Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility)

Abstract

New treatments are required for severe breathlessness in advanced disease. We conducted a randomised feasibility trial of mirtazapine over 28 days in adults with a modified medical research council breathlessness scale score ≥3. Sixty-four patients were randomised (409 screened), achieving our primary feasibility endpoint of recruitment. Most patients had COPD or interstitial lung disease; 52 (81%) completed the trial. There were no differences between placebo and mirtazapine in tolerability or safety, and blinding was maintained. Worst breathlessness ratings at day 28 (primary clinical activity endpoint) were, 7.1 (SD 2.3, placebo) and 6.3 (SD 1.8, mirtazapine). A phase III trial of mirtazapine is indicated. Trial registration: ISRCTN 32236160; European Clinical Trials Database (EudraCT no: 2015-004064-11).

Keywords: COPD exacerbations; COPD pharmacology; drug reactions; emphysema; idiopathic pulmonary fibrosis; lung cancer; palliative care; psychology.

Figure 1

Consolidated Standards of Reporting Trials flow diagram of patients included in the trial, follow-up and analysis. #=reasons why seven patients were consented but not randomised were because they were found or became ineligible: started pulmonary rehabilitation (1); uncontrolled diabetes mellitus (2), started taking antidepressants (1), hepatic impairment (1), decided not on optimal treatment for underlying condition (1), and one missing. * Of those who discontinued intervention, patients were willing to continue data collection in all but one in the mirtazapine group and all but four in the placebo group, all available data were analysed.

Figure 2

Mean (95% CI) breathlessness at worst and average over 24 hours during the 28 days of the study, by study arm.