Better treatments for refractory breathlessness
| ISRCTN | ISRCTN32236160 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN32236160 |
| EudraCT/CTIS number | 2015-004064-11 |
| Secondary identifying numbers | 30471 |
- Submission date
- 31/05/2016
- Registration date
- 13/06/2016
- Last edited
- 15/12/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
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
Contact information
Public
Clinical Trials Research Unit
University of Leeds
Leeds
LS2 9JT
United Kingdom
| Phone | +44 113 3438942 |
|---|---|
| better-b@leeds.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | BETter TreatmEnts for Refractory Breathlessness: A feasibility study of the use of mirtazapine for refractory breathlessness |
| Study 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(s) | London - Central Research Ethics Committee, 29/01/2016, ref: 16/LO/0091 |
| 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 by phone 7 days after the end of trial treatment to assess whether any adverse events or reactions have occurred. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Mirtazapine |
| Primary outcome measure | Recruitment rate is measured by the number of patients recruited across three hospitals over 12 months. |
| Secondary outcome measures | Feasibility: 1. Number of patients screened for eligibility and reasons for non-eligibility 2. Proportion of eligible patients randomised and reasons for non-randomisation 3. Proportion of patients for which blinding is maintained 4. Proportion of research assessors for which blinding is maintained 5. Proportion of patients remaining on study for 28 days 6. Proportion of and reasons for patients with missing data for trial outcomes 7. Proportion of patients who would be eligible for dose escalation at 28 days 8. Treatment compliance over the period Activity, symptoms and quality of life: 1. Breathlessness mastery is assessed using the Chronic Respiratory Questionnaire (CRQ) and modified Medical Research Council (mMRC) dyspnoea scale on day 14 and day 28 2. Lower extremity functioning is measured using the Short Physical Performance Battery (SPPB) on day 28 3. Coping self-belief is measured using the Generalized Self-Efficacy Scale (GSES) on day 28 4. Palliative symptoms is measured using the Integrated Palliative care Outcome Scale (IPOS) on day 14 and day 28 5. Anxiety and depression are measured using the Hospital Anxiety and Depression Scale (HADS) on day 14 and day 28 6. Quality of life is measured using the EQ-5D-5L on day 28 and Australian-modified Karnofsky Performance Scale (AKPS) on day 14 and day 28 7. Health Economics are assessed using the Client Services Receipt Inventory (CSRI) on day 28 Safety and toxicity: 1. Adverse reactions are assessed using the Common Terminology Criteria for Adverse Events (CTCAE) categorisation on days 7, 14, 21 and 28 2. Occurrence of SAEs, SARs and SUSARs 3. Opioid medication is assessed on days 7, 14, 21 and 28 |
| Overall study start date | 01/11/2015 |
| Overall study end date | 26/12/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 60; UK Sample Size: 60 |
| Total final enrolment | 64 |
| 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 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
- England
- United Kingdom
Study participating centres
London
SE5 9RS
United Kingdom
Cottingham
HU16 5JQ
United Kingdom
Hull
HU3 2JZ
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG7 2RT
United Kingdom
Sponsor information
Hospital/treatment centre
161 Denmark Hill
London
SE5 8EF
England
United Kingdom
"ROR" |
https://ror.org/01n0k5m85 |
|---|
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- Marie Curie Cancer Care
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/01/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| 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. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/02/2020 | 10/01/2020 | Yes | No |
| Results article | qualitative results | 22/02/2020 | 24/02/2020 | Yes | No |
| Protocol file | version 2.0 | 11/02/2016 | 15/12/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
15/12/2022: Protocol uploaded (not peer reviewed).
24/02/2020: Publication reference added.
10/01/2020: Publication reference and total final enrolment number added.
07/02/2019: The overall trial end date was changed from 31/01/2018 to 26/12/2018.
30/01/2017: The secondary outcome measures have been added.
