Controlled-release morphine may reduce cough frequency in IPF

Dosing in study is efficacious while limiting side effects, researchers say

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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IPF treatment | Pulmonary Fibrosis News | NP-120 findings Phase 2 trial | illustration of man coughing

Low doses of controlled-release morphine, a natural opioid derived from the opium poppy, may reduce the frequency of daytime cough in people with idiopathic pulmonary fibrosis (IPF), according to data from a Phase 2 clinical trial.

In the trial, called PACIFY COUGH (NCT04429516), patients who were experiencing persistent cough for at least eight weeks (two months) also saw their quality of life improve after being treated with morphine, but not a placebo, suggesting that morphine may be an option for palliative care.

“There is no direct evidence to guide the treatment of cough in IPF,” the researchers wrote. “The results of this trial are important for [the] almost 85% of patients with IPF who have cough and the clinicians involved in their treatment.”

Findings were detailed in the study, “Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial,” published in The Lancet Respiratory Medicine.

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IPF is a lung disease of unknown cause in which lung tissues becomes scarred and stiff over time, making it hard for patients to breathe. People with IPF often experience a persistent cough that can be distressing and for which there are no proven treatments.

Like other opioids, morphine is thought to block the cough reflex — a mechanism that causes muscles in the chest and abdomen to push air out of the lungs to force out dust or other foreign particles. However, opioids can become addictive and have serious side effects.

“Although morphine is frequently used as a palliative agent for [shortness of breath] in IPF, its effect on cough has never been tested,” the researchers wrote.

The study and its results

Here, a group of international researchers came together to test how safe low doses of controlled-release morphine are in people with IPF and how effective they are versus a placebo in reducing the frequency of daytime cough.

Controlled-release capsules do not release morphine continuously over the course of a dosing interval, which not only prolongs morphine’s action, but also keeps its levels within the therapeutic window to avoid peaks that may lead to side effects.

The trial included 31 men and 13 women, mean age 71, with a recent diagnosis of IPF. All reported a persistent cough lasting more than eight weeks.

More than half (59%) were taking antifibrotics to slow down scarring. Nineteen (43%) had acid reflux, and 13 (30%) were using proton pump inhibitors to ease acid reflux.

Patients were randomly assigned to receive oral controlled-release capsules containing 5 mg of morphine or a placebo, twice daily, for 14 days (two weeks). After a seven-day break, those who had been initially assigned to morphine switched to a placebo, and vice versa.

Daytime cough was tracked using a recording device with a microphone and sensor worn on the chest. Periods of silence and noncough sounds were removed from the recorded files using special software, and the number of coughs was manually counted.

Controlled-release morphine reduced the frequency of daytime cough by 39.4% compared with a placebo. Over the 14 days of treatment with morphine, mean daytime cough frequency dropped by 40.8% — from 21.6 to 12.8 coughs per hours. With the placebo, there was a 4.3% drop, with the mean number of coughs per hour decreasing from 21.5 to 20.6.

Treatment with controlled-release morphine also improved all cough-related patient-reported outcomes.

A larger increase in the score of the Leicester Cough Questionnaire — a cough-specific quality-of-life score that ranges from 3 to 21, with higher values indicating a better quality of life — was seen after treatment with morphine compared with a placebo (1.8 vs. 0.6 points).

According to the Global Impression of Change, which reflects a patient’s belief about the efficacy of treatment, controlled-release morphine eased symptoms of cough in 24 (56%) patients and improved overall quality of life in 14 (32%).

“The improvements in subjective and objective cough count and associated benefits in quality of life with morphine suggest that the drug offers an effective treatment option for this group of patients,” the researchers wrote.

Patients adhered well to treatment with morphine, and the most common side effects of morphine were constipation (21%) and nausea (14%). One patient experienced moderate nausea and severe hypersomnia (excessive sleepiness) and discontinued treatment.

While short-term use of morphine improved cough by 20% or more in over half of the patients in the trial, “longer term studies should be conducted to establish the durability of its effects and the impact of improving cough on disease outcomes,” the researchers wrote.