Prucalopride in Postoperative Ileus

NCT02947269 | Completed Phase 3 DMC

• 1 other identifier: UOA-prucRCT1
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Ileus; Colorectal Surgery; Postoperative Complications

Outcome Measures

Primary Outcomes (1)

• Time until recovery of gastrointestinal function

  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 Outcomes (6)

• Time until passage of stool (in days)

  From date of surgery until discharge from hospital (14 days on average)

• Time until passage of flatus (in days)

  From date of surgery until discharge from hospital (14 days on average)

• Time until tolerance of solid oral diet (in days)

  From date of surgery until discharge from hospital (14 days on average)

• Presence of prolonged postoperative ileus

  From date of surgery until discharge from hospital (14 days on average)

• Levels of serum inflammatory markers (in pg/mL)

  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).

Other Outcomes (1)

• Rate of gastric emptying using the 13-carbon octanoate breath test

  This test will be undertaken on day 2 postoperatively, and will take approximately 4 hours

Study Arms (2)

Intervention group

EXPERIMENTAL

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

Placebo group

PLACEBO COMPARATOR

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

Interventions

Prucalopride DRUG

Prucalopride 2mg capsule

Also known as: Resolor, Resotrans

Intervention group

Placebo Oral Capsule DRUG

Placebo capsule

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Auckland, New Zealand: lead

Study Sites (1)

University of Auckland

Auckland, 1023, New Zealand

Location

Related Publications (1)

• Milne T, Liu C, O'Grady G, Woodfield J, Bissett I. Effect of prucalopride to improve time to gut function recovery following elective colorectal surgery: randomized clinical trial. Br J Surg. 2022 Jul 15;109(8):704-710. doi: 10.1093/bjs/znac121.

  PMID: 35639621 DERIVED

MeSH Terms

Conditions

Postoperative Complications

Interventions

prucalopride

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Ian Bissett

Study Record Dates

• First Submitted: October 23, 2016
• First Posted: October 27, 2016
• Study Start: October 25, 2017
• Primary Completion: August 30, 2020
• Study Completion: August 30, 2020
• Last Updated: September 29, 2021

Record last verified: 2021-09

Locations

NZ (1)