E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced heart failure with reduced ejection fraction (less than or equal to 40%) with significant breathlessness that limits what they are able to do. MRC Dyspnoea Scale ≥2. |
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E.1.1.1 | Medical condition in easily understood language |
Severely weak heart pump and breathlessness |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
We want to determine whether inhaled furosemide relieves breathlessness in patients with heart failure. This is to test the benefit of adding inhaled furosemide to existing treatment in chronic heart failure.
The principle research objective: Determine the effect of inhaled furosemide on breathlessness in patients with chronic heart failure
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E.2.2 | Secondary objectives of the trial |
To determine the effect of inhaled furosemide on different aspects (physical and emotional) of breathlessness in patients with advanced chronic heart failure.
To determine the effect of inhaled furosemide on breathlessness with exercise.
To the effect of inhaled furosemide on the blood biomarkers of heart failure.
To assess the changes in health-related quality of life for patients with heart failure with inhaled furosemide.
To assess anxiety, depression and fatigue in patients with heart failure and the correlate to their breathlessness ratings.
To assess the affect of inhaled furosemide on activity levels.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1)Patient is willing and able to give informed consent for participation in the trial. 2)Male or Female, aged 18 years or above. (There is no upper age limit although the investigator will ensure they have the capacity to understand, consent and have the ability to perform the studies required.) 3)Diagnosed with heart failure more than 3 months ago. 4)Diagnosed with heart failure with a documented reduced ejection fraction <40% 5)Significant breathlessness that limits what they are able to do. MRC Dyspnoea Scale ≥2. 6)In the Investigator's opinion, is able and willing to comply with all trial requirements. 7)Female participants of child bearing potential must be willing to ensure that they use effective contraception during the period they are taking the IMP/placebo and for 48hours after Visit 5. 8) Prescribed regular furosemide or bumetanide tablets for at least 1 month
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E.4 | Principal exclusion criteria |
1)Those unable to consent for themselves 2)History of allergic reaction (hypersensitive) to furosemide and/or any of the other ingredients of furosemide or amiloride, sulfonamides or sulphonamide derivatives, such as sulfadiazine or co-trimoxazole 3)Unplanned heart failure related hospital admission within the last month (unstable heart failure). 4)Patients diagnosed with heart failure within the last 3 months (unstable heart failure) 5)Individuals who are dehydrated or have significant symptomatic postural hypotension 6)Significant renal impairment (eGFR <15) or anuric 7)Potassium <3.0 or >5.9 or Sodium <130 or >150 over the preceding month prior the screening visit. 8)Significant hepatic impairment/cirrhosis (Child-Pugh class C) 9)Addison's disease 10)Digitalis intoxication 11)Porphyria 12)Individuals who are immunocompromised 13)Patient with life expectancy <6 months 14)Co-existent history of significant chronic obstructive pulmonary disease or asthma or interstitial lung disease or nasal polyps 15)Patients on inhaled B2 agonist therapy 16)Any other significant disease or disorder which, in the opinion of the Investigator, may either put the patients at risk because of participation in the trial, or may influence the result of the trial, or the patient’s ability to participate in the trial. 17)Have participated in another research trial involving investigational product in the past 4 weeks. 18)Female patients who are pregnant, lactating or planning pregnancy over the course of trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
Visual analogue scale (VAS) ratings of 'air hunger (AH)' during experimentally induced breathlessness to determine the effect of inhaled furosemide on breathlessness in patients with chronic heart failure.
The VAS is a 10cm line with one end marked as 'no breathlessness at all' and the other end marked as 'worst possible breathlessness.' The participant marks across the line to indicate the level of breathlessness experienced during a test that is designed to make participants feel breathless (air hunger). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
40 patients attending the hospital on 5 occasions. Visits 2-5 will be the timepoints of evaluation for the primary and secondary endpoints. |
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E.5.2 | Secondary end point(s) |
- Total score on Dyspnoea 12 questionnaire. - Peak workload, heart rate, oxygen consumption at peak and at anaerobic threshold achieved during cardiopulmonary exercise testing (CPET)or the 6-minute walk test if participant cannot perform CPET. Severity of breathlessness during these exercise tests using the VAS and/or Borg. - Blood biomarkers of heart failure (BNP and NT-proBNP). - Minnesota Living with Heart Failure Questionnaire (MLHFQ). - Trait and State Anxiety Questionnaire, Center for Epidemiological Studies depression scale, Fatigue severity score. - Activity levels from wearable watch.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
40 patients attending the hospital on 5 occasions. Visits 2-5 will be the timepoints of evaluation for the primary and secondary endpoints. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 1 |