Efficacy and Safety of corticoSTEROids Added to Standard Therapy in Patients With Acute Heart Failure (STERO-AHF)

NCT05809011 | Unknown Phase 2 DMC

• 2 other identifiers: NP56762022-003206-69
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

STERO-AHF is a pilot, prospective, multicenter, randomized, open-label, controlled study aimed to evaluate the diuretic efficacy and early clinical benefit of corticosteroid therapy administered for 7 days, in addition to standard therapy, in patients hospitalized for acute heart failure (AHF) and with evidence of insufficient diuretic response. Eligible patients will be randomized 1:1 to receive either standard-of-care alone (control group) or standard-of-care plus corticosteroid therapy (experimental group) for up to 7 days. Patients will be followed to 30 days.

Conditions

Acute Heart Failure

Keywords

Acute heart failure; Diuretic resistance; Inflammation; Corticosteroids; Diuretic response

Outcome Measures

Primary Outcomes (2)

• Diuretic response, defined as absolute body weight change per 40 mg total dose of intravenous furosemide or equivalent

  Absolute change in body weight (in kg) per 40 mg total dose of intravenous furosemide or equivalent over the preceding days of the study (equivalent intravenous doses: bumetanide 1 mg, torsemide 20 mg).

  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)

• 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)

  All-cause death is defined as the occurrence of death from any cause. Worsening HF is defined as worsening signs and/or symptoms of HF that require an intensification of intravenous therapy for HF or mechanical ventilatory, renal or circulatory support. Such treatment can include the introduction or up-titration of intravenous diuretics, intravenous nitrates, intravenous inotropes, intravenous vasoactive agents or any other intravenous therapy for HF, or institution of mechanical support such as mechanical ventilation, ultrafiltration, hemodialysis, intra-aortic balloon pumping or ventricular assist device, etc. The absolute change in patient-reported dyspnea is quantified according to the VAS scoring system, a 0-100 mm scale that rates the absolute degree of dyspnea. Patients rate their level of dyspnea on a linguistically-validated scale that rates from 0 to 100, with 0 representing the worst conceivable dyspnea and 100 representing the best imaginable ability to breathe.

  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 Outcomes (8)

• Hierarchical composite outcome of all-cause death, total number of heart failure (HF) events, and absolute change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (KCCQ-TSS)

  At day 30

• Absolute change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (KCCQ-TSS)

  From baseline to day 30

• Improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (KCCQ-TSS) of ≥5 points

  At day 30

• Absolute change in log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP) level

  From baseline to day 30

• Daily urinary output per daily loop diuretic dose

  At day 4 or at the occurrence of death (in patients dying before day 4)

Other Outcomes (13)

• Change in patient-reported dyspnea as quantified by the area under the curve (AUC) of daily visual analogue scale (VAS) scores (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)

• Absolute change in patient-reported dyspnea visual analogue scale (VAS) score

  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)

• Worsening heart failure (HF)

  At day 8

Study Arms (2)

Corticosteroid therapy plus standard-of-care

EXPERIMENTAL

Patients randomized to this arm will receive a single-bolus intravenous injection of dexamethasone 20 mg at day 1 (as soon as possible after randomization), followed by oral prednisone 1 mg/kg daily (maximum 60 mg daily) from day 2 to day 7 after randomization. Patients randomized to this arm will also receive standard-of-care therapy for acute heart failure.

Drug: Dexamethasone; Drug: Prednisone

Standard-of-care

NO INTERVENTION

Patients randomized to this arm will receive standard-of-care therapy for acute heart failure.

Interventions

Dexamethasone DRUG

After enrollment and randomization, the intervention (experimental arm) will be the administration of corticosteroid therapy, added to standard therapy for acute heart failure. Corticosteroid therapy will be administered as a single-bolus intravenous injection of dexamethasone 20 mg (day 1, as soon as possible after randomization), followed by oral prednisone 1 mg/kg daily (maximum 60 mg daily) from day 2 to day 7 after randomization, administered at about 8.00 AM.

