E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diastolic heart failure and diabetes mellitus type II |
diastolische Herzinsuffizienz und Diabetes Typ II |
insuffisance cardiaque diastolique et d’un diabète de type II |
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E.1.1.1 | Medical condition in easily understood language |
Diastolic heart failure and diabetes mellitus type II |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 |
The primary objective of this trial is to determine whether torasemide is superior to furosemide in reducing one marker (PIP) of cardiac fibrosis in subjects with diastolic heart failure and diabetes type II. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this trial are to determine whether torasemide is superior to furosemide in improving exercise capacity and diastolic function, as well as quality of life, neuroendocrine activation in subjects with diastolic heart failure and diabetes type II.
The trial also investigates clinical safety aspects.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed, written informed consent
• Males or females
• Age ≥ 18 years
• Diagnosed Diastolic Heart Failure according to the ESC guidelines (1)Signs or symptoms of heart failure, 2)Normal or mildly abnormal left ventricular ejection fraction (LVEF), 3)Evidence of diastolic left ventricular (LV) dysfunction)
• PIP ≥ 110 ng/ml or PIP ≥ 70 ng/ml if left atrial volume (LAV) > 29 ml/m²
• Diabetes type II
• Women of childbearing potential must test negative for pregnancy and must agree to use a highly effective contraceptive method (defined as pearl index < 1) during the trial period.
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E.4 | Principal exclusion criteria |
• Women during the lactation period, pregnant or of childbearing potential not using an effective contraceptive method
• Cardiac valve disease defined as regurgitation ≥grade 2
• Chronic dialysis
• Significant liver disease
• Malignant tumor
• Metabolic bone disease, autoimmune diseases or hyperthyroidism
• Prior documented intolerance to torasemide, furosemide, or sulfonylureas
• Known contraindications for torasemide or furosemide, especially hypovolemia, hypokalemia (<3,6 mmol/l), hyponatremia (< 135 mmol/l)
• Significant disorder of micturition
• Treatment with loop diuretics (e.g. torasemide, furosemide) at the time of baseline visit and throughout entire course of the trial. Patients with loop diuretics will undergo a washout of at least 5 (±2) days weeks after inclusion contact
• Treatment with mineralocorticoid receptor antagonists
• Changes in concomitant medication within the washout period
• Any patient characteristic that may interfere with compliance with the trial protocol, such as dementia, substance abuse, history of non-compliance with prescribed medications or medical appointments
• Concomitant participation in other clinical trials (Participation in another clinical trial within the last 30 days before enrollment)
• Missing willingness of the patient regarding storage and transfer of pseudonymized health data
• Patient is institutionalized because of legal or regulatory order (according to AMG § 40(1)
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in serum concentration of serum carboxy-terminal peptide of procollagen type I (PIP) at 9 months compared to baseline |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at 9 months compared to baseline |
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E.5.2 | Secondary end point(s) |
• Change in exercise capacity (peak VO2 on spiroergometry, 6-minutes walking distance) at 9 months
• Change in echocardiographic parameters of diastolic function
• (E/A, E/E´, EDT, IVRT, S/D, AR, Vp, PVARdur, Adur, Tei-Index, LV mass, LA-area) at 9 months
• Change in heart failure status (NYHA, signs and symptoms) at 9 months
• Change in neuroendocrine activation (natriuretic peptides) at 9 months
• Change in quality of life at 9 months
• Clinical tolerability of trial medication will be assesses at all visits.
• Change in laboratory parameter (CRP) at 9 months
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at 9 months compared to baseline
tolerability: at all visits |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 37 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |