Prucalopride in Postoperative Ileus

September 27, 2021 updated by: A/Prof Ian Bissett, University of Auckland, New Zealand

A Randomized Double-blind Placebo Controlled Trial of Prucalopride to Reduce the Duration of Postoperative Ileus in Patients Undergoing Elective Colorectal Surgery

Postoperative ileus (POI) refers to the period of gut dysmotility that occurs after abdominal surgery. Patients with POI are unable to eat, suffer ongoing nausea and vomiting, are unable to open their bowels and have a prolonged hospital stay. Research at ADHB shows that 25% of patients will have a prolonged POI after elective bowel resection, which makes it the most common major complication after colorectal surgery. Clinicians currently lack a definitive medication to prevent or treat POI, which means POI causes patients ongoing morbidity and places a significant drain on healthcare resources. Serotonin plays an important role in gut motility. Evidence suggests that serotonin agonists, such as prucalopride, increase gut transit and may have anti-inflammatory properties. The hypothesis of this study is that Prucalopride given pre-operatively and continued post-operatively in patients having an elective bowel resection will improve gut function recovery after surgery and reduce POI.

The investigators' proposed study is a double-blinded randomised controlled trial of prucalopride compared to an identical placebo tablet, in patients having an elective bowel resection at Auckland City Hospital. Patients will receive a single tablet of Prucalopride or placebo 2-3 hours preoperatively and then daily after operation for a maximum of 6 days. The primary endpoint will be return to bowel function defined by the time to tolerate a solid diet and pass stool. In addition, the investigators plan to assess postoperative gastric emptying rates using the safe and non-invasive carbon breath test method. This will allow the investigators to determine the effects of prucalopride on the stomach, and support its role as a gastric prokinetic.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • New Zealand
      • Auckland, New Zealand, 1023
        • University of Auckland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patients from Auckland District Health Board catchment
  • Age 18 or older
  • Elective and subacute surgery
  • Right hemicolectomy, left hemicolectomy, sigmoid colectomy, anterior resection, Hartmann's procedure, subtotal colectomy
  • Operation with or without the formation of a colostomy
  • Indication for operation: colon cancer, diverticular disease, gynaecological
  • Able to understand risks and benefits of the study
  • Able to give informed consent

Exclusion Criteria:

  • ASA 4 or greater
  • Allergy to any serotonin medication
  • Active inflammatory bowel disease
  • Planned formation of an ileostomy during surgery
  • Moderate to severe renal impairment (Creatinine clearance<50mL/min/1.73m2)
  • Severe hepatic impairment (Child-Pugh C)
  • Pregnancy
  • Pre-existing gut dysmotility disorder including endocrine, metabolic or neurological cause
  • Pre-operative malnutrition requiring parenteral nutrition
  • Inability to give consent or participate in post-operative assessments due to dementia, cognitive impairment, language difficulties, delirium

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Intervention group
Patients will receive an oral capsule containing 2mg Prucalopride 2-3 hours preoperatively. Study medication (2mg oral Prucalopride daily) will continue for 6 days postoperatively or until the patient has achieved the study's primary outcome.
Drug: Prucalopride
Prucalopride 2mg capsule
Other Names:
  • Resolor
  • Resotrans
PLACEBO_COMPARATOR: Placebo group
Patients will receive an oral capsule containing a placebo 2-3 hours preoperatively. Study medication (placebo) will continue for 6 days preoperatively or until the patient has achieved the study's primary outcome.
Drug: Placebo Oral Capsule
Placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time until recovery of gastrointestinal function
Time Frame: From date of surgery until discharge from hospital (14 days on average)
Recovery of GI function is defined by the later time point (in days) of time to passage of stool AND time to tolerance of a solid or semi-solid diet. Patients will be reviewed twice per day using a structured questionnaire.
From date of surgery until discharge from hospital (14 days on average)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time until passage of stool (in days)
Time Frame: From date of surgery until discharge from hospital (14 days on average)
From date of surgery until discharge from hospital (14 days on average)
Time until passage of flatus (in days)
Time Frame: From date of surgery until discharge from hospital (14 days on average)
From date of surgery until discharge from hospital (14 days on average)
Time until tolerance of solid oral diet (in days)
Time Frame: From date of surgery until discharge from hospital (14 days on average)
From date of surgery until discharge from hospital (14 days on average)
Presence of prolonged postoperative ileus
Time Frame: From date of surgery until discharge from hospital (14 days on average)
Prolonged postoperative ileus is defined as presence of 2 or more of the following criteria on or after day 4 postoperatively: nausea or vomiting, inability to tolerate a solid or semi-solid oral diet, abdominal distension, absence of flatus and stool, radiological evidence of ileus.
From date of surgery until discharge from hospital (14 days on average)
Levels of serum inflammatory markers (in pg/mL)
Time Frame: Inflammatory markers will be collected preoperatively, day 1 and 3 postoperatively. Blood samples will be stored after collection for later testing (up to 1 year).
Markers to be tested: CRP, IL1beta, IL6, IL8, IL12, TNFalpha
Inflammatory markers will be collected preoperatively, day 1 and 3 postoperatively. Blood samples will be stored after collection for later testing (up to 1 year).
Length of postoperative stay (in days)
Time Frame: From date of surgery until discharge from hospital (14 days on average)
From date of surgery until discharge from hospital (14 days on average)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of gastric emptying using the 13-carbon octanoate breath test
Time Frame: This test will be undertaken on day 2 postoperatively, and will take approximately 4 hours
A subgroup of 40 patients will be investigated for this study
This test will be undertaken on day 2 postoperatively, and will take approximately 4 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Auckland, New Zealand

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 25, 2017

Primary Completion (ACTUAL)

August 30, 2020

Study Completion (ACTUAL)

August 30, 2020

Study Registration Dates

First Submitted

October 23, 2016

First Submitted That Met QC Criteria

October 25, 2016

First Posted (ESTIMATE)

October 27, 2016

Study Record Updates

Last Update Posted (ACTUAL)

September 29, 2021

Last Update Submitted That Met QC Criteria

September 27, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UOA-prucRCT1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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