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Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea

BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7414.523 (Published 04 September 2003) Cite this as: BMJ 2003;327:523
  1. Amy P Abernethy, research fellow11,
  2. David C Currow (david.currow{at}rgh.sa.gov.au), professor1,
  3. Peter Frith, consultant3,
  4. Belinda S Fazekas, research manager2,
  5. Annie McHugh, research nurse2,
  6. Chuong Bui, consultant4
  1. 1Department of Palliative and Supportive Services, Division of Medicine, Flinders University of South Australia, Bedford Park, South Australia 5042, Australia
  2. 2Southern Adelaide Palliative Services, Repatriation General Hospital, Daw Park, South Australia 5042, Australia
  3. 3Respiratory Medicine Department, Repatriation General Hospital
  4. 4Department of Nuclear Medicine, Nepean Hospital, Kingswood, New South Wales 2747, Australia
  1. Correspondence to: D C Currow

    Abstract

    Objective To determine the efficacy of oral morphine in relieving the sensation of breathlessness in patients in whom the underlying aetiology is maximally treated.

    Design Randomised, double blind, placebo controlled crossover study.

    Setting Four outpatient clinics at a hospital in South Australia.

    Participants 48 participants who had not previously been treated with opioids (mean age 76, SD 5) with predominantly chronic obstructive pulmonary disease (42, 88%) were randomised to four days of 20 mg oral morphine with sustained release followed by four days of identically formulated placebo, or vice versa. Laxatives were provided as needed.

    Main outcome measures Dyspnoea in the morning and evening as shown on a 100 mm visual analogue scale, quality of sleep, wellbeing, performance on physical exertion, and side effects as measured at the end of the four day treatment period.

    Results 38 participants completed the study; three withdrew because of definite and two because of possible side effects of morphine (nausea, vomiting, and sedation). Participants reported significantly different dyspnoea scores when treated with morphine: an improvement of 6.6 mm (95% confidence interval 1.6 mm to 11.6 mm) in the morning and of 9.5 mm (3.0 mm to 16.1 mm) in the evening (P = 0.011 and P = 0.006, respectively). During the period in which they were taking morphine participants also reported better sleep (P = 0.039). More participants reported distressing constipation while taking morphine (9 v 1, P = 0.021) in spite of using laxatives. All other side effects were not significantly worse with morphine, although the study was not powered to address side effects.

    Conclusions Sustained release, oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting.

    Footnotes

    • Contributors APA was responsible for study design; obtaining funding; logistic, administrative, and technical support; recruitment of participants; collection, assembly, and analysis of data; statistical expertise; and data interpretation; drafting, critical revision, and final approval of the article. DCC was responsible for conception and design of the study; logistic, administrative, and technical support; analysis and interpretation of data; and drafting, critical revision, and final approval of the article. PF was responsible for study design; obtaining funding; logistic support; recruitment of participants; data interpretation; and drafting, critical revision, and final approval of the article. BSF was responsible for logistic, administrative, and technical support; recruitment of participants; collection, assembly, and analysis of data; and drafting, critical revision, and final approval of the article. AM was responsible for logistic and technical support; recruitment of participants, collection, assembly, and interpretation of data; and drafting, critical revision, and final approval of the article. CB was responsible for conception and design of the study and critical revision and final approval of the article. APA is the guarantor.

    • Funding Funds for the conduct of the study were provided by the Flinders Medical Centre Foundation of Bedford Park, South Australia, Australia ($A6000; €3500; £2400). APA's salary was provided through a clinical scientist development award from the Doris Duke Charitable Foundation of New York, New York, United States.

    • Competing interests Placebo capsules of identical appearance were provided by the company that manufactures sustained release morphine sulphate (Kapanol, Glaxo Wellcome Australia); no direct funds were provided by the drug company.

    • Ethical approval The study was approved by the local institutional research and ethics committee, and the trial was registered with the Australian therapeutic goods administration.

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