Oral Sustained-Release Morphine May Improve Moderate, Severe Breathlessness in COPD

The use of regular, low-dose, oral sustained-release morphine for 4 weeks in patients with chronic obstructive pulmonary disease (COPD) and moderate to very severe breathlessness has been shown to improve disease-specific health status, with no effect on arterial partial pressure of carbon dioxide (PaCO₂) or serious adverse events.

Researchers conducted a randomized, double-blind, placebo-controlled study (Morphine for Treatment of Dyspnea in Patients With COPD [MORDYC]; ClinicalTrials.gov identifier: NCT02429050) and the results were published in JAMA Internal Medicine.

Investigators sought to evaluate the effects of using regular, low-dose, oral sustained-release morphine on patients’ disease-specific health status (ie, COPD Assessment Test [CAT]), breathlessness, and respiratory outcomes. All study participants were randomly assigned to 1 of 2 treatment groups: regular, oral sustained-release morphine 10 mg or placebo twice daily for a period of 4 weeks, with the possibility of increasing the dosing to 3 times daily after 1 or 2 weeks.

Patients were enrolled in the MORDYC study between November 1, 2016, and

January 24, 2019. Following completion of a pulmonary rehabilitation program, the participants were recruited from a pulmonary rehabilitation center and 2 general hospitals. Those outpatients who had COPD and moderate to very severe breathlessness of grades 2 to 4, per modified Medical Research Council (mMRC), despite optimal pharmacologic and nonpharmacologic therapy, were included in the study.

After screening, a total of 111 of the 124 eligible participants were analyzed. The mean participant age was 65.4±8.0 years and 54% were men. The difference in CAT scores was 2.18 points lower in the morphine group compared with the placebo group, which was statistically significant (95% CI, -4.14 to -0.22 points; P =.03). In the subgroup of patients with mMRC grades 3 to 4, the difference between the 2 treatment groups was not statistically significant (-1.17 points; 95% CI, -4.17 to 1.84 points; P =.44).

With respect to change in PaCO₂, no significant differences were shown between the 2 groups (1.19 mm Hg higher in the morphine arm; 95% CI, -2.70 to 5.07 mm Hg; P =.55). Additionally, the subgroup of individuals with mMRC grades 3 to 4 demonstrated no clinically relevant or significant differences in PaCO₂ (1.84 mm Hg; 95% CI, -4.95 to

8.64 mm Hg; P =.59). Although breathlessness remained unchanged, the worst breathlessness improved significantly in those participants with mMRC grades 3 to 4 (1.33 points lower in the morphine group; 95% CI, -2.50 to -0.16; P =.03).

Overall, 9% (5 of 54) of the participants treated with morphine and 2% (1 of 57) of the participants given placebo withdrew from the study because of adverse events. There were no morphine-related deaths or hospital admissions reported.

The investigators concluded that their findings demonstrate a role for morphine in the palliative treatment of chronic breathlessness in patients with COPD. Additional studies with >4 weeks of follow-up are warranted to evaluate the long-term effects and safety of morphine in this patient population.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Verberkt CA, van den Beuken-van Everdingen MHJ, Schols JMGA, Hameleers N, Wouters EFM, Janssen DJA. Effect of sustained-release morphine for refractory breathlessness in chronic obstructive pulmonary disease on health status: a randomized clinical trial. JAMA Intern Med. Published online August 17, 2020. doi:10.1001/jamainternmed.2020.3134