A Comparison of Targinact vs. Oxycodone on Gut Function After Colorectal Surgery

Postoperative Pain Clinical Trial

— TACS  

Official title:

A Randomized Blinded Pilot Study to Compare Targinact vs. Oxycodone in Early Return of Gastrointestinal Function After Colorectal Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02109640
• Other study ID #: 2013-005327-16
• Status: Completed
• Phase: Phase 3
• First received: April 3, 2014
• Last updated: November 10, 2015
• Start date: October 2014
• Est. completion date: August 2015

Study information

• Verified date: November 2015
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health Service
• Study type: Interventional

Clinical Trial Summary

Two key requirements for discharge from hospital after major abdominal surgery are adequate oral analgesia and resumption of oral nutrition. Up to 40% of patients suffer delayed discharge after abdominal surgery due to delayed return of gut function, manifesting as nausea, vomiting, constipation and abdominal distension. Opiates and their derivatives are the mainstay of postoperative analgesic regimens after abdominal surgery and are highly effective in achieving adequate pain control. However, opioids cause impaired gut function by reducing normal forward propulsion and increasing gut spasm. Opioid receptor blockers such as Alvimopan counteract these effects and can accelerate postoperative gut recovery but are expensive and cause cardiac complications; alternative painkillers such as non-steroidal anti-inflammatories are less effective than opioids and have been linked with increased risk of anastomotic leaks.

Targinact is a combination of prolonged release opioid analgesic (oxycodone hydrochloride) and naloxone hydrochloride (an opioid receptor blocker). The formulation of the product confines the naloxone action to the gut to reduce the unwanted side-effects on gut function. Targinact has been shown in patients with chronic severe pain to provide comparable analgesia to other opioid analgesics whilst reducing the unwanted side-effect of constipation.

The Investigators wish to test the hypothesis that Targinact will provide adequate analgesia after colonic resection with reduced postoperative gastrointestinal dysfunction. The surgical procedure chosen to test this hypothesis is laparoscopic segmental colectomy, a consistently reproducible intervention with a postoperative gut dysfunction rate of up to 40% (prospective data from the Edinburgh Colorectal Unit). The main outcome of the study will be return of normal gut function at the time of planned discharge (Day 3).

Description:

Study hypothesis: Targinact is effective as oral analgesia after major colorectal surgery and is associated with less gut dysfunction than Oxycodone.

Up to 40% of patients suffer delayed return of gut function after elective colorectal surgery, leading to prolonged hospital stay and higher inpatient costs. For the patient, this is characterised by a variety of symptoms including nausea and vomiting, delayed ability to regain normal oral intake, abdominal discomfort/distension and constipation. Although post-operative gut dysfunction tends to resolve spontaneously in 3-7 days, both symptoms and supportive treatment (nasogastric tube insertion, repeated venous cannulation for intravenous fluid administration etc) are unpleasant.

Elective colorectal surgery is a common hospital intervention hence a reduction in the prevalence of post-operative gut dysfunction would be expected to benefit a large number of patients with attendant reduction in health service costs. The objective aligns well with the current national dissemination of Enhanced Recovery after Surgery programmes by the UK Department of Health and Scottish Government.

Post-operative gut dysfunction is multifactorial. Opioid analgesics are contributory and all Enhanced Recovery after Surgery (ERAS) programmes emphasise strategies to minimise systemic opioid use (eg using regional or local anaesthetic techniques).

Targinact has not been evaluated in the setting of short-term post operative analgesia in colorectal surgery but offers the potential to achieve effective analgesia with a lower incidence of gut dysfunction and therefore an important role within the ERAS program after colorectal surgery. Oxycodone is currently the oral opioid analgesic of choice in our unit and most patients are prescribed a combination of oxycodone and oxynorm as step-down analgesia following cessation of systemic or epidural analgesia, often in combination with fentanyl patches.

Data will be collected from patient hospital records and questionnaires administered by the principal investigator and research study nurse.

Multiple measures will be employed to record both presence of good function and absence of dysfunction.

