E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute (decompensated) heart failure |
acuut hartfalen |
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E.1.1.1 | Medical condition in easily understood language |
Situation of decreased pumping capacity of the heart resulting in symptoms and signs of fluid retention, dyspnea and acute admission to hospital |
Situatie van verminderde pompfunctie van het hart met als consequentie vocht vasthouden, kortademigheid en acute opname in het ziekenhuis |
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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 | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10019280 |
E.1.2 | Term | Heart failures |
E.1.2 | System Organ Class | 100000004849 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10019283 |
E.1.2 | Term | Heart failure signs and symptoms |
E.1.2 | System Organ Class | 100000004908 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000803 |
E.1.2 | Term | Acute heart failure |
E.1.2 | System Organ Class | 100000011689 |
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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 evaluate whether empagliflozin 10mg/day will relieve dyspnea, improves diuretic response, decreases length of initial hospital stay and NT-proBNP compared to placebo during hospital admission for acute decompensated heart failure. |
Het primary doel van deze studie is het onderzoeken of Empagliflozine 10 mg/dag dyspnoe verbetert, diuretische response verbetert, ziekenhuisopname verkort en NTproBNP levels verlaagd vergeleken met placebo tijdens opname voor acuut hartfalen
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this trial are to evaluate the effects of empagliflozin on change in dyspnea, renal function, and NT-proBNP and on 30-day death and/or heart failure hospital. |
Secundaire doelen zijn het onderzoeken van het effect van Empagliflozine op verandering in dyspnoe, nierfunctie, NTproBNP en 30 dagen mortaliteit en hartfalen heropnames |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female >18 years of age; 2. Hospitalized for AHF; AHF is defined as including all of the followings measured at any time between presentation (including the emergency department) and the end of screening: a. Dyspnea at rest or with minimal exertion b. Signs of congestion, such as edema, rales, and/or congestion on chest radiograph c. BNP ≥350 pg/mL or NT-proBNP ≥1,400 pg/mL (for patients with AF: BNP≥500 pg/mL or NT-proBNP ≥2,000 pg/mL) d. Treated with loop diuretics at screening 3. Able to be randomized within 24 hours from presentation to the hospital 4. Able and willing to provide freely given written informed consent 5. eGFR (CKD-EPI) ≥30 ml/min/1.73m2 between presentation and randomization |
1. Mannen of Vrouwen > 18 jaar. 2. Opname voor Acuut Hartfalen gedefinieerd als: - Dyspnoe in rust of bij minimale inspanning - Tekenen van congestie - BNP ≥350 pg/mL of NT-proBNP ≥1,400 pg/mL (bij atriumfibrilleren: BNP≥500 pg/mL or NT-proBNP ≥2,000 pg/mL) - Behandeling met lisdiuretica op screening 3) Randomisatie binnen 24 uur mogelijk 4) Informed consent 5) eGFR > 30 ml/min/1.73 m2 |
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E.4 | Principal exclusion criteria |
1. Dyspnea primarily due to non-cardiac causes 2. Cardiogenic shock 3. Acute coronary syndrome within 30 days prior to randomization 4. Planned or recent percutaneous or surgical coronary intervention within 30 days prior to randomization 3. Signs of keto-acidosis and/or hyperosmolar hyperglaecemic syndrome (pH>7.30 and glucose >15 mmol/L and HCO3>18 mmol/L) 4. Pregnant or nursing (lactating) women 5. Current participation in any interventional study 6. Inability to follow instructions or comply with follow-up procedures 7. Any other medical conditions that may put the patient at risk or influence study results in the investigator’s opinion, or that the investigator deems unsuitable for the study. |
1) Dyspnoe door niet cardiale oorzaken 2) Cardiogene shock 3) Acute coronaire syndromen binnen 30 dagen voor randomisatie 4) Geplande coronaire interventie 5) Tekenen van Keto-Acidose en/of hyperosomolair hyperglycemisch syndroom 6) Zwangeren of vrouwen die borstvoeding geven 7) Deelname aan een interventie studie 8) Onmogelijkheid om instructies op te volgen 9) Overige medische condities die het risico voor de patient vergroot of de studie resultaten kan beinvloeden, of patienten die andersinds niet geschikt zijn voor de studie |
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E.5 End points |
E.5.1 | Primary end point(s) |
a) Dyspnea relief, assessed by VAS at baseline to day 4 (or discharge if earlier); b) Diuretic response (defined as Δ weight kg/[(total i.v. dose)/40mg]+[(total oral dose)/80mg)] furosemide (or equivalent loop diuretic dose) up to day 4 c) Length of initial hospital stay; d) Change in NT-proBNP from baseline to day 4 (or discharge if earlier) |
- Verandering in Dyspnoe score (VAS) in de eerste 4 dagen van opname - Verandering in Diuretische Response in de eerste 4 dagen van opname - Verandering in NTproBNP levels in de eerste 4 dagen van opname - Verandering in opnameduur |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 days and inhospital stay (variable) |
4 dagen en tijd in ziekenhuis |
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E.5.2 | Secondary end point(s) |
Death and/or heart failure re-admission at day 30 Change in plasma values of renal function, including creatinine, eGFR, cystatin C, BUN, renal biomarkers and hemoglobin, hematocrit, albumin from baseline to day 4 (or discharge if earlier) or day 30 Change in urinary renal biomarkers to day 4 o day 30 Adverse events to 60 days |
- Dood en/of hartfalen rehospitalisatie binnen 30 dagen - adverse events tot 60 dagen na opname - Veranderingen in biomarkers van nierfunctie, hemoconcentratie en urine markers of 4 en 30 dagen |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
day 4 and day 30 |
4 en 30 dagen |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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
| 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 | 5 |
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 | 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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LVLS (telephone call) |
Laatste telefonische visite van laatste subject |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |