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)

What is it about?

Breathlessness in advanced illness affects 75 million people worldwide. This includes people with lung disease, heart disease, cancers and many other illnesses. When the person’s illness can no longer be cured, breathlessness can become difficult to treat. Such ‘refractory’ breathlessness is very distressing and frightening, limits life quality and often leads to emergency hospital admission. 

There is no licenced medicinal treatment. We had identified a potential candidate treatment. This is an existing medicine, an antidepressant. Some case studies have found that it might be effective, even when people are not depressed. There is theoretical evidence too, as the medicine affects the breathing pathways in the brain. Before we tested the medicine in a full randomised trial we needed to test whether we could do such a trial and whether the medicine would be used. We did this in a feasibility trial called BETTER-B feasibility. 

The BETTER-B feasibility trial successfully recruited 64 patients with breathlessness. They received either mirtazapine (the antidepressant) or a dummy drug (placebo) from three hospitals over 12 months. We found it was possible to recruit to this kind of trial where patients have severe breathing difficulties and where participants do not know which treatment they are receiving. We had good data quality, participants were able to complete quality of life questionnaires to tell us how they are feeling, rarely missing information. Participants remained in the study. To achieve this, we had well trained research nurses who interviewed people, often at home. 

The data allowed us to calculate how many people we would need in a full trial. In-depth interviews with patients and families taught us how to conduct trials of this kind. We also found that the treatment was safe and that patients did not have unacceptable side effects.

We have used this information to apply for funding to continue this important research in an international large randomised trial to find out whether mirtazapine can improve patients’ breathlessness compared to a placebo. We are also sharing our findings in workshops and publications to help others to do these types of studies.


Featured Image