Condition category
Respiratory
Date applied
31/05/2016
Date assigned
13/06/2016
Last edited
13/06/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Breathlessness is a common symptom affecting 50-70% of people with cancer and over 90% of people with non-cancer lung disease. In some cases, even when the underlying causes are treated, the breathlessness itself continues (refractory breathlessness). This can be very distressing, causing fear and panic; reduced quality of life, including social life; and can result in emergency hospital admissions. At the moment, there is no standard treatment for refractory breathlessness. This study is looking at a commonly used antidepressant drug called mirtazapine, which is used to treat depression and anxiety. This drug affects a brain chemical called serotonin, which is active when people are breathless. Reports involving small numbers of patients suggest that mirtazapine may be an effective treatment for breathlessness, possibly because it also reduces feelings of panic. The aim of this study is to find out whether conducting a small trial looking at the effectiveness of mirtazapine in the treatment of refractory breathlessness is feasible and whether enough patients can be recruited to take part.

Who can participate?
Adult patients with cancer or non-cancer lung disease experiencing refractory breathlessness.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group take 15mg tablets of mirtazapine every day for 28 days. Half way through the study (day 14) participants have their breathlessness assessed on a numbered scale to find out if it has improved. If there is no improvement and the drug is not causing any side effects, then the dose is doubled for the remaining 14 days of the study. Those in the second group take a placebo (dummy pill) every day for 28 days. Participants are then followed up for seven days following completion of the study to find out if their breathlessness has improved. After 12 months, the number or participants recruited to the study are recorded in order to find out if enough patients could be recruited.

What are the possible benefits and risks of participating?
Not provided at time of registration.

Where is the study run from?
1. Kings College Hospital (UK)
2. Castle Hill Hospital (UK)
3. Hull Royal Infirmary (UK)
4. Nottingham City Hospital Campus (UK)
5. Queens Medical Centre Campus (UK)

When is the study starting and how long is it expected to run for?
November 2015 to January 2018

Who is funding the study?
Marie Curie Cancer Care (UK)

Who is the main contact?
Dr Heather Cook
better-b@leeds.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Heather Cook

ORCID ID

Contact details

Clinical Trials Research Unit
University of Leeds
Leeds
LS2 9JT
United Kingdom
+44 113 3438942
better-b@leeds.ac.uk

Additional identifiers

EudraCT number

2015-004064-11

ClinicalTrials.gov number

Protocol/serial number

30471

Study information

Scientific title

BETter TreatmEnts for Refractory Breathlessness: A feasibility study of the use of mirtazapine for refractory breathlessness

Acronym

BETTER-B (Feasibility)

Study hypothesis

The aim of this study is to determine the feasibility of conducting a large-scale randomised, double-blind, placebo-controlled study of mirtazapine for refractory breathlessness.

Ethics approval

London - Central Research Ethics Committee, 29/01/2016, ref: 16/LO/0091

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Respiratory disorders, Primary sub-specialty: Respiratory disorders; UKCRC code/ Disease: Respiratory/ Other diseases of the respiratory system

Intervention

Participants will be randomised via minimisation on a 1:1 ratio to receive either oral mirtazapine (15mg/day) or placebo medication for 28 days. At day 14 of treatment breathlessness intensity (“at worst” over the previous 24 hours) will be assessed using the numerical rating scale (NRS). If there is no improvement in NRS (i.e. NRS does not increase by 1 point or more compared to baseline NRS) and the drug has been well tolerated, the daily dose of treatment will be doubled. Participants will be followed up for 7 days after completing trial treatment

Intervention type

Drug

Phase

Not Applicable

Drug names

Mirtazapine

Primary outcome measures

Recruitment rate is measured by the number of patients recruited across three hospitals over 12 months.

Secondary outcome measures

Not provided at time of registration

Overall trial start date

01/11/2015

Overall trial end date

31/01/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male or female aged ≥ 18 years old
2. Modified MRC dyspnoea scale grade 3 or 4
3. Diagnosis of either:
3.1. Cancer
3.2. Chronic obstructive pulmonary disease (COPD)
3.3. Interstitial lung disease (ILD)
3.4. Chronic heart failure (New York Heart Association class III or IV)
4. On optimal treatment of the underlying condition in the opinion of the identifying clinician
5. Management of the underlying condition unchanged for the previous 1 week
6. Reversible causes of breathlessness optimally treated in the opinion of the identifying clinician
7. Expected prognosis of ≥2 months
8. If female and of child-bearing potential, must agree to use adequate contraception
9. Able to complete questionnaires and trial assessments
10. Able to provide written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 60; UK Sample Size: 60

Participant exclusion criteria

1. Existing antidepressant use
2. Known contraindication to mirtazapine
3. Hypersensitivity to the active substance or to any of the components of the mirtazapine or placebo (e.g. lactose intolerance)
4. Australia modified Karnofsky Performance Scale ≤40
5. Pregnant or breast-feeding women
6. Patients with acute cardiac events within 3 months of randomisation (myocardial infarction, unstable angina pectoris, or significant cardiac conduction disturbance)
7. Patients with known hepatic impairment
8. Patients with known renal impairment
9. Patients with uncontrolled blood pressure
10. Patients with uncontrolled diabetes mellitus
11. Patients with uncontrolled seizures, epilepsy or organic brain syndrome
12. Patients with severe depression or suicidal thoughts
13. Patients with a history of psychotic illness (schizophrenia, bipolar disorder, mania or hypomania, or other psychotic disturbances)

Recruitment start date

01/08/2016

Recruitment end date

31/07/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Kings College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Castle Hill Hospital
Castle Road
Cottingham
HU16 5JQ
United Kingdom

Trial participating centre

Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

Nottingham City Hospital Campus
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Queens Medical Centre Campus
Lister Road
Nottingham
NG7 2RT
United Kingdom

Sponsor information

Organisation

Kings College Hospital NHS Foundation Trust

Sponsor details

161 Denmark Hill
London
SE5 8EF
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Marie Curie Cancer Care

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Results of the study are intended to be reported in a peer reviewed scientific journal once data collection and data analysis is completed.

Intention to publish date

31/01/2019

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes