuwano H. Mosapride citrate improves postoperative ileus of patients with colectomy. J Gastrointest Surg. 2011 Aug;15(8):1361-7. doi: 10.1007/s11605-011-1567-x. Epub 2011 May 24.
• Narita K, Tsunoda A, Takenaka K, Watanabe M, Nakao K, Kusano M. Effect of mosapride on recovery of intestinal motility after hand-assisted laparoscopic colectomy for carcinoma. Dis Colon Rectum. 2008 Nov;51(11):1692-5. doi: 10.1007/s10350-008-9407-0. Epub 2008 Jun 27.
• Seta ML, Kale-Pradhan PB. Efficacy of metoclopramide in postoperative ileus after exploratory laparotomy. Pharmacotherapy. 2001 Oct;21(10):1181-6. doi: 10.1592/phco.21.15.1181.33888.
• Davidson ED, Hersh T, Brinner RA, Barnett SM, Boyle LP. The effects of metoclopramide on postoperative ileus. A randomized double-blind study. Ann Surg. 1979 Jul;190(1):27-30. doi: 10.1097/00000658-197907000-00006.
• Furness JB, Costa M. Adynamic ileus, its pathogenesis and treatment. Med Biol. 1974 Apr;52(2):82-9. No abstract available.
• Jepsen S, Klaerke A, Nielsen PH, Simonsen O. Negative effect of Metoclopramide in postoperative adynamic ileus. A prospective, randomized, double blind study. Br J Surg. 1986 Apr;73(4):290-1. doi: 10.1002/bjs.1800730414.
• Tollesson PO, Cassuto J, Rimback G, Faxen A, Bergman L, Mattsson E. Treatment of postoperative paralytic ileus with cisapride. Scand J Gastroenterol. 1991 May;26(5):477-82. doi: 10.3109/00365529108998569.
• Brown TA, McDonald J, Williard W. A prospective, randomized, double-blinded, placebo-controlled trial of cisapride after colorectal surgery. Am J Surg. 1999 May;177(5):399-401. doi: 10.1016/s0002-9610(99)00071-9.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: January 31, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimate): February 6, 2014

Study Record Updates

• Last Update Posted (Estimate): December 17, 2015
• Last Update Submitted That Met QC Criteria: December 16, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Mosapride; Postoperative Ileus; Colorectal laparoscopic surgery; Prolonged postoperative ileus
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Obstruction; Ileus; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Serotonin Agents; Serotonin Receptor Agonists; Mosapride
• Other Study ID Numbers: 2104