Efficacy and Safety of corticoSTEROids Added to Standard Therapy in Patients With Acute Heart Failure (STERO-AHF)
- Registration Number
- NCT05809011
- 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.
- Detailed Description
STERO-AHF is a pilot, prospective, multicenter, randomized, open-label, controlled clinical trial designed to evaluate the efficacy, safety and tolerability of corticosteroid therapy administered for 7 days, when added to standard therapy, in patients with acute heart failure (AHF) and evidence of insufficient diuretic response. After assessing eligibility for the study (screening period), 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.
Study candidates will be adult patients who fulfill the following key inclusion criteria: 1) hospitalized with a primary diagnosis of AHF, either de novo or decompensated chronic heart failure (HF), regardless of left ventricular ejection fraction; 2) insufficient diuretic response at 2-6 hours after the first intravenous loop diuretic dose administration; 3) persistent dyspnea at rest or after mild exertion and clinical signs of fluid overload; 4) elevated C-reactive protein ≥ 10 mg/L at hospital admission. Patients with systolic blood pressure \<90 mmHg at time of screening and with severe renal impairment defined as estimated glomerular filtration rate \<20 mL/min/1.73m2 or need of chronic dialysis or temporary renal replacement therapy will be excluded from the study.
After enrollment and randomization, patients assigned to corticosteroid therapy will receive it as a single-bolus intravenous injection of dexamethasone 20 mg (day 1), followed by oral prednisone 1 mg/kg daily (maximum 60 mg daily) from day 2 to day 7 after randomization. All enrolled subjects will receive standard-of-care therapy for AHF, including tailored diuretic therapy according to current management strategies for patients with insufficient diuretic response after intravenous loop diuretic dose administration.
The study aim is to evaluate the diuretic efficacy and early clinical benefit of corticosteroid therapy administered for 7 days, when added to standard therapy, in diuretic-resistant patients with AHF. All randomized patients will be assessed daily while hospitalized up 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), and then will be followed-up at a scheduled visit at 30 days.
The primary endpoints will be assessed at day 8 after randomization or at discharge (in patients discharged earlier than day 8) or at the occurrence of death (in patients dying before day 8). For the safety evaluation, all adverse events will be collected from signing of the informed consent form through day 30. The duration of enrollment will be of \~24 months. The primary completion of the study is the date when the last enrolled patient is assessed for the collection of the primary endpoint. The end of the study is the date when the last enrolled patient has completed the last follow-up visit.
A total of 9 Italian high-volume, tertiary-care centers will be involved in the study. Based on sample size calculations, the trial is targeted to enroll 120 patients with AHF to provide sufficient statistical power to detect a significant difference in diuretic response (primary endpoint).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Corticosteroid therapy plus standard-of-care Prednisone 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. Corticosteroid therapy plus standard-of-care Dexamethasone 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.
- Primary Outcome Measures
Name Time Method Diuretic response, defined as absolute body weight change per 40 mg total dose of intravenous furosemide or equivalent 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 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).
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) 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.
- Secondary Outcome Measures
Name Time Method Absolute change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (KCCQ-TSS) From baseline to day 30 KCCQ-TSS is a well-established tool to evaluate health status and quality-of-life in patients with HF. KCCQ is a 23-item, self-administered health status measure for the quantification of HF-related health status. The domains quantified by the KCCQ include physical limitation, symptoms, self-efficacy, quality-of-life, and social limitation. The TSS quantifies symptom frequency and severity and ranges from 0 to 100, with higher score indicating better function.
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 HF event is defined as a hospitalization, an Emergency Department visit, an urgent care visit or an outpatient visit with all the following criteria met: hospitalization or visit due to a primary diagnosis of HF or worsening of HF; at least one symptom of HF; at least two physical examination findings of HF or at least one physical examination finding plus one positive diagnostic test of HF; intensification of therapy for HF.
KCCQ-TSS is a well-established tool to evaluate health status and quality-of-life in patients with HF. KCCQ is a 23-item, self-administered health status measure for the quantification of HF-related health status. The domains quantified by the KCCQ include physical limitation, symptoms, self-efficacy, quality-of-life, and social limitation. The TSS quantifies symptom frequency and severity and ranges from 0 to 100, with higher score indicating better function.Absolute change in log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP) level From baseline to day 30 NT-proBNP is measured in pg/mL
Improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (KCCQ-TSS) of ≥5 points At day 30 KCCQ-TSS is a well-established tool to evaluate health status and quality-of-life in patients with HF. KCCQ is a 23-item, self-administered health status measure for the quantification of HF-related health status. The domains quantified by the KCCQ include physical limitation, symptoms, self-efficacy, quality-of-life, and social limitation. The TSS quantifies symptom frequency and severity and ranges from 0 to 100, with higher score indicating better function.
Daily urinary output per daily loop diuretic dose 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) Daily urine output is measured in mL or L.
Daily loop diuretic dose is defined as the daily dose (in mg) of oral or intravenous loop diuretics converted to furosemide equivalents: 1 mg bumetanide = 20 mg torsemide = 80 mg furosemide for oral diuretics; 1 mg bumetanide = 20 mg torsemide = 40 mg furosemide for intravenous diuretics. The oral loop diuretic dose is considered to be half the intravenous loop diuretic dose.Absolute change in serum creatinine 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) Serum creatinine is measured in mg/dL
Absolute change in estimated glomerular filtration rate (eGFR), calculated 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) eGFR is measured in mL/min/1.73 m2
Trial Locations
- Locations (1)
ASST Spedali Civili di Brescia
🇮🇹Brescia, Italy