Refractory breathlessness in patients diagnosed with cancer, chronic heart failure, or lung disease (chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD)). MedDRA version: 18.1 Level: LLT Classification code 10006345 Term: Breathlessness System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Mirtazapine
Product Name: Mirtazapine
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: mirtazapine
CAS Number: 85650-
Sponsors
King's College London
King's College Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged = 18 years old 2. Modified MRC dyspnoea scale grade 3 or 4 3. Diagnosed with: • Cancer, or • Chronic obstructive pulmonary disease (COPD), or • Interstitial lung disease (ILD), or • Chronic heart failure (New York Heart Association (NYHA) class III or IV) 4. On optimal treatment of the underlying condition in the opinion of the identifying clinician (see section 9.3.3 of protocol for guidance) 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 must be (as documented in the notes) a) postmenopausal (no menses for 12 months without an alternative medical cause), or b) surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or c) using acceptable contraception ii (which must be continued for 7 days after the last dose of IMP) 9. Able to complete questionnaires and trial assessments 10. Able to provide written informed consent ii Acceptable contraception is defined as one of the following: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; practising true abstinence (when this is in line with the preferred and usual lifestyle of the subject). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Existing antidepressant use, use of linezolid, or St John’s wort 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(vi) 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) vi for women of childbearing potential (those not post-menopausal or surgically sterile) must be confirmed by a pregnancy test within 7 days prior to randomisation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 1. Is a large-scale randomised, double-blind, placebo-controlled study of mirtazapine for refractory breathlessness feasible in terms of: a)Recruitment in different settings: outpatient, community services and inpatient settings? b) Acceptability of randomisation to patients? c) Ability to deliver placebo-control and maintain the double-blind? d) Ability to assess outcome measures and minimise missing data in a future large-scale trial? e) Patient eligibility to increase the dose of mirtazapine further at 28 days? f) Compliance with treatment? 2. In order to further inform the sample size calculation for the future large-scale trial, what is the expected activity of mirtazapine? 3. What is the toxicity profile of mirtazapine in patients with breathlessness? 4. What is the potential impact on quality of life (QoL) and symptom management of mirtazapine for patients with breathlessness? ;Main Objective: Is a large scale, randomised, double blind, placebo-controlled study of mirtazapine for refractory breathlessness feasible in terms of recruitment?; Primary end point(s): The primary endpoint is the number of patients recruited into the trial across 3 trial sites over a 12-month period. This will be evaluated at the end of the trial. ;Timepoint(s) of evaluation of this end point: After 12 months recruitment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: All secondary endpoints will be evaluated when all participants have been followed up for safety i.e. 7 days after last treatment dose.; Secondary end point(s): Other outcome measures of feasibility will be assessed to determine whether the design of the future large-scale trial may need to be adapted to improve recruitment or reduce attrition. Physical activity and toxicity outcomes will be used to inform the design of the future trial, however they will not be used to inform the decision as to whether or not to proceed to a future large-scale trial. These are: • Number of patients screened for eligibility and reasons for non-eligibility • Proportion of eligible patients randomised and reasons for non-randomisation • Proportion of participants for which blinding is maintained • Proportion of research assessors for which blinding is maintained • Proportion of participants remaining on study for 28 days • Proportion of, and reasons for, participants with missing data for trial outcomes • Proportion of participants who would be eligible for dose escalation at 28 days • Treatment compliance over the period Feasibility outcome measures relating to recruitment will be assessed by the use of screening logs completed at each site. Blinding will be assessed using the Bang Blinding index. Missing data and study compliance will be assessed based on completed and received CRFs, summarised for each trial outcome measure. Eligibility for dose escalation will be assessed based on breathlessness intensity at day 28 and tolerability of treatment. 3) Safety and Toxicity •Adverse events reported on days 7, 14, 21 and 28. •Safety will be reported based on the occurrence of SAEs, SARs and | — |
Countries
United Kingdom
Contacts
Public ContactVictoria Hiley
Clinical Trials Research Unit (CTRU)
Outcome results
None listed