Prucalopride for Postoperative Ileus in Patients Undergoing Gastrointestinal Surgery

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect and safety of prucalopride on recovery of gastrointestinal function in patient undergoing major gastrointestinal surgery. The investigators hypothesize that patients who take prucalopride after major gastrointestinal surgery will have shorter duration of postoperative ileus.

Detailed Description
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Postoperative ileus (POI), an interruption of bowel motility function, virtually occurs in all patients undergoing major gastrointestinal(GI) surgery. This functional impairment persists for a variable duration, usually resolving within 1 day in the small intestine, 1 to 3 days in the stomach and 3 to 5 days in the colon. Therefore, time of return of colonic function is the the major determinant of duration of POI. Attempts to reduce the duration of POI have prompted the implementation of fast track surgery including early removal of the nasogastric tube, early feeding, alvimopan, gum chewing, and prompt ambulation. However, it is still reported to be more than 4-5 days in most of the randomized trial. Therefore, methods specifically aiming at promoting postoperative colon motility may further enhance the GI function recovery, and prucalopride may be one of the options. Prucalopride, a substituted benzamide with selective 5-HT4 agonist activity, has been shown previously to significant improve colon motility and transit, but it only has mild effect on gastric or small bowel transit. The drug is well tolerated with no significant adverse effects. Recently, prucalopride has been approved in Europe and America for the symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief. However, its usage in the postoperative period has not been tested. This study will test the ability and safety of prucalopride given 24hrs after GI surgery to hasten the recovery of GI function.

Official Title
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A Randomized, Controlled, Double-blind Efficacy and Tolerability Study Of Prucalopride For The Treatment Of Postoperative Ileus In Patients Undergoing Gastrointestinal Surgery

Conditions
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Postoperative Ileus

Intervention / Treatment
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* Drug: Prucalopride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive patients undergoing elective gastric, small bowel, or partial colonic resection via laparotomy or laparoscopy. Patients with American Society of Anaesthesiologists grading I-III Informed consent available. Exclusion Criteria: Patients with stoma creation, extensive adhesiolysis, total or subtotal colectomy , or patients who had a history of total or subtotal colectomy. Patients who developed intraoperative problems or complications, or had peritoneal carcinomatosis. Patients who developed serious complications within 24 hours after surgery. Those who received epidural anesthesia or analgesia. Patients who received other prokinetic drugs. Patients who were allergic to prucalopride. Patients with severe comorbidity and/or organ(kidney, liver, and heart) dysfunction Patients had complete bowel obstruction Patients who have participated other clinical trials. Patients who have short bowel(<200cm small bowel) or history of constipation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prucalopride<br>Prucalopride, 2mg, tablet. First given 24 hours after surgery beginning on POD 1,until bowel movements or for a maximum of 7 days of postoperative treatment | Drug: Prucalopride<br>* Prucalopride, 2mg, tablet. First given 24 hours after surgery beginning on POD 1,until bowel movements or for a maximum of 7 days of postoperative treatment<br>* Other names: Resolor;|
| Placebo Comparator: Placebo<br>Vitamin C, 50mg, tablet | Drug: Placebo<br>* Vitamin, 50mg, tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to defaecation, measured in hours, from the time the surgery ends till the first observed passage of stool |  | up to 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of first passing flatus reported by the patients(hours) |  | up to 30 days after surgery | 
| Time to resume solid diet or total enteral nutrition(TEN)(days) |  | up to 30 days after surgery | 
| Length of postoperative hospital stay (LOS)(days) |  | participants will be followed for the duration of postoperative hospital stay, an expected average of 8 days | 
| Overall post-operative complication rate defined according to the Clavien-Dindo Classification |  | up to 30 days after surgery | 
| Overall cost (RMB) |  | participants will be followed for the duration of postoperative hospital stay, an expected average of 8 days | 
| Pain scores on visual analogue scale (from 0 which implies no pain at all, to 10 which implies the worst pain imaginable) on the first 3 postoperative days and postoperative analgesic requirement (number of doses on 50-mg Pethidine) |  | up to postoperative day 3 | 
| Time to walk independently(days) |  | up to 30 days after surgery | 
| Hospital Readmission Rates Post 30-day Discharge |  | up to 30 days after discharge | 
| Length of postoperative ICU stay (days) |  | up to 30 days after surgery | 
| Incidence of adverse events related to drug usage | Diarrhoea,Flatulence,Nausea,Abdominal pain,Headaches,Menstrual disorder,Dizziness ,Skeletal pain,ECG nodal arrhythmia | up to 7 days after drug usage | 
| Reinsertion of nasogastric tube |  | up to 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prucalopride, Gastrointestinal Diseases, Postoperative ileus, Randomised trial