A multicenter, randomized, open-label, controlled study to evaluate the efficacy and safety of corticoSTEROids added to standard therapy in patients with Acute Heart Failure (STERO-AHF)

INTERVENTION: Product Name: desametasone Product Code: [desametasone] Pharmaceutical Form: Solution for injection INN or Proposed INN: DESAMETASONE FOSFATO Current Sponsor code: desametasone Other descriptive name: desametasone Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Product Name: terapia standard Product Code: [terapia standard] Pharmaceutical Form: Tablet INN or Proposed INN: terapia cardiaca standard Current Sponsor code: terapia standard Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Product Name: prednisone Product Code: [prednisone] Pharmaceutical Form: Tablet INN or Proposed INN: PREDNISONE Current Sponsor code: prednisone Concentration unit: mg milligram(s) Concentration type: up to Concentration number: 25‐ CONDITION: patients with Acute Heart Failure ; MedDRA version: 20.0 Level: PT Classification code 10007556 Term: Cardiac failure acute System Organ Class: 10007541 ‐ Cardiac disorders ; MedDRA version: 20.0 Level: PT Classification code 10007556 Term: Cardiac failure acute System Organ Class: 10007541 ‐ Cardiac disorders ; MedDRA version: 20.0 Level: LLT Classification code 10066332 Term: Acute cardiac insufficiency System Organ Class: 10007541 ‐ Cardiac disorders Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] PRIMARY OUTCOME: Main Objective: To evaluate the efficacy of corticosteroid therapy administered for 7 days, when added to standard therapy, in diuretic‐resistant patients with AHF Primary end point(s): Diuretic response, defined as absolute body weight change from baseline to day 8 or to discharge (in patients discharged earlier than day 8) or to the occurrence of death (in patients dying before day 8) per 40 mg total dose of intravenous furosemide or equivalent over the preceding days of the study.; • Early clinical benefit, defined as a hierarchical composite outcome including all‐cause death, worsening heart failure (HF), and the absolute change in patient‐reported dyspnea as quantified by the visual analogue scale (VAS) score (0‐100 mm scale) from baseline to day 8 or to discharge (in patients discharged earlier than day 8) or to the occurrence of death (in patients dying before day 8). Secondary Objective: To evaluate the superiority of corticosteroid therapy, given for 7 days in addition to standard therapy, compared to standard therapy alone, compared to other clinical endpoints, health conditions, symptoms, vital and functional signs, laboratory tests and other medical therapies over the period a total follow‐up period of 30 days Timepoint(s) of evaluation of this end point: day 8 or to discharge SECONDARY OUTCOME: Secondary end point(s): Hierarchical composite outcome of all‐cause death, total number of HF events, and absolute change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (KCCQ‐TSS) at 30 days after randomization.; Absolute change in the KCCQ‐TSS from baseline to day 30.; ; • Absolute change in log‐transformed NT‐proBNP level from baseline to day 30.; Improvement in KCCQ‐TSS of =5 points at 30 days after randomization.; Daily urinary output per daily loop diuretic dose assessed at day 4 or at the occurrence of death (in patients dying before day 4).; Daily urinary output per daily loop diuretic dose assessed at day 8 or at discharge (in patients discharged earlier than day 8) or at the occurrence of death (in patients dying before day 8).; Absolute change in log‐transformed NT‐proBNP level from baseline to day 30.; Absolute change in serum creatinine and estimated glomerular filtration rate (eGFR) according to the CKD‐EPI equation from baseline to day 8 or to discharge (in patients discharged earlier than day 8) or to the occurrence of death (in patients dying before day 8). Timepoint(s) of evaluation of this end point: 30 days after randomization.; day 30; 30 days after randomization.; day 4 day 8; day 30; day 8 or to discharge INCLUSION CRITERIA: > =18 2. Able to provide written informed consent or a legally authorized representative is able to provide written informed consent. I 3. Hospitalized for AHF, regardless of LVEF. Patients must have persistent dyspnea at rest or with mild exertion and at least one of the following signs of fluid overload : pulmonary congestion on chest X‐ray or lung ultrasound; rales on chest auscultation; clinically relevant peripheral or pre‐sacral edema (e.g., =1+ on a scale from 0 to 3+); or elevated jugular venous pressure. 4. Treatment with a minimum single dose of 60 mg of intravenous furosemide or equivalent intravenous loop diuretic dose (defined as 30 mg of torsemide or 1.5 mg of bumetanide) 5. Early insufficient diuretic response in patients receiving an initial loop diuretic dose >125 mg of intravenous furosemide or equivalent OR persistent insufficient diuretic response inpatients receiving an initial loop diuretic dose <125 mg of intravenous furosemi