E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic stable heart failure (NYHA II-IV, ejection fraction ≤ 40%)
Vitamin D deficiency (defined as 25 (OH) Vitamin D ≤ 30ng/ml) |
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E.1.1.1 | Medical condition in easily understood language |
Heart failure, vitamin D deficiency |
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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 study is to investigate whether vitamin D-supplementation leads to a significant reduction of NT-proBNP levels at month 6. |
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E.2.2 | Secondary objectives of the trial |
- Percentage of patients with 25(OH)D ≥ 30 ng/ml at month 6
- Serum calcium, phosphorus, 25(OH)D, 1,25(OH)D, PTH, osteocalcin, renin, aldosterone, OPG and RANKL, urinary calcium
- Frozen serum/plasma for potential other analysis (eg. TNFα, IL 6, IL 10)
- Overall mortality at 6 months
- number and duration of hospital admissions for acute heart failure
- number of infectious complications requiring antibiotics
- falls/fractures
- corrected QT time in ECG
- blood pressure
- DXA including body composition at month 0 and 6 or 12
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Chronic stable heart failure (NYHA II-IV, ejection fraction ≤ 40%)
• Non-ischemic etiology or ischemic etiology without severe advanced atherosclerosis (e.g. peripheral arterial disease stage IV)
• ≥ 45 years
• 25 (OH) Vitamin D ≤ 30ng/ml
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E.4 | Principal exclusion criteria |
• hypercalcemia (total serum calcium > 2.65 mmol/l OR ionized calcium > 1.35 mmol/l)
• nephrocalcinosis, nephro-/urolithiasis (≤1 year)
• known granulomatous diseases (active tuberculosis, sarcoidosis)
• allergy to cholecalciferol or placebo (oleum arachidis)
• intake of magnesium, thiazide diuretics or cardiac glycosides
• osteoporosis requiring standard therapy
• pregnancy
|
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change of NT-proBNP levels |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Percentage of patients with 25(OH)D ≥ 30 ng/ml at month 6
- Serum calcium, phosphorus, 25(OH)D, 1,25(OH)D , PTH, osteocalcin, renin, aldosterone, OPG and RANKL, urinary calcium
- Frozen serum/plasma for potential other analysis (eg. TNFα, IL 6, IL 10)
- Overall mortality at 6 months
- number and duration of hospital admissions for acute heart failure
- number of infectious complications requiring antibiotics
- falls/fractures
- corrected QT time in ECG, blood pressure
- DXA including body composition at month 0 and 12
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
months 0,6 and 12 (see specification above for each secondary end point) |
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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 | No |
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) | 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
|
Total study duration for each patient will be 6 months with a follow-up visit at 12 months.
Total study duration will be approximately 15 months. |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |