Low dose morphine lowers objective cough frequency in IPF

Key takeaways:

• Patients with idiopathic pulmonary fibrosis coughed fewer times per hour after receiving a 14-day morphine course.
• Health-related quality of life also improved with this drug.

Receiving a 5 mg dose of controlled-release morphine twice daily for 14 days lowered objective cough frequency in patients with idiopathic pulmonary fibrosis, according to results published in The Lancet Respiratory Medicine.

“This multicenter study shows that low-dose controlled-release morphine is effective in reducing awake cough frequency and improving quality of life in participants with significant IPF-related cough,” Zhe Wu, MD, of the National Heart and Lung Institute at Imperial College London, and colleagues wrote.

In a prospective, multicenter, randomized, double-blind, placebo-controlled, two-way crossover, phase 2 trial (PACIFY COUGH), Wu and colleagues analyzed 44 adults (mean age, 71 years; 70% men) with idiopathic pulmonary fibrosis (IPF)-related cough to determine if 5 mg of controlled-release morphine twice daily for 14 days lowers objective awake cough frequency compared with placebo.

To be included, patients needed to have a self-reported cough that lasted more than 8 weeks and a 30 mm or higher cough VAS score in addition to IPF.

Initially, half of the total cohort received morphine and half received placebo for 14 days. Once this period ended, there was a 7-day washout period and then patients received the opposite treatment.

Researchers used objective digital cough monitoring to evaluate the percentage change in objective awake cough frequency between baseline and day 14 of each treatment.

Baseline measures of lung function, including mean FVC (2.7 L), mean predicted FVC (82%) and mean predicted diffusion capacity of carbon monoxide (48%), demonstrated moderate impairment, according to researchers.

Prior to the first treatment period, one patient withdrew consent. By the end of the study, all 43 patients completed the morphine treatment period, whereas only 41 completed the placebo treatment period because one patient died and the other withdrew consent. Researchers attributed this patient’s death to “underlying IPF disease trajectory.”

Treatment adherence was high in both groups (98%).

When placed against placebo, researchers found a 39.4% drop (95% CI, –54.4 to –19.4) in objective awake cough frequency with low dose controlled-release morphine.

From baseline to day 14 of morphine treatment, the number of coughs per hour fell from 21.6 to 12.8. Researchers did not find a significant reduction in the number of coughs per hour from baseline to day 14 of placebo treatment (21.5 to 20.6).

In addition to cough frequency, a 14-day course of morphine also improved baseline cough VAS (–16.1 mm; 95% CI, –22.3 to –9.9) and Leicester Cough Questionnaire scores (1.8 points; 95% CI, 0.9-2.8).

Researchers further evaluated how symptoms and health-related quality of life changed from baseline to day 14 of morphine treatment through the Living with IPF (L-IPF) questionnaire. In this questionnaire, higher scores indicate more impairment.

For the L-IPF impacts score, patients are asked to consider symptoms from the past 7 days, and this score significantly decreased by 5.2 points (95% CI, –9.9 to –0.4) on day 14. Similarly, the total L-IPF symptoms score based on symptoms from the past 24 hours went down by 5.2 points (95% CI, –8.9 to –1.4).

Within the L-IPF total symptoms score, researchers found a significant score decrease from baseline to day 14 of morphine treatment in the cough domain (–10.8 points; 95% CI, –16.9 to –4.8) but not in the dyspnea or energy domains. Anxiety and depression, assessed through the Hospital and Depression Scale, also did not significantly change after morphine treatment.

Notably, safety data differed between the two groups.

More patients experienced an adverse event during morphine treatment than placebo treatment (17 out of 43 patients vs. 6 out of 42 patients), and frequently reported negative effects from the drug included constipation (n = 9) and nausea (n = 6).

“Given the negative effects of cough in individuals with IPF, these findings merit its short-term use in clinical practice,” Wu and colleagues wrote. “Longer term studies should be the focus of future research.”