Refractory breathlessness in patients with a chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) Respiratory Chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD)
Conditions
Interventions
Participants will be randomised via minimisation in a 1:1 ratio to receive either oral mirtazapine or placebo medication for 56 days. Minimisation factors used will be: disease (COPD, ILD)
receipt of opioids and recruiting site.
Participants will be treated with 15 mg/day of oral mirtazapine or placebo equivalent with two assessments for dose escalation (at days 14 and 28 of treatment).
Sponsors
University of Technology Sydney
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients: 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 the section 9.3.3 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 Carers: 10. Identified by an included participant as the person closest to them 11. Aged =18 years 12. Able to complete questionnaires and assessments 13. Able to provide written informed consent
Exclusion criteria
Exclusion criteria: Patients: 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. 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. 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. Known renal impairment in the opinion of the identifying clinician (e.g. creatinine >132micromol/L and eGFR <30mL/min/1.73m2 x) 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 Carers: There are no specific exclusion criteria for caregivers.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Self-reported worst breathlessness over the last 24 hours at day 56 post start of treatment as assessed by numerical rating scale (NRS, 0=no breathlessness to 10=worst possible breathlessness) | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 assessed by adverse reactions (ARs) coded according to mild, moderate o | — |
Countries
Australia, New Zealand
Contacts
Public ContactBelinda Fazekas
Outcome results
None listed