BETTER-B: Better Treatments for Refractory Breathlessness
- Conditions
- Refractory breathlessness in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), including chronic fibrotic lung disease following SARS-CoV-2 infectionRespiratoryChronic obstructive pulmonary disease (COPD) Interstitial lung disease (ILD)
- Registration Number
- ISRCTN10487976
- Lead Sponsor
- King's College London
- Brief Summary
2024 Results article in https://pubmed.ncbi.nlm.nih.gov/39265600/ (added 16/09/2024)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- Not specified
- Target Recruitment
- 324
Current inclusion criteria as of 29/09/2020:
1. Aged= 18 years old
2. Diagnosed with:
2.1. Chronic obstructive pulmonary disease (COPD), and/or
2.2. Interstitial lung disease (ILD), including chronic fibrotic lung disease following SARS-CoV-2 infection
3. Breathlessness severity: Modified MRC breathlessness scale of:
3.1. Grade 3 (I stop for breath after walking about 100 yards or after a few minutes on level ground) or
3.2. Grade 4 (I am too breathless to leave the house or I am breathless when dressing or undressing)
4. On optimal treatment of the underlying condition in the opinion of the identifying clinician (see section 0 of protocol for guidance)
5. Management of the underlying condition unchanged for the previous 2 weeks
6. Reversible causes of breathlessness optimally treated in the opinion of the identifying clinician
7. If female, must be (as documented in patient notes):
7.1. Postmenopausal (no menses for 12 months without an alternative medical cause), or
7.2. Surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or
7.3. Using acceptable contraception (which must be continued for 7 days after the last dose of IMP )
8. Able to complete questionnaires and trial assessments
9. Able to provide written informed consent
_____
Previous inclusion criteria:
1. Aged =18 years old
2. Diagnosed with:
2.1. Chronic obstructive pulmonary disease (COPD), and/or
2.2. Interstitial lung disease (ILD)
3. Breathlessness severity: Modified MRC breathlessness scale of:
3.1. Grade 3 (I stop for breath after walking about 100 yards or after a few minutes on level ground) or
3.2. Grade 4 (I am too breathless to leave the house or I am breathless when dressing or undressing)
4. On optimal treatment of the underlying condition in the opinion of the identifying clinician (see section 0 of protocol for guidance)
5. Management of the underlying condition unchanged for the previous 2 weeks
6. Reversible causes of breathlessness optimally treated in the opinion of the identifying clinician
7. If female, must be (as documented in patient notes):
7.1. Postmenopausal (no menses for 12 months without an alternative medical cause), or
7.2. Surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or
7.3. Using acceptable contraception (which must be continued for 7 days after the last dose of IMP )
8. Able to complete questionnaires and trial assessments
9. Able to provide written informed consent
Current exclusion criteria as of 29/09/2020:
1. Existing antidepressant use , or other serotonergic active substances (e.g. linezolid, St John’s wort)
2. Known contraindication to mirtazapine
3. Hypersensitivity to the active substance or to any of the components of mirtazapine or placebo (e.g. lactose intolerance)
4. Australia modified Karnofsky Performance Scale =40
5. Pregnant or breast-feeding women. For women of childbearing potential (those not post-menopausal or surgically sterile) this must be confirmed by a pregnancy test (urine) within 7 days prior to randomisation
6. Patients with acute cardiac events within 3 months prior to randomisation (e.g. myocardial infarction, unstable angina pectoris, or significant cardiac conduction disturbance) in the opinion of the identifying clinician
7. Patients with jaundice or known hepatic impairment in the opinion of the identifying clinician (e.g. bilirubin >25micromol/L, and AST and ALT >2 times upper limit of normal)
8. Patients with known renal impairment in the opinion of the identifying clinician (e.g. creatinine >132micromol/L and eGFR <30mL/min/1.73m2)
9. Uncontrolled blood pressure in the opinion of the identifying clinician
10. Uncontrolled diabetes mellitus in the opinion of the identifying clinician
11. Uncontrolled seizures, epilepsy or organic brain syndrome in the opinion of the identifying clinician
12. Severe depression or suicidal thoughts in the opinion of the identifying clinician
13. History of psychotic illness (schizophrenia, or other psychotic disturbances) in the opinion of the identifying clinician
14. Bipolar disorder, or a history of mania or hypomania in the opinion of the identifying clinician
15. Currently enrolled in another interventional trial
16. Patients with known congenital QT prolongation or family history for QT prolongation
17. Use of medicines that cause QT prolongation such as macrolides and typical antipsychotics (unless required in low-dose to relieve nausea, e.g. haloperidol =5mg/24h, levomepromazine =25mg/24h)
18. Patients with a known history of suicide-related events
_____
Previous exclusion criteria:
1. Existing antidepressant use , or other serotonergic active substances (e.g. linezolid, St John’s wort)
2. Known contraindication to mirtazapine
3. Hypersensitivity to the active substance or to any of the components of mirtazapine or placebo (e.g. lactose intolerance)
4. Australia modified Karnofsky Performance Scale =40
5. Pregnant or breast-feeding women. For women of childbearing potential (those not post-menopausal or surgically sterile) this must be confirmed by a pregnancy test (urine) within 7 days prior to randomisation
6. Patients with acute cardiac events within 3 months prior to randomisation (e.g. myocardial infarction, unstable angina pectoris, or significant cardiac conduction disturbance) in the opinion of the identifying clinician
7. Patients with jaundice or known hepatic impairment in the opinion of the identifying clinician (e.g. bilirubin >25micromol/L, and AST and ALT >2 time
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Self-reported worst breathlessness over the past 24 hours measured at day 56 post start of treatment using a numerical rating scale (NRS, 0=no breathlessness to 10=worst possible breathlessness)
- Secondary Outcome Measures
Name Time Method