E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
Evaluate the time to in-hospital Worsening of Heart Failure (WHF) requiring rescue therapy/all cause death |
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E.2.2 | Secondary objectives of the trial |
- Evaluate the time to in-hospital WHF requiring rescue therapy/all cause death/readmission for HF.
- Evaluate the percentage of patients with persistent signs or symptoms of HF/ non-improvement
- Evaluate the percentage of patients with renal deterioration.
- Evaluate the length of stay.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Explore biomarkers changes
- Better understand the beneficial effects of serelaxin
- Monitor patient's response to therapy
2. Plasma proteome analysis
Impact of serelaxin in addition to SOC vs. SOC alone on the changes in plasma proteome at day 5 vs baseline
3. Nitric Oxide Sub-study
-explore and elucidate the effect
on the Nitric Oxide (NO) pathway of a 48 hours intravenous administration of serelaxin or the SOC at D2 (48 hours) compared to baseline (0 hours). |
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E.3 | Principal inclusion criteria |
- Male or female ≥ 18 years of age with body weight ≥ 40 Kg and ≤ 160 Kg
- Systolic blood pressure ≥125 mmHg at the beginning of the screening period (after ICF signature) and at the end of the screening period (prior to randomization)
- Admitted for AHF: Persistent dyspnea at rest or with minimal exertion, Pulmonary congestion assessed through physical examination and chest X-Ray
- Furosemide at any time between admission and the start of screening
- eGFR on admission: ≥25 and ≤75 mL/min/1.73 m2
- BNP ≥500 pg/mL or N-terminal pro b-type natriuretic peptide (NT-proBNP)≥2,000 pg/mL
Other protocol-defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
- Dyspnea (non-cardiac causes) such as acute or chronic respiratory disorders or infections (i.e., severe chronic obstructive pulmonary disease, bronchitis, pneumonia), or primary pulmonary hypertension sufficient to cause dyspnea at rest, which may interfere with the ability to interpret the primary cause of dyspnea.
- T >38.5°C
- Clinical evidence of acute coronary syndrome
- AHF due to arrhythmias, acute myocarditis or cardiomyopathy
- Known history of respiratory disorders requiring the daily use of
IV steroids (does not include inhaled or oral steroids) at least 2
months prior to randomization; need for intubation or the current
use of IV steroids for COPD
-Patients with systolic blood pressure > 180 mmHg at end of screening or persistent heart rate >130 bpm
-History of malignancy of any organ system (other than localized
basal cell carcinoma of the skin), treated or untreated, within the
past year
Other protocol-defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Time to in-hospital Worsening of heart failure (WHF) requiring rescue therapy or all cause death through Day 5 post randomization.
- Time will be computed in hours from randomization to the earlier of the events.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Trough Day 5 post randomization |
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E.5.2 | Secondary end point(s) |
- Time to in-hospital Worsening of heart failure requiring rescue therapy as defined in the primary endpoint, or all cause of death or readmission for heart failure. Time will be computed in hours from randomization to the earlier of the events.
- Percentage of patients with persistent symptoms or signs of Heart Failure / not showing an improvement versus baseline conditions (persisting need of IV therapy for HF).
- Percentage of patients with renal deterioration, defined as ≥ 0.3 mg/dL increase in serum creatinine.
- Lengh of Stay (LOS). It will be defined as hours from the index hospitalization and the discharge. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- All cause of death or readmission for heart failure and or renal failure will be evaluated through Day 14 post randomization.
- Persistent symptoms or signs of HF / no improvement will be evaluated at 6, 12, 24 and 48 hours from start of drug infusion, daily through index hospitalization and through Day 5.
- Renal deterioration will be evaluated at 24 and 48 hours from start of drug infusion, at Day 5 and at Day 14.
- Length of stay will be evaluated through Day 30 post randomization. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 |
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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 | 557 |
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 |
Austria |
Belgium |
Bulgaria |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Iceland |
Italy |
Norway |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
Slovenia |
Spain |
Sweden |
Switzerland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 4 |
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 | 5 |