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

NCT02109640 | Completed Phase 3 Results DMC

• 1 other identifier: 2013-005327-16
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Postoperative Pain; Postoperative Nausea and Vomiting

Keywords

Colorectal; Surgery; Laparoscopic; Analgesia; Enhanced Recovery; Targinact

Outcome Measures

Primary Outcomes (1)

• Prevalence of Postoperative Gut Dysfunction

  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

Secondary Outcomes (2)

• Total Opioid Analgesia Consumption

  Total postoperative period of analgesic consumption, an average of 1 week

• Pain Scores

  Postoperative day 3

Study Arms (2)

Targinact

EXPERIMENTAL

Oral Targinact 10-20mg bd following laparoscopic segmental colectomy

Drug: Targinact; Procedure: Laparoscopic segmental colectomy

Oxycodone

ACTIVE COMPARATOR

Oral oxycodone 10-20mg bd following laparoscopic segmental colectomy

Drug: Oxycodone; Procedure: Laparoscopic segmental colectomy

Interventions

Targinact DRUG

Post-operative analgesia

Also known as: Oxycodone-Naloxone

Targinact

Oxycodone DRUG

Postoperative analgesia

Oxycodone

Laparoscopic segmental colectomy PROCEDURE

Oxycodone; Targinact

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Edinburgh: lead

Study Sites (1)

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 19841366 BACKGROUND

• 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.

  PMID: 19160347 BACKGROUND

• Simpson K, Leyendecker P, Hopp M, Muller-Lissner S, Lowenstein O, De Andres 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.

  PMID: 19032132 BACKGROUND

• Creamer F, Balfour A, Nimmo S, Foo I, Norrie JD, Williams LJ, Fearon KC, Paterson HM. Randomized open-label phase II study comparing oxycodone-naloxone with oxycodone in early return of gastrointestinal function after laparoscopic colorectal surgery. Br J Surg. 2017 Jan;104(1):42-51. doi: 10.1002/bjs.10322. Epub 2016 Oct 20.

  PMID: 27762434 DERIVED

MeSH Terms

Conditions

Pain, Postoperative; Postoperative Nausea and Vomiting; Agnosia

Interventions

oxycodone naloxone combination; Oxycodone

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Nausea; Signs and Symptoms, Digestive; Vomiting; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Hugh M Paterson
• Organization: University of Edinburgh

hugh.paterson@ed.ac.uk

44 131 537 1000

Study Officials

• Hugh M Paterson, MD FRCS

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2014
• First Posted: April 10, 2014
• Study Start: October 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: March 29, 2017
• Results First Posted: March 29, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)