Corticosteroids added to standard therapy for acute heart failure

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)

This study is testing if adding corticosteroids to regular treatment helps people in the hospital with acute heart failure who aren't responding well to diuretics.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Brescia)
• Trial ID: NCT05809011 on ClinicalTrials.gov

What this trial studies

The STERO-AHF trial is a multicenter, randomized, open-label study that evaluates the efficacy and safety of corticosteroid therapy in patients hospitalized for acute heart failure who show insufficient response to diuretics. Participants will be randomly assigned to receive either standard care alone or standard care plus corticosteroids for a duration of 7 days. The study aims to assess the diuretic efficacy and early clinical benefits of this combined treatment approach. Patients will be monitored for 30 days following treatment to evaluate outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults hospitalized with acute heart failure and insufficient diuretic response.

Not a fit: Patients with severe renal impairment or low systolic blood pressure may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve diuretic response and clinical outcomes for patients with acute heart failure.

How similar studies have performed: While corticosteroids have been explored in various contexts, this specific approach in acute heart failure is novel and has not been extensively tested.

Eligibility criteria

Inclusion criteria:

1. Full age of consent at screening (at least ≥18 years old according to local legislation).
2. Able to provide written informed consent or a legally authorized representative is able to provide written informed consent.
3. Hospitalized for AHF, either de novo or decompensated chronic HF, regardless of LVEF.
4. 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.
5. 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.
6. New York Heart Association functional class II, III or IV at screening.
7. 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.
8. Elevated CRP ≥10 mg/L according to the local laboratory, measured during the current hospitalization.
9. Eligible for randomization within the first 24 hours from presentation.

Exclusion criteria:

1. Dyspnea due to non-cardiac causes.
2. Systolic blood pressure \<90 mmHg or \>180 mmHg at time of screening and randomization.
3. Current hospitalization for AHF primarily caused by pulmonary embolism, cerebrovascular event, or acute myocardial infarction.
4. 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.
5. 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).
6. 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).
7. 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.
8. 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).
9. 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.
10. Acute coronary syndrome / myocardial infarction, stroke, transient ischemic attack, or intracranial bleeding in the past 90 days prior to randomization.
11. 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.
12. 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.
13. 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.
14. 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).
15. 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.
16. Invasive mechanical ventilation at time of screening (endotracheal intubation). Continuous or intermittent non-invasive mechanical ventilation is allowed.
17. Symptomatic VT in patients without an implantable cardioverter defibrillator in the past 90 days prior to randomization.
18. Symptomatic bradycardia with a documented heart rate \<50 beats per minute at electrocardiogram performed before randomization or evidence of advanced atrio-ventricular block (third-degree or second-degree type 2) without a pacemaker.
19. Atrial fibrillation/flutter with a documented, persistent resting heart rate \>120 beats per minute at electrocardiogram performed before randomization.
20. Severe impairment of renal function, defined as eGFR \<20 mL/min/1.73m2 (according to the CKD-EPI equation) as measured at the latest local laboratory exams performed during hospitalization (between presentation and the end of screening), or requiring chronic dialysis or temporary renal replacement therapy.
21. Acute contrast-induced nephropathy.
22. Severe anemia, defined as hemoglobin \<8 g/dL as measured at the latest local laboratory exams performed during hospitalization.
23. Any major solid organ transplant recipient or planned organ transplant during the study period.
24. Known history of glaucoma.
25. Prior gastrointestinal surgery or gastrointestinal disorder that could interfere with the absorption of the study drug (according to investigator judgement).
26. Documented active or suspected malignancy or history of malignancy of any organ system within 1 year prior to screening, except appropriately treated localized basal cell carcinoma of the skin.
27. Presence of any disease other than HF with life expectancy less than 6 months.
28. Decision for palliative care in HF (informed patient decision to adhere to limited HF treatments only).
29. Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial, or less than five half-lives of the study drug (whichever is longer) in case of drug trial. Patients participating in a purely observational study will not be excluded.
30. Known allergy or hypersensitivity to any corticosteroid or any excipient of the study drug product.
31. Chronic alcohol or drug abuse or any condition that makes the patient unreliable or unlikely to complete the trial (according to investigator judgement).
32. Inability to follow instructions or comply with follow-up procedures.
33. Pregnant or nursing (lactating) women. Women of child-bearing potential must have a negative urine or serum pregnancy test prior to enrollment.
34. Any other medical condition that may put the patient at risk or influence study results according to the investigator judgement, or that the investigator deems unsuitable for the study.
35. Inability to comply with all study requirements, due to major comorbidities that might compromise the patient's ability to understand and/or comply with the protocol instructions or follow-up procedures.

Where this trial is running

Brescia

• ASST Spedali Civili di Brescia — Brescia, Italy (RECRUITING)

Study contacts

• Study coordinator: Matteo Pagnesi, MD

Conditions: Acute Heart Failure, Acute heart failure, Diuretic resistance, Inflammation, Corticosteroids, Diuretic response