Corticosteroid therapy plus standard-of-care

Prednisone DRUG

After enrollment and randomization, the intervention (experimental arm) will be the administration of corticosteroid therapy, added to standard therapy for acute heart failure. Corticosteroid therapy will be administered as a single-bolus intravenous injection of dexamethasone 20 mg (day 1, as soon as possible after randomization), followed by oral prednisone 1 mg/kg daily (maximum 60 mg daily) from day 2 to day 7 after randomization, administered at about 8.00 AM.

Corticosteroid therapy plus standard-of-care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Full age of consent at screening (at least ≥18 years old according to local legislation).
• Able to provide written informed consent or a legally authorized representative is able to provide written informed consent.
• Hospitalized for AHF, either de novo or decompensated chronic HF, regardless of LVEF.
• Treatment with a minimum single dose of 40 mg of intravenous furosemide or equivalent intravenous loop diuretic dose (defined as 20 mg of torsemide or 1 mg of bumetanide) at any time between presentation and the end of screening.
• Insufficient diuretic response assessed at 2-6 hours after the first intravenous loop diuretic dose administration, according to the latest 2021 ESC guidelines on the management of acute and chronic HF, defined as either urinary sodium \<70 mEq/L at a single spot urinary sodium analysis performed at 2 hours or an average urine output \<150 mL/h in the first 6 hours after first intravenous diuretic administration. In case of early insufficient diuretic response and persistence of congestion, the dose of intravenous loop diuretic will have to be doubled and the patient may be enrolled.
• New York Heart Association functional class II, III or IV at screening.
• Elevated NT-proBNP ≥1400 pg/mL or BNP ≥350 pg/mL according to the local laboratory for patients without atrial fibrillation, or NT-proBNP ≥2200 pg/mL or BNP ≥550 pg/mL for patients with atrial fibrillation at the time of admission and/or in the 72 hours prior to hospital admission.
• Elevated CRP ≥10 mg/L according to the local laboratory, measured during the current hospitalization.
• Eligible for randomization within the first 24 hours from presentation.

You may not qualify if:

• Dyspnea due to non-cardiac causes.
• Systolic blood pressure \<90 mmHg or \>180 mmHg at time of screening and randomization.
• Current hospitalization for AHF primarily caused by pulmonary embolism, cerebrovascular event, or acute myocardial infarction.
• Current hospitalization for AHF not caused primarily by volume overload; for example, triggered by significant arrhythmia (e.g., sustained ventricular tachycardia \[VT\], or atrial fibrillation/flutter with sustained ventricular response \>120 beats per minute, or bradycardia with sustained ventricular rate \<45 beats per minute), infection/sepsis, severe anemia, uncorrected thyroid disease, or acute exacerbation of chronic obstructive pulmonary disease.
• Temperature \>38.0 °C (oral or equivalent), 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 (e.g., adrenal insufficiency, Cushing disease or Cushing syndrome, prior chronic long-standing corticosteroid therapy).
• Decompensated diabetes mellitus, defined as the presence of diabetic ketoacidosis, hyperglycemic hyperosmolar state, or glycemia \> 250 mg/dL as measured at the latest local laboratory exams performed during hospitalization.
• 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 (e.g., coronary artery bypass graft or valve replacement), percutaneous coronary intervention, transcatheter aortic valve replacement, or percutaneous mitral valve repair (e.g., transcatheter edge-to-edge mitral valve repair); implantation of a cardiac resynchronization therapy device; implantation of a mechanical circulatory support (MCS) device; carotid artery disease revascularization (percutaneous intervention or surgery); 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 (according to investigator judgement), 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 (e.g., acute mitral cord rupture).
• Cardiomyopathy due to infiltrative diseases (e.g., amyloidosis), accumulation diseases (e.g., haemochromatosis, Fabry disease), hypertrophic obstructive cardiomyopathy, complex congenital heart diseases, or known pericardial constriction.

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

ASST Spedali Civili di Brescia

Brescia, 25123, Italy

RECRUITING

MeSH Terms

Conditions

Inflammation

Interventions

Dexamethasone; Prednisone

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Pregnadienediols

Central Study Contacts

Matteo Pagnesi, MD

CONTACT

+39 3272834112; m.pagnesi@gmail.com

Marco Metra, MD

CONTACT

+39 0303995572; marco.metra@unibs.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 19, 2023
• First Posted: April 12, 2023
• Study Start: April 24, 2023
• Primary Completion: November 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)