Morphine promising treatment to palliate cough in IPF patients: PACIFY COUGH study

"Low-dose controlled-release morphine significantly reduced objective cough counts over 14 days versus placebo in patients with cough related to IPF," Prof Philip L Molyneaux, Royal Brompton and Harefield Hospitals, London, UK, and colleagues reported.

Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting a cough. Currently, there are no proven treatments. Dr. Molyneaux and colleagues examined the use of low-dose controlled-release morphine compared with placebo as an antitussive therapy in patients with idiopathic pulmonary fibrosis.

For this purpose, the researchers conducted a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial (PACIFY COUGH study) in three specialist centres in the UK. Eligible patients aged 40-90 years had a diagnosis of IPF within 5 years, self-reported cough (lasting >8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher.

Patients were randomly assigned in a ratio of 1:1 to twice daily or controlled-release morphine 5 mg orally twice daily for 14 days; this was followed by crossover after a 7-day washout period. Patients were sequentially randomized to a sequence group defining the order in which morphine and placebo were to be administered, according to a computer-generated schedule.

The study's primary endpoint was the percentage change from baseline in objective awake cough frequency (coughs per h) as evaluated by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. For all patients who took at least one study drug and did not withdraw consent, the safety data were summarized.

Forty-seven participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment between Dec 17, 2020, and March 21, 2023. The mean age was 71 years, 70% were male.

The researchers revealed the following findings:

• Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L, mean predicted FVC was 82%, and mean predicted diffusion capacity of carbon monoxide was 48%.
• Of the 44 patients who were randomized, 43 completed morphine treatment and 41 completed placebo treatment.
• In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% compared with placebo.
• There was a reduction in mean daytime cough frequency from 21·6 coughs per hour at baseline to 12·8 coughs per h with morphine, whereas cough rates did not change with placebo (21·5 coughs per h to 20·6 coughs per h).
• Treatment adherence was 98% in the morphine group and 98% in the placebo group.
• Adverse events were observed in 40% of participants in the morphine group and six 14% of patients in the placebo group.
• The main side effects of morphine were nausea (14%) and constipation (21%).
• One serious adverse event (death) occurred in the placebo group.

"Treatment with low dose controlled-release morphine significantly improved subjective and objective cough measures in patients with IPF-associated cough," the researchers wrote.

"These findings merit its short-term use in clinical practice, given the negative effects of cough in individuals with IPF," they concluded. "Longer-term studies should be the focus of future research."

Reference:

Wu, Z., Spencer, L. G., Banya, W., Westoby, J., Tudor, V. A., Rivera-Ortega, P., Chaudhuri, N., Jakupovic, I., Patel, B., Thillai, M., West, A., Wijsenbeek, M., Maher, T. M., Smith, J. A., & Molyneaux, P. L. (2024). Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): A prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial. The Lancet Respiratory Medicine. https://doi.org/10.1016/S2213-2600(23)00432-0