Extended-Release Morphine for Chronic Breathlessness in Pulmonary Arterial Hypertension—A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

• Context: Pulmonary arterial hypertension (PAH) affects people of all ages and is associated with poor prognosis. Chronic breathlessness affects almost all people with PAH. Objectives: This randomized, placebo-controlled, double-blind, crossover study aimed to evaluate the effects of regular, low-dose, extended-release (ER) morphine for PAH-associated chronic breathlessness. Methods: Participants with PAH-associated chronic breathlessness were randomized to 1) seven days of ER morphine 20 mg, 2) seven-day washout, and 3) seven days of identically looking placebo, or vice versa. Primary end points were breathlessness “right now”—morning and evening—measured with a Visual Analogue Scale. Secondary end points included additional breathlessness measures, quality of life, function, harms, and blinded treatment preference (ACTRN12609000209291). Results: Within a period of seven years, 50 patients were assessed in detail and 23 (46%) were randomized (despite broad eligibility criteria). Four participants withdrew while taking morphine. Nineteen participants completed the study. Breathlessness “right now” was higher on morphine compared with placebo both for morning [mean (M) ± SD 31.7 ± 25 mm vs. 26.9 ± 22 mm; effect size (80% CI) = −0.22 (−0.6 to 0.2)] and evening [(M ± SD 33.5 ± 28 mm vs. 25.6 ± 21 mm; effect size (80% CI) = −0.33 (−0.8 to 0.1)]. All secondary measures of breathlessness were higher with morphine as were nausea and constipation. Conclusion: This study does not support a Phase III study of ER morphine for people with PAH-associated chronic breathlessness. Recruiting to the target sample size was difficult, the direction of effect in every measure of breathlessness favored placebo and morphine generated more harms.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

Nyckelord

Chronic breathlessness

effectiveness study

morphine

pulmonary arterial hypertension

randomized controlled trial

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art (ämneskategori)

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