Heart failure, including failure due to left ventricular dysfunction and failure with preserved ejection fraction Circulatory System
Conditions
Interventions
Randomised patients will receive either modified release morphine 10 mg capsules twice daily with docusate laxative 100mg capsules twice daily (intervention arm 1) or placebo morphine capsules twice d
Sponsors
Hull and East Yorkshire Hospitals NHS Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current exclusion criteria as of 06/07/2015: 1. Patients with New York Heart Association (NYHA) class III or IV symptoms due to heart failure as evidenced by: 1.1. Echo: left ventricular systolic dysfunction (LVSD) 40% plus left ventricular hypertrophy, left atrial dilation or abnormal diastolic function 2. N-terminal portion of B-type natriuretic peptides (NT-proBNP) =1000 pg/mL OR BNP =250 pg/mL within last 3 months 3. Optimal medical treatment of heart failure which has not changed in the previous 2 weeks 4. Adequate renal clearance within previous 2 weeks. glomerular filtration rate (GFR) =30ml/min 5. Grade 2 or more on the modified MRC dyspnoea scale 6. Aged 18 years or over Optimal medical management This will be assessed by the clinician responsible for the usual care of the patient and reviewed by the study doctor at the recruiting centre prior to study entry. Sub-optimal treatment will be addressed before study entry. Treatment (including dose of diuretic) must be stable for the two weeks prior to randomisation. Optimal treatment for patients with left ventricular dysfunction is defined as: 1. Reached target dose (or be on maximally tolerated dose, or be intolerant) of an inhibitor of the renin-angiotensin system shown to improve prognosis AND 2. Reached target dose (or be on maximally tolerated dose, or be intolerant) of a beta adrenoceptor antagonist shown to improve prognosis AND 3. Reached target dose (or be on maximally tolerated dose, or be intolerant) of an aldosterone antagonist Optimal treatment for patients with normal left ventricular function will be as assessed by their usual clinician. Previous exclusion criteria: 1. Patients with New York Heart Association (NYHA) class III or IV symptoms due to heart failure as evidenced by: 1.1. Echo: left ventricular systolic dysfunction (LVSD) 40% plus left ventricular hypertrophy, left atrial dilation or abnormal diastolic function within last 3 months 2. N-terminal portion of B-type natriuretic peptides (NT-proBNP) =1000 pg/mL OR BNP =250 pg/mL within last 3 months 3. Optimal medical treatment of heart failure which has not changed in the previous 2 weeks 4. Adequate renal clearance within previous 2 weeks. glomerular filtration rate (GFR) =30ml/min 5. Grade 2 or more on the modified MRC dyspnoea scale 6. Aged 18 years or over Optimal medical management This will be assessed by the clinician responsible for the usual care of the patient and reviewed by the study doctor at the recruiting centre prior to study entry. Sub-optimal treatment will be addressed before study entry. Treatment (including dose of diuretic) must be stable for the two weeks prior to randomisation. Optimal treatment is defined as: 1. Reached target dose (or be on
Exclusion criteria
Exclusion criteria: Patients who: 1. Are unable to provide informed consent 2. Are unable to complete baseline study questionnaires even with the assistance of the study nurse 3. Have co-existing malignant disease only if this would affect the study in the investigators? opinion 4. Have used morphine-based medications regularly (that is, most days) within the last month above the study dose. 5. Have known true morphine allergies as assessed by a clinician. 6. Have known central hypoventilation syndrome 7. Have been involved in another medicinal trial (CTIMP) within the past four weeks 8. Are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Patient-rated average intensity of breathlessness in the past 24 hours using a 0 - 10 numerical rating scale (NRS), where 0 = no breathlessness and 10 = worst imaginable breathlessness, at 4 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Further assessment of breathlessness using 0 - 10 NRS (average/past 24 hours; distress and unpleasantness) and global impression of change (GIC); 2. Assessment of related symptoms using 0-10 NRS (pain) and quality of sleep (Epworth Sleepiness Scale); sleepiness using the Karolinska Sleepiness Scale (KSS) 3. Assessment of functional status (6 minute walk; activPAL™ monitor); and cognitive function (Montreal Cognitive Assessment [MoCA]) 4. Quality of life (the Kansas City Cardiomyopathy Questionnaire - short form); 5. Health economic assessment (EQ5D; EQVAS; service utilisation); 6. Toxicity 7. NT-proBNP 8. Dose of diuretic(s) taken by participants 9. Dose of 'as required' immediate release opioid given for breathlessness taken by participants | — |
Countries
United Kingdom
Outcome results
None listed