Prucalopride for Postoperative Ileus in Patients Undergoing Gastrointestinal Surgery

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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Ileus
• Intervention / Treatment: Drug: Prucalopride; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Department of Generay Surgery, Jinling hosptal, Medical School of Nanjing University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Consecutive patients undergoing elective gastric, small bowel, or partial colonic resection via laparotomy or laparoscopy.
2. Patients with American Society of Anaesthesiologists grading I-III
3. Informed consent available.

Exclusion Criteria:

1. Patients with stoma creation, extensive adhesiolysis, total or subtotal colectomy , or patients who had a history of total or subtotal colectomy.
2. Patients who developed intraoperative problems or complications, or had peritoneal carcinomatosis.
3. Patients who developed serious complications within 24 hours after surgery.
4. Those who received epidural anesthesia or analgesia.
5. Patients who received other prokinetic drugs.
6. Patients who were allergic to prucalopride.
7. Patients with severe comorbidity and/or organ(kidney, liver, and heart) dysfunction
8. Patients had complete bowel obstruction
9. Patients who have participated other clinical trials.
10. Patients who have short bowel(<200cm small bowel) or history of constipation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prucalopride; 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; 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; Other Names: Resolor
Placebo Comparator: Placebo; Vitamin C, 50mg, tablet	Drug: Placebo; Vitamin, 50mg, tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole blood white blood cell(WBC) count on postoperative day 1 and 3	whole blood white blood cell (WBC) count(*109/L)	postoperative day 1 and 3
Whole blood neutrophil percentage on postoperative day 1 and 3	neutrophil percentage(%)	postoperative day 1 and 3
Whole blood platelet level on postoperative day 1 and 3	platelet level(*109/L)	postoperative day 1 and 3
Serum C-reactive protein(CRP) level on postoperative day 1 and 3.	CRP level(mg/dL)	postoperative day 1 and 3
Serum interleukin-6(IL-6) level on postoperative day 1 and 3.	IL-6(pg/ml)	postoperative day 1 and 3
Serum procalcitonin(PCT) level on postoperative day 1 and 3.	PCT(ug/L)	postoperative day 1 and 3

Collaborators and Investigators

• Sponsor: Jinling Hospital, China
• Investigators: Principal Investigator: Jianfeng Gong, MD, Department of general surgery,Jinling hospital

Publications and helpful links

General Publications

• Gong J, Xie Z, Zhang T, Gu L, Yao W, Guo Z, Li Y, Lu N, Zhu W, Li N, Li J. Randomised clinical trial: prucalopride, a colonic pro-motility agent, reduces the duration of post-operative ileus after elective gastrointestinal surgery. Aliment Pharmacol Ther. 2016 Apr;43(7):778-89. doi: 10.1111/apt.13557. Epub 2016 Feb 15.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: November 26, 2013
• First Submitted That Met QC Criteria: December 6, 2013
• First Posted (Estimate): December 9, 2013

Study Record Updates

• Last Update Posted (Estimate): September 30, 2016
• Last Update Submitted That Met QC Criteria: September 29, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Gastrointestinal Diseases; Randomised trial; Prucalopride; 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; Laxatives; Serotonin 5-HT4 Receptor Agonists; Prucalopride
• Other Study ID Numbers: RIGS-2013-PRU