Efficacy and safety of gabapentin for treatment of cough in idiopathic pulmonary fibrosis: a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Cough is common in idiopathic pulmonary fibrosis (IPF) and substantially impairs quality of life, but effective treatment options are limited. Gabapentin reduces cough in refractory chronic cough, but its efficacy and safety in IPF-related cough are uncertain. RESEARCH QUESTION: Does gabapentin improve cough in patients with IPF? STUDY DESIGN AND METHODS: This study was a randomized, double-blind, placebo-controlled clinical trial conducted at Tongji Hospital, Tongji University. Patients diagnosed with IPF according to the ATS/ERS/JRS/ALAT guidelines, with chronic cough lasting for more than 8 weeks and a cough visual analog scale (VAS) score ≥40 mm, were included. Participants were randomly assigned in a 1:1 ratio to receive either gabapentin or placebo. Gabapentin was titrated to a maximum of 900 mg/d during 12 weeks of treatment, followed by a 4-week post-treatment follow-up. The primary endpoint was the cough relief rate at T4 (end of treatment), defined as the proportion of participants achieving a reduction of at least 50% in total Cough Symptom Score (CSS) from baseline. Safety was assessed in all participants who received at least one dose of study treatment. RESULTS: Between May 1, 2021, and December 31, 2024, 72 participants were screened, of whom 68 were randomized to gabapentin or placebo. Five participants withdrew prior to study completion. At T4, the cough relief rate was higher with gabapentin than with placebo (73.5% vs 26.5%), with a placebo-adjusted absolute difference of 47.1 percentage points (95% CI, 26.1-68.0; P < 0.001). During treatment, adverse events occurred in 32.4% of participants receiving gabapentin and 8.8% receiving placebo. The most common adverse events in the gabapentin group were drowsiness, fatigue, and dizziness. INTERPRETATION: Gabapentin demonstrated significant efficacy with an acceptable safety profile in treating cough in IPF. These findings support gabapentin as a potential treatment option for IPF-related cough. CLINICAL TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (ChiCTR2100045202).