E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 |
Determination of the course of BNP (B-type natriuretic peptide) over 4 months of constant therapy and its correlation to other objective HF parameters (e.g. LVEF, NYHA-class, quality of life) in order to generate further efficacy data for the angiotensin II type I receptor blocker Candesartan Cilexetil in the treatment of heart failure when administered in an "added" regimen to standard HF therapy with at least ACE inhibitors.
|
|
E.2.2 | Secondary objectives of the trial |
In addition the following secondary efficacy variables will be analysed: • Mean change from baseline (V1) to V6 for LVEF, NYHA-class, SF-36-score and NT-proBNP • Mean change from V4 to V6 for NYHA-class, BNP and NT-proBNP • Correlations of BNP with LVEF, NYHA classification, SF-36 score and NT-proBNP • Subgroup evaluation regarding beta-blocker therapy (yes/no) and NYHA classification (II / III) • Subgroup evaluation in terms of the different possible dosages of study medication during the 16 weeks of constant therapy (i.e. for 8, 16 or 32 mg Candesartan)
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Male or female patients of at least 18 years of age - Heart failure with systolic dysfunction and LVEF ≤ 40% since at least 4 weeks without any expected deterioration in the next 4 months according to clinical experience - NYHA classification of II or III in a stable condition since at least 3 months - Existing standard HF therapy with an ACE inhibitor alone or together with further preparations in a constant regimen since at least 1 month, in case of beta-blockers since at least 3 months - BNP values at baseline of more than 200 pg/ml - No previous therapy with angiotensin-receptor blockers (ARBs) during the last 4 weeks prior to the study - A woman of childbearing potential must have a negative pregnancy test before study start, routinely use oral or injectable contraceptives or intrauterine devices during the study and plan not to become pregnant during the study - A woman of non-childbearing potential could be included if postmenopausal for at least one year or surgically sterilised or hysterectomised at least three months before study start - Available signed written informed consent
|
|
E.4 | Principal exclusion criteria |
- Primary diastolic dysfunction (e.g. amyloidosis or cardiomyopathy) - Impaired renal function (serum creatinine > 2.2 mg/dl or > 194 µmol/l) - Known bilateral renal artery stenosis (RAS) or interventional treatment for RAS in the last year - State after kidney transplantation - Serum potassium higher than 5.5 mmol/l - Known disposition to symptomatic hypotension or sSBP < 95 mmHg at baseline - Myocardial infarction, open heart surgery or cerebral event (stroke/TIA) in the last 3 months - Hemodynamically relevant stenosis of the aortic and/or mitral valve - Relevant liver diseases (cholestasis or ALAT/ASAT > 2xULN or Gamma GT > 3xULN) - History of primary hyperaldosteronism, of cancer in the last 5 years (exception: non metastasizing skin cancer) or of another wasting disease with life expectancy of < 2 years - Known hypersensitivity to Candesartan Cilexetil - Concomitant long-term therapy with NSAIDs or Cox-2-inhibitors - Use of other ARBs throughout the entire study period - Any history of life-threatening diseases - Female patients who are pregnant or breast feeding
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Course of BNP (mean change from baseline (V1) to V6) |
|
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 | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |