@article{Molyneaux:2026:10.1001/jama.2025.26179,
author = {Molyneaux, PL and Mogulkoc, N and Gunen, H and Doboszynska, A and Kreuter, M and Neustifter, B and Mathur, V and Cassella, J and CORAL, Study Group},
doi = {10.1001/jama.2025.26179},
journal = {JAMA},
title = {Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial.},
url = {http://dx.doi.org/10.1001/jama.2025.26179},
year = {2026}
}

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TY  - JOUR
AB  - IMPORTANCE: For patients with idiopathic pulmonary fibrosis (IPF), cough impairs quality of life; effective treatments for IPF-associated cough are needed. OBJECTIVE: To determine if nalbuphine extended release (ER), a κ opioid receptor agonist and μ-opioid receptor antagonist, decreases cough compared with placebo in patients with IPF-associated cough. DESIGN, SETTING, AND PARTICIPANTS: In this randomized, double-blind, placebo-controlled phase 2b trial conducted at 52 sites in 10 countries, patients with IPF, chronic cough for at least 8 weeks, and a Cough Severity Numerical Rating Scale (0, no cough; 10, worst possible cough) score of 4 or higher were enrolled from February 2024 to February 2025, with last follow-up in April 2025. Statistical analyses were conducted from May to August 2025. INTERVENTION: Patients were randomized 1:1:1:1 to receive nalbuphine ER at doses of 27 mg, 54 mg, or 108 mg or placebo twice daily for 6 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the relative change from baseline in 24-hour cough frequency (coughs/h), measured with a digital cough monitor, for nalbuphine ER compared with placebo at week 6. The key secondary outcome was the relative change from baseline in the patient-reported cough frequency (Evaluating Respiratory Symptoms in IPF cough subscale; scores range from 0-4, lower scores indicate lesser cough frequency) at week 6. RESULTS: Of the 223 patients screened, 165 were randomized (42, 43, 40, and 40 to receive nalbuphine ER 27 mg, 54 mg, and 108 mg, and placebo, respectively) and 160 were included in the primary analysis (median age, 71 [range, 51-85] years; 28.5% female). The baseline mean (SD) cough count was 28.3 (27.4) coughs/h. In the nalbuphine ER 27 mg, 54 mg, and 108 mg twice-daily groups, the mean relative decrease in the cough count and the absolute decrease in coughs/h were 47.9% (from 24.6 to 11.9; P = .008), 53.4% (from 28.0 to 14.9; P < .001), and 60.2%
AU  - Molyneaux,PL
AU  - Mogulkoc,N
AU  - Gunen,H
AU  - Doboszynska,A
AU  - Kreuter,M
AU  - Neustifter,B
AU  - Mathur,V
AU  - Cassella,J
AU  - CORAL,Study Group
DO  - 10.1001/jama.2025.26179
PY  - 2026///
TI  - Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial.
T2  - JAMA
UR  - http://dx.doi.org/10.1001/jama.2025.26179
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41569557
ER  - 

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