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
Conditions
Interventions
Product Name: desametasone
Product Code: [desametasone]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DESAMETASONE FOSFATO
Current Sponsor code: desametasone
Other descriptive name:
Sponsors
AZIENDA SOCIO SANITARIA TERRITORIALE DEGLI SPEDALI CIVILI DI BRESCIA
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: • Dyspnea due to non-cardiac causes. • Systolic blood pressure 180 mmHg at time of screening and randomization. • Current hospitalization for acute heart failure (AHF) primarily caused by pulmonary embolism, cerebrovascular event, or acute myocardial infarction. • Current hospitalization for AHF not caused primarily by volume overload. • Temperature >38.0 °C, sepsis, septic shock, or evidence of active infection (either bacterial, fungal or viral) requiring new oral or intravenous anti-microbial treatment (either antibacterial, antifungal or antiviral therapy). • History of chronic infections, latent infections, chronic inflammatory or immunosuppressive disorders, chronic immunosuppressive therapy, ongoing chemotherapy or immunotherapy, or chronic anti-microbial therapy (either prophylactic or suppressive). • Current treatment with intravenous corticosteroids or chronic oral corticosteroid therapy for any other condition and of any duration in the past 6 months prior to randomization. • Documented active or history of hypocortisolism or hypercortisolism caused by primary/secondary adrenal gland disorders, pituitary disorders, iatrogenic conditions, or genetic forms. • Decompensated diabetes mellitus. • Acute coronary syndrome / myocardial infarction, stroke, transient ischemic attack, or intracranial bleeding in the past 90 days prior to randomization. • Any of the following major interventions performed in the past 30 days prior to randomization or planned during the current admission: major cardiac surgery, percutaneous coronary intervention, transcatheter aortic valve replacement, or percutaneous mitral valve repair; implantation of a cardiac resynchronization therapy device; implantation of a mechanical circulatory support (MCS) device; carotid artery disease revascularization; or any other surgical procedure that is considered “major” according to investigator judgement. • Heart transplant recipient, or listed for heart transplant with expectation to receive transplant during the study period, or currently using or planned for implantation of left ventricular assist device or intra-aortic balloon pump or any other MCS device, or planned inotropic support in an outpatient setting, or planned for palliative care for HF. • Hemodynamically significant (severe) uncorrected primary cardiac valvular disease planned for intervention during the study period. Secondary mitral regurgitation or tricuspid regurgitation due to dilated cardiomyopathy is not excluded unless planned for surgical or percutaneous intervention during the study period. • AHF caused by peripartum cardiomyopathy or Tako-tsubo syndrome diagnosed within the past 6 months, active myocarditis, or other acute structural heart disease. • Cardiomyopathy due to infiltrative diseases, accumulation diseases, hypertrophic obstructive cardiomyopathy, complex congenital heart diseases, or known pericardial constriction. • Invasive mechanical ventilation at time of screening (endotracheal intubation). • Symptomatic ventricular tachycardia (VT) in patients without an implantable cardioverter defibrillator in the past 90 days prior to randomization. • Symptomatic bradycardia with a documented heart rate 120 beats per minute at electrocardiogram performed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of corticosteroid therapy administered for 7 days, when added to standard therapy, in diuretic-resistant patients with AHF;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;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).;Timepoint(s) of evaluation of this end point: day 8 or to discharge | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Italy
Contacts
Public ContactProgettazione Ricerca
Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia
Outcome results
None listed