title: Randomized open-label phase II study comparing oxycodone-naloxone with oxycodone in early return of gastrointestinal function after laparoscopic colorectal surgery.
abstract: BACKGROUND
  Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection.
  
  
  METHODS
  In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance. Secondary endpoints included a composite endpoint of gut function (tolerance of solid food, low nausea/vomiting score, passage of flatus or faeces).
  
  
  RESULTS
  Eighty-two patients were screened and 62 randomized (76 per cent); the attrition rate was 19 per cent (12 of 62), leaving 50 patients who received the allocated intervention with 100 per cent follow-up and retention (modified intention-to-treat cohort). Protocol compliance was more than 90 per cent. Return of gut function by day 3 was similar in the two groups: 13 (48 per cent) of 27 in the oxycodone-naloxone group and 15 (65 per cent) of 23 in the control group (95 per cent c.i. for difference -10·0 to 40·7 per cent; P = 0·264). However, patients in the oxycodone-naloxone group had a shorter time to first bowel movement (mean(s.d.) 87(38) h versus 111(37) h in the control group; 95 per cent c.i. for difference 2·3 to 45·4 h, P = 0·031) and reduced total (oral plus parenteral) opioid consumption (mean(s.d.) 78(36) versus 94(56) mg respectively; 95 per cent c.i. for difference -10·2 to 42·8 mg, P = 0·222).
  
  
  CONCLUSIONS
  High participation, retention and protocol compliance confirmed feasibility. Potential benefits of oxycodone-naloxone in reducing time to bowel movement and total opioid consumption could be tested in a randomized trial. Registration number: NCT02109640 (https://www.clinicaltrials.gov/).
authors.affiliation: University of Edinburgh Academic Coloproctology, Edinburgh, UK.
authors.forename: F
authors.initials: F
authors.lastname: Creamer
authors.affiliation: University of Edinburgh Academic Coloproctology, Edinburgh, UK.
authors.forename: A
authors.initials: A
authors.lastname: Balfour
authors.affiliation: Department of Anaesthesia, Western General Hospital, Edinburgh, UK.
authors.forename: S
authors.initials: S
authors.lastname: Nimmo
authors.affiliation: Department of Anaesthesia, Western General Hospital, Edinburgh, UK.
authors.forename: I
authors.initials: I
authors.lastname: Foo
authors.affiliation: Centre for Healthcare Randomised Trials, Health Services Research Unit, Foresterhill, Aberdeen, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Norrie
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Williams
authors.affiliation: University of Edinburgh Academic Coloproctology, Edinburgh, UK.
authors.forename: K C
authors.initials: KC
authors.lastname: Fearon
authors.affiliation: University of Edinburgh Academic Coloproctology, Edinburgh, UK.
authors.forename: H M
authors.initials: HM
authors.lastname: Paterson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D003082:Colectomy; D003672:Defecation; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004338:Drug Combinations; D004363:Drug Utilization; D004435:Eating; D005240:Feasibility Studies; D005260:Female; D005414:Flatulence; D006801:Humans; D010535:Laparoscopy; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000627:therapeutic use*; D010098:Oxycodone / Q000627:therapeutic use*; D010149:Postoperative Pain / Q000517:prevention & control; D010349:Patient Compliance; D010865:Pilot Projects; D011229:Preanesthetic Medication; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; C557247:oxycodone naloxone combination; D009270:Naloxone; D010098:Oxycodone