A randomized, double-blind, placebo-controlled, dose escalation study evaluating the efficacy of duloxetine and amitriptyline in interstiital lung disease-related cough (macs-2)

SESSION TITLE: Cough: Nothing to Sneeze About SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/10/2023 12:00 pm - 12:45 pm PURPOSE: Guidelines recommend the use of neuromodulatory medications for refractory interstitial lung disease (ILD)-related cough. However, there is limited evidence to support this recommendation. METHODS: MACS-2 (Mayo Acoustic Cough Study-2) is an investigator-initiated randomized, double-blind, placebo-controlled, parallel-arm, dose escalation study of duloxetine and amitriptyline in subjects with ILD-related cough over 2 consecutive 4-week treatment cycles. Patients are randomized 1:1:1:1:1 to one of five treatment arms. Arm 1: duloxetine 30mg X 4 weeks followed by duloxetine 30mg plus placebo pill x 4 weeks; Arm 2: duloxetine 30mg followed by duloxetine 30mg + 30mg; Arm 3: amitriptyline 25mg followed by amitriptyline 25mg plus placebo pill; Arm 4: amitriptyline 25mg followed by amitriptyline 25mg + 25mg; and Arm 5: placebo x 4 weeks followed by 2 placebo pills for 4 weeks. Patients are then unblinded and followed clinically for a total of 12 months with acoustic cough monitoring at 3 monthly intervals. The primary outcome is reduction in awake objective cough frequency determined by the Leicester Cough Monitor at 4 and 8 weeks. Secondary endpoints include reduction in 24-hour objective cough frequency, reduction in subjective scores of cough severity and improvement in cough-specific quality of life. RESULTS: A total of 8 patients have been recruited (50 % females) with median age of 71 (range 62 to 78) years and median duration of cough of 6.5 (range 2 to 18) years. Underlying ILD was UIP/IPF in 3 (37.5%), NSIP in 2 (25%), CTD-ILD in 1 (12.5%), pleuroparenchymal fibroelastosis in 1 (12.5%) and hypersensitivity pneumonitis in 1 (12.5%). ILD was biopsy proven in 3 (37.5%). Associated comorbidities include gastroesophageal reflux disease in 4 (50%) and depression in 1 (12.5%). Previous treatments include proton pump inhibitors in 5 (62.5%), over the counter antitussives in 2 (25%), opiates in 2 (25%), inhaled medications in 2 (25%), neuromodulatory agents in 1 (12.5%), and nasal steroids in 1 (12.5%). Active treatment for ILD at time of enrollment included antifibrotics in 3 (37.5%), steroids in 3 (37.5%), methotrexate in 2 (25%), while 2 patients were not receiving ILD-directed therapies. Baseline total coughs in 24 hours, awake coughs and night coughs were 894.5 (range 87 to 2330), 697 (range 408 to 1477), and 135 (range 0 to 615) coughs, respectively. Comparison of baseline to follow up cough counts is in progress. One patient was randomized to arm 1, 2 to arm 2, 2 to arm 3, 1 to arm 4, 1 to arm 5, and one patient was still undergoing intervention at the time of analysis. One patient withdrew consent due to lack of efficacy who was randomized to arm 2. CONCLUSIONS: We provide preliminary data comparing the efficacy of duloxetine and amitriptyline vs. placebo in the treatment of ILD-cough using objective (numeric) cough counts. Patients continue to receive follow up with acoustic cough monitoring every 3 months for a total of 12 months after completion of the 8-week blinded portion of the trial. CLINICAL IMPLICATIONS: This study will help evaluate the role of amitryptilne and duloxetine for the managemnt of ILD-related cough DISCLOSURES: No relevant relationships by Joshika Agarwal No relevant relationships by Vibhor Ahluwalia No relevant relationships by Vaibhav Ahluwalia No relevant relationships by Sumera Ahmad No relevant relationships by Hasan Ahmad Hasan Albitar No relevant relationships by Shivam Damani No relevant relationships by Sue Donlinger No relevant relationships by Sue Donlinger No relevant relationships by Ashley Egan No relevant relationships by Sumedh Hoskote No relevant relationships by Sumedh Hoskote No relevant relationships by Vivek Iyer No relevant relationships by Kinnera Jalagam No relevant relationships by Jeremiah Joyce monograph relationship with BMJ Please note: $1-$1000 by Karina Keogh, value=Honoraria Site PI for pharmaceutical trial relationship with AstraZeneca Please note: 2022 by Karina Keogh, value=Site PI for pharmaceutical tri Educational grant relationship with GSK/Potomac Center for Medical Education (PCME), Please note: 2019-2020 by Karina Keogh, value=Travel No relevant relationships by Augustine Lee No relevant relationships by Kaiser Lim No relevant relationships by Ashokakumar Patel No relevant relationships by Shivaram Poigai Arunachalam No relevant relationships by Nanditha Venkatesan No relevant relationships by Kathleen Yost