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)

Irene J Higginson; Andrew Wilcock; Miriam J Johnson; Sabrina Bajwah; Natasha Lovell; Deokhee Yi; Simon P Hart; Vincent Crosby; Heather Poad; David Currow; Emma Best; Sarah Brown; BETTER-B Feasibility Trial Group

doi:10.1136/thoraxjnl-2019-213879

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)

Thorax. 2020 Feb;75(2):176-179. doi: 10.1136/thoraxjnl-2019-213879. Epub 2020 Jan 8.

Authors

Collaborators

Affiliations

¹ Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation, Kings College London and King's College Hospital NHS Foundation Trust, London, UK irene.higginson@kcl.ac.uk.
² Department of Clinical Oncology, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.
³ Wolfson Palliative Care Research Centre, Hull York Medical School, The University of Hull, Hull, UK.
⁴ Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation, Kings College London and King's College Hospital NHS Foundation Trust, London, UK.
⁵ Respiratory Research Group, Hull York Medical School, University of Hull, Castle Hill Hospital, University of Hull, Hull, Kingston upon Hull, UK.
⁶ Palliative Care, Nottingham University Hospitals NHS Trust, Nottingham, UK.
⁷ Clinical Trials Research Unit (CTRU), University of Leeds, Leeds, West Yorkshire, UK.
⁸ Faculty of Heath, University of Technology Sydney, Sydney, New South Wales, Australia.

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.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Adult
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Dyspnea / diagnosis
Dyspnea / drug therapy*
Europe
Feasibility Studies
Female
Follow-Up Studies
Humans
Lung Diseases, Interstitial / diagnosis
Lung Diseases, Interstitial / drug therapy*
Lung Diseases, Interstitial / mortality
Male
Maximum Tolerated Dose
Middle Aged
Mirtazapine / therapeutic use*
Patient Selection*
Pulmonary Disease, Chronic Obstructive / diagnosis
Pulmonary Disease, Chronic Obstructive / drug therapy*
Pulmonary Disease, Chronic Obstructive / mortality
Severity of Illness Index
Treatment Outcome

Substances

Mirtazapine

Grants and funding

MCCC-RP-15-A18859/MCCC_/Marie Curie/United Kingdom