Controlled-release oxycodone versus placebo in the treatment of chronic breathlessness - a multi-site randomised placebo controlled trial.

Chronic breathlessness is a clinical syndrome that results in significant distress and disability. Morphine can reduce chronic breathlessness when the contributing aetiologies are optimally treated.Does oxycodone reduce chronic breathlessness compared with placebo?A multi-site, randomised, placebo-controlled, double-blind, parallel-arm, fixed-dose trial of oral controlled-release oxycodone 15mg (5 mg 8 hourly) or placebo (ACTRN12609000806268 at www.anzctr.org.au). 'As needed' immediate-release morphine (2.5mg per dose; ≤6 doses/day) was available for both arms as required by one ethics committee overseeing the trial.Recruitment occurred from 2010 to 2014 in 14 inpatient and outpatient respiratory, cardiology and palliative care services across Australia. Participants were adults, with chronic breathlessness (modified Medical Research Council Scale 3 or 4), who were opioid naïve. The primary endpoint was the proportion of people with >15% reduction from baseline in the intensity of breathlessness now (0-100 mm visual analogue scale) comparing arms days 5-7. Secondary endpoints were 'average' and 'worst' breathlessness; quality of life; function; and harms.Of 157 participants randomised, 155 were included (74 oxycodone, 81 placebo), but the study did not reach target recruitment. There was no difference between groups for the primary outcome (p=0.489) nor any of the pre-specified secondary outcomes. Placebo participants used more 'as needed' morphine (mean 7.0 versus 4.2 doses; p≤0.001). Oxycodone participants reported more nausea (p<0.001).There was no signal of benefit from oxycodone over placebo. Future research should focus on investigating the existence of an opioid class effect on the reduction of chronic breathlessness.