Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure (DANAUS-AHF)

Laikο General Hospital, Athens

Status and phase: Unknown; Phase 4

Conditions: Heart Failure; With Decompensation; Heart Failure Acute

Treatments: Drug: Spironolactone

Study type: Interventional

Funder types: Other

Identifiers

NCT04618601

15606

Details and patient eligibility

About

This is a prospective, single-center, open-label and randomized trial for evaluation of the effect of a 5-day administration of high doses of spironolactone (≥100mg daily) on diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with acute decompensated heart failure (ADHF). Mineralocorticoid receptor antagonists (MRAs) are recommended as standard of care (SOC) in management of heart failure (HF) patients. However, recommended doses of MRAs (up to 50mg daily) have any impact on signs and symptoms of volume overload. Therefore, the proposed study will aim to show the impact of high doses of spironolactone to improve diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with ADHF.

Full description

Congestion represents a hallmark feature of ADHF, which is present in more than 90% of patients hospitalized for this diagnosis. Intravenous loop diuretics are the mainstay of treatment. Nonetheless, nearly half of the patients who are hospitalized for AdHF continue to have residual symptoms and sign of congestion at time of discharge. Various pharmacological and non-pharmacological interventions have been proposed over the past years as potential means for relieving congestion in hospitalized ADHF patients. However, their efficacy has not been shown.

Given that hyperaldosteronism is a key feature in HF, the hypothesis that administration of high doses of spironolactone can potentiate the natriuretic effects of loop diuretics and relieve congestion in the setting of ADHF has been raised.

According to the most recent guidelines spironolactone can be considered in combination with loop diuretic in patients with resistant edema or insufficient symptomatic response. However, spironolactone at a dose of 100 mg daily has failed to increase diuresis in patients with ADHF.

The present study will assess the effect of high per os doses of spironolactone (≥100mg) on top of SOC treatment compared with SOC treatment alone on diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with ADHF.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of acute heart failure within the past 8 hours
• Two of the following: 1. edema, 2. ascites, 3. jugular vein distention, 4. pulmonary congestion
• NT-proBNP >1,000 pg/ml or >3,000 pg/ml (in the presence of atrial fibrillation)
• Per os mean daily loop diuretic dose equivalent to 80 mg of furosemide for at least 1 month prior to presentation and at least one of the following: 1. serum urea/serum creatinine > 50 at presentation, 2. serum creatinine increased >0.3 mg/dl compared with previous value (within the last year), 3. serum creatinine > 1.8 mg/dl.

Exclusion criteria

• pregnancy or breast feeding
• current acute coronary syndrome
• significant valvular disease
• pulmonary embolism
• allergy or intolerance to spironolactone
• current mechanical circulatory support
• primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy
• mean arterial pressure <65mmHg or systolic arterial pressure <90 mmHg at presentation
• anticipated use of inotropes or vasodilators (other than renal doses of dopamine, i.e. <2.5 μg/kg/min)
• anticipated need of ultrafiltration
• exposure to nephrotoxic agents within 3 days of presentation
• serum potassium> 5 mmol/L
• per os receipt of spironolactone or eplerenone in a dose > 50 mg daily prior to presentation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

High-dose spironolactone

Active Comparator group

Description:

Participants in this arm will receive high doses of per os spironolactone, defined as doses ≥100 mg daily, on top of standard of care treatment for acute heart failure

Treatment:

Drug: Spironolactone

Standard of care

No Intervention group

Description:

Participants in this arm will standard of care treatment for acute heart failure, which may include per os spironolactone at a maximum dose of 50 mg daily