Refractory breathlessness in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), including chronic fibrotic lung disease following SARS-CoV-2 infection Respiratory Chronic obstructive pulmonary disease (COPD) Interstitial lung disease (ILD)
Conditions
Interventions
Current interventions as of 15/04/2020:
Participants with refractory breathlessness and COPD/ILD will be randomised on a 1:1 basis to receive either oral Mirtazapine (starting dose 15 mg per day) or
HADS anxiety and depression subscale scores
receipt of opioids and recruiting site.
Participants will be eligible for dose escalation to 30 mg per day at Day 14 (or two tablets of placebo) and to 45 mg per day at Day 28 (or three tablets of p
Sponsors
King's College London
University College Dublin
Eligibility
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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 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 depres
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 15/04/2020: 1. Worst breathlessness over the last 24 hours as assessed by NRS (0=no breathlessness to 10=worst possible breathlessness) at days 7, 14, 28 and 180 post start of treatment 2. Average breathlessness over the last 24 hours assessed by NRS (0=no breathlessness to 10=worst possible breathlessness) at days 7, 14, 28, 56 and 180 post start of treatment 3. Number and duration of episodes of breathlessness over the last 24 hours 4. Physical and emotional aspects of breathlessness (Dyspnoea, fatigue, emotional function, mastery) as assessed by the Chronic Respiratory Questionnaire (CRQ) at days 14, 28, 56 and 180 post start of treatment 5. Physical symptoms as assessed by the Integrated Palliative care Outcome Scale (IPOS) at days 14, 28, 56 and 180 post start of treatment 6. Quality of Life (QoL) as assessed by the EQ-5D-5L and associated VAS at days 14, 28, 56, 180 post start of treatment and Australia-modified Karnofsky Performance Scale (AKPS) at days 14, 28, 56 and 180 post start of treatment 7. Anxiety and depression as assessed by the Hospital Anxiety and Depression Scale (HADS) at days 28, 56, and 180 post start of treatment 8. Perceived self-efficacy as measured by the Generalized Self-Efficacy Scale (GSES) at day 56 post start of treatment 9. The consumption of opioids as measured by opioid medication usage at days 7, 14, 28, 56 and 180 post start of treatment 10. Healthcare services received, including out of hours care, number of emergency hospital attendances and admissions within 28 and 56 days post start of treatment and in the 3 month period prior to day 180 post start of treatment as measured by the Client Services Receipt Inventory (CSRI) 11. Safety as assessed by the occurrence of: 11.1. SAEs, SARs and SUSARs coded according to mild, moderate, or severe as reported at days 7, 14, 28 and 56 post start of treatment 11.2. Deaths by day 56 and day 180 post start of treatment 12. Toxicity as as | — |
Countries
England, Germany, Ireland, Italy, Poland, United Kingdom
Contacts
Public ContactAdejoke Oluyase
Outcome results
None listed