Controlled-Release Oxycodone vs. Placebo in the Treatment of Chronic Breathlessness-A Multisite Randomized Placebo Controlled Trial

Diana H Ferreira; Sandra Louw; Philip McCloud; Belinda Fazekas; Christine F McDonald; Meera R Agar; Katherine Clark; Nikki McCaffrey; Magnus Ekström; David C Currow; Australian National Palliative Care Clinical Studies Collaborative (PaCCSC)

doi:10.1016/j.jpainsymman.2019.10.017

Controlled-Release Oxycodone vs. Placebo in the Treatment of Chronic Breathlessness-A Multisite Randomized Placebo Controlled Trial

J Pain Symptom Manage. 2020 Mar;59(3):581-589. doi: 10.1016/j.jpainsymman.2019.10.017. Epub 2019 Oct 23.

Affiliations

¹ Discipline, Palliative and Supportive Services, Flinders University, Adelaide, South Australia, Australia.
² McCloud Consulting Group, Narabang Way, Belrose, New South Wales, Australia.
³ Discipline, Palliative and Supportive Services, Flinders University, Adelaide, South Australia, Australia; IMPACCT, Faculty of Health, University of Technology Sydney, Ultimo, New South Wales, Australia.
⁴ Austin Health, Heidelberg, Victoria, Australia; University of Melbourne, Parkville, Victoria, Australia.
⁵ IMPACCT, Faculty of Health, University of Technology Sydney, Ultimo, New South Wales, Australia.
⁶ Northern Sydney Local Health District, St Leonards, New South Wales, Australia; University of Sydney, Glebe, New South Wales, Australia.
⁷ Deakin Health Economics, School of Health and Social Development, Deakin University, Melbourne, Victoria, Australia.
⁸ IMPACCT, Faculty of Health, University of Technology Sydney, Ultimo, New South Wales, Australia; Department of Clinical Sciences Lund, Lund University, Faculty of Medicine, Respiratory Medicine and Allergology, Lund, Sweden.
⁹ Discipline, Palliative and Supportive Services, Flinders University, Adelaide, South Australia, Australia; IMPACCT, Faculty of Health, University of Technology Sydney, Ultimo, New South Wales, Australia. Electronic address: david.currow@uts.edu.au.

PMID: 31655189
DOI: 10.1016/j.jpainsymman.2019.10.017

Abstract

Context: Chronic breathlessness is a clinical syndrome that results in significant distress and disability. Morphine can reduce chronic breathlessness when the contributing etiologies are optimally treated.

Objectives: Does oxycodone reduce chronic breathlessness compared with placebo?

Methods: A multisite, randomized, placebo-controlled, double-blind, parallel-arm, fixed-dose trial of oral controlled-release oxycodone 15 mg (5 mg, eight hourly) or placebo (ACTRN12609000806268 at www.anzctr.org.au). As-needed immediate-release morphine (2.5 mg per dose; six and less 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 naive. The primary end point was the proportion of people with greater than 15% reduction from baseline in the intensity of breathlessness now (0-100 mm visual analogue scale) comparing arms Days 5-7. Secondary end points were average and worst breathlessness, quality of life, function, and harms.

Results: Of 157 participants randomized, 155 were included (74 oxycodone and 81 placebo), but the study did not reach target recruitment. There was difference in neither between groups for the primary outcome (P = 0.489) nor any of the prespecified secondary outcomes. Placebo participants used more as-needed morphine (mean 7.0 vs. 4.2 doses; P ≤ 0.001). Oxycodone participants reported more nausea (P < 0.001).

Conclusion: 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.

Keywords: Chronic breathlessness; effectiveness study; oxycodone; palliative care; placebo study; randomized controlled trial; symptom control.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Analgesics, Opioid* / therapeutic use
Australia
Delayed-Action Preparations
Double-Blind Method
Dyspnea* / drug therapy
Humans
Oxycodone* / therapeutic use
Quality of Life*

Substances

Analgesics, Opioid
Delayed-Action Preparations
Oxycodone

Associated data

ANZCTR/ACTRN12609000806268