E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- acute decompensated heart failure |
|
E.1.1.1 | Medical condition in easily understood language |
- symptoms like shortness of breath, leg edema
- elevated serum levels of biomarkers
- confirmed heart failure by X-ray, echocardiography |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054112 |
E.1.2 | Term | Hospitalisation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011906 |
E.1.2 | Term | Death |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022519 |
E.1.2 | Term | Intensive care |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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 aim of our study is to determine the safety and efficacy of an early goal-directed preload and afterload decrement with a target systolic blood pressure of 90-110 mm Hg by aggressive vasodilatation versus standard medical care in a non-ICU setting in patients with acute heart failure. |
|
E.2.2 | Secondary objectives of the trial |
Predefined subgroup analyses will be performed in patients < or > 75 years of age, men and women, systolic (LVEF < 45%) heart failure and heart failure with preserved LVEF, systolic blood pressure at presentation < or > 140 mm Hg, coronary artery disease present or not, BNP levels < or > 1000 pg/ml and isolated or concurrent right heart failure. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- patients with acute heart failure
- age > 18 years
- signed informed consent
- negative pregnancy test (only in female patients ≤ 60 years)
|
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E.4 | Principal exclusion criteria |
- cardiopulmonary resuscitation < 7 days
- cardiogenic shock, ST-elevation myocardial infarction, or other clinical conditions that require immediate ICU admission or urgent PTCA
- systolic blood pressure lower than 100 mm Hg at presentation
- primary rhythmogenic cause of acute decompensation (ventricular tachycardia, reentry tachycardia, atrial fibrillation or atrial flutter with a ventricular rate exceeding 140 beats per minute)
- NSTEMI as primary diagnosis
- severe aortic stenosis
- adult congenital heart disease as primary cause of acute heart failure
- hypertrophic obstructive cardiomyopathy
- chronic kidney disease with creatinine levels > 250 µmol/l
- bilateral renal artery stenosis
- severe sepsis or other causes of high output failure |
|
E.5 End points |
E.5.1 | Primary end point(s) |
-death or HF-re-hospitalization at 180 days |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- 90 days, 180 days and 360 days after enrollment |
|
E.5.2 | Secondary end point(s) |
- all-cause mortality at 180 d
- HF re-hospitalisation at 180 d
- re-hospitalisation from all causes at 180 d
- need for ICU admission during initial hospitalisation
- B-type natriuretic peptide (BNP) and creatinine level at 48 h and at discharge
- changes in circumferences of both legs and central venous pressure during hospitalisation
- change in patient-assessed dyspnea at 48 h and prior to discharge
- blood pressure course over the first 6 days
- time to disappearance of a third heart sound (if present initially)
- time to discharge
- in-hospital days for heart failure at 180 and 360 days
- total treatment cost at 180 and 360 days
- functional status at 180 and 360 days
- quality of life at 180 and 360 days
- fractures due to falls within 180 and 360 days
- death or heart failure rehospitalisation at 360 days |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 90 days, 180 days and 360 days after enrollment |
|
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
standard therapy of acute decompensated heart failure following the ESC guidelines |
|
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Bulgaria |
Germany |
Latvia |
Serbia |
Spain |
Switzerland |
United Kingdom |
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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
|
The end of the trial is defined on n = 770 plus a 360 day follow up period (Last visit last subject) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
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 |