Clinical trial NCT02947269: Prucalopride in Postoperative Ileus
Official title: A Randomized Double-blind Placebo Controlled Trial of Prucalopride to Reduce the Duration of Postoperative Ileus in Patients Undergoing Elective Colorectal Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Ileus
Colorectal Surgery
Postoperative Complications
Lead sponsor: University of Auckland, New Zealand
Sponsor class: OTHER
First posted: 2016-10-27
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Time until recovery of gastrointestinal function
timeFrame: From date of surgery until discharge from hospital (14 days on average)
Secondary outcomes:
measure: Time until passage of stool (in days)
timeFrame: From date of surgery until discharge from hospital (14 days on average)
measure: Time until passage of flatus (in days)
timeFrame: From date of surgery until discharge from hospital (14 days on average)
measure: Time until tolerance of solid oral diet (in days)
timeFrame: From date of surgery until discharge from hospital (14 days on average)
measure: Presence of prolonged postoperative ileus
timeFrame: From date of surgery until discharge from hospital (14 days on average)
measure: Levels of serum inflammatory markers (in pg/mL)
timeFrame: 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).
measure: Length of postoperative stay (in days)
timeFrame: From date of surgery until discharge from hospital (14 days on average)
Other outcomes:
measure: Rate of gastric emptying using the 13-carbon octanoate breath test
timeFrame: This test will be undertaken on day 2 postoperatively, and will take approximately 4 hours
Locations:
city: Auckland
country: New Zealand
facility: University of Auckland
Study officials:
References:
citation: 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.