• Time to first flatus

• Time to first bowel movement

• Time from surgery to cessation of iv fluids

• Total dose of rescue antiemetic (protocol ondansetron not included)

• Reinstitution of iv fluids (Y/N) Quantity of laxative used

• Measurement of oral nutritional intake:

Preoperative intake will be recorded by means of a recall diary. Postoperative oral intake will be recorded by the participant using a food diary for 7 days from the date of surgery. Energy intake will then be estimated using CompEat Pro® forWindows® (Nutrition Systems, Banbury, UK). Time to attain and maintain 80% of normal solid food intake and the percentage Recommended Nutritional Intake (RNI) achieved on days 1-3 and days 5-7 after surgery will be used in comparisons between study groups.

• Validated nausea and vomiting score (Miles and Wengritzky)

• Presence of abdominal distension (Y/N)

• 13C Stable Isotope Gastric Empyting Breath Test to measure gastric motility on the second postoperative morning. The technique has been previously used in the Edinburgh Department of Surgery and validated to be a reproducible and accurate measurement of upper GI motility.

Additional data to be recorded:

• Patient demographics, co morbidity, regular medications

• Pre op bowel function questionnaire

• Postoperative nausea and vomiting prediction data (Apfel score)

• Day 3 achievement of discharge criteria (pain controlled by oral analgesia, tolerating adequate oral diet and fluids, independently mobile and willing to go home) Y/N

• 30-day/Inpatient mortality

• Duration of hospital admission

• Complications (recorded by organ system and severity as assessed by Clavien/Dindo scale)

• Unscheduled readmissions to hospital within 30 days of discharge

• Patient-reported outcome questionnaire

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients scheduled for elective laparoscopic segmental colectomy at the Colorectal Surgery Unit, Western General Hospital, Edinburgh.

Exclusion Criteria:

• Pregnancy Age <18 years Patients lacking capacity to give informed consent. Severe liver dysfunction (Child's A or greater) Patients participating in another therapeutic clinical trial Contraindication to oxycodone, naloxone or Targinact Pre-existing dependence on opioid analgesia (current medications will be checked prior to discussing consent) Pre-existing use of opioid analgesia for chronic pain (current medications will be checked prior to discussing consent) Patients with rectal cancer Plan to form any stoma during procedure

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Nausea and Vomiting
• Postoperative Pain

Intervention

Drug:
• Targinact
Post-operative analgesia
• Oxycodone
Postoperative analgesia

Procedure:
• Laparoscopic segmental colectomy

Locations

Country	Name	City	State
United Kingdom	Western General Hospital	Edinburgh

Sponsors (1)

Lead Sponsor	Collaborator
University of Edinburgh

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

Hendry PO, Hausel J, Nygren J, Lassen K, Dejong CH, Ljungqvist O, Fearon KC; Enhanced Recovery After Surgery Study Group. Determinants of outcome after colorectal resection within an enhanced recovery programme. Br J Surg. 2009 Feb;96(2):197-205. doi: 10.1002/bjs.6445. — View Citation

Lassen K, Soop M, Nygren J, Cox PB, Hendry PO, Spies C, von Meyenfeldt MF, Fearon KC, Revhaug A, Norderval S, Ljungqvist O, Lobo DN, Dejong CH; Enhanced Recovery After Surgery (ERAS) Group. Consensus review of optimal perioperative care in colorectal surgery: Enhanced Recovery After Surgery (ERAS) Group recommendations. Arch Surg. 2009 Oct;144(10):961-9. doi: 10.1001/archsurg.2009.170. Review. — View Citation

Simpson K, Leyendecker P, Hopp M, Müller-Lissner S, Löwenstein O, De Andrés J, Troy Ferrarons J, Bosse B, Krain B, Nichols T, Kremers W, Reimer K. Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain. Curr Med Res Opin. 2008 Dec;24(12):3503-12. doi: 10.1185/03007990802584454 . — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of postoperative gut dysfunction	25% reduction in the proportion of participants with gut dysfunction, defined as the presence of any of the following sufficient to delay discharge on the 3rd postoperative day: nausea, vomiting, intolerance of oral intake or constipation.	Day 3 post-op	No
Secondary	Pain control	Total quantity of Morphine used over standard analgesia protocol	Participants will be followed for the duration of hospital stay, an expected average of 5 days	No
Secondary	Oral analgesia use	Total dose of oral Oxycodone or Targinact until discontinued by the participant/discharged from hospital	Participants will be followed for the duration of hospital stay, an expected average of 5 days	No
Secondary	Pain scores	Pain scores measured daily using Overall Benefit of Analgesia Score (OBAS)	Participants will be followed for the duration of hospital stay, an expected average of 5 days	No