Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure

NCT ID: NCT04618601

Last Updated: 2020-11-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-20
• Study Completion Date: 2022-03-01

Brief Summary

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.

Detailed 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.

Conditions

Heart Failure Acute; Heart Failure; With Decompensation

Keywords

diuretic resistance; spironolactone; cardio-renal syndrome; diuretics; natriuresis; heart failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

High-dose spironolactone

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

Group Type: ACTIVE_COMPARATOR

Spironolactone

Intervention Type: DRUG

Patients randomized to the high-dose spironolactone group will receive oral spironolactone (≥100 mg) on top of standard of care treatment for acute heart failure immediately after randomization and in the afternoon of each subsequent day unless the serum potassium level is \>5 mmol/L. The exact dose will be determined based on a pre-specified algorithm provided.

Standard of care

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Spironolactone

Patients randomized to the high-dose spironolactone group will receive oral spironolactone (≥100 mg) on top of standard of care treatment for acute heart failure immediately after randomization and in the afternoon of each subsequent day unless the serum potassium level is \>5 mmol/L. The exact dose will be determined based on a pre-specified algorithm provided.

Intervention Type: DRUG

Other Intervention Names

Aldactone

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Laikο General Hospital, Athens

OTHER

Sponsor Role: lead

Responsible Party

Chris Kapelios

Cardiology Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John Barbetseas, MD

Role: STUDY_CHAIR

Laikon General Hospital

Locations

Laiko General Hospital

Athens, Attica, Greece

Countries

Greece

References

Kapelios CJ, Bonou M, Vogiatzi P, Tzanis G, Mantzouratou P, Lund LH, Barbetseas J. Association Between High-Dose Spironolactone and Decongestion in Patients with Acute Heart Failure: An Observational Retrospective Study. Am J Cardiovasc Drugs. 2018 Oct;18(5):415-422. doi: 10.1007/s40256-018-0290-3.

Reference Type: BACKGROUND

PMID: 29971596 (View on PubMed)

Other Identifiers

15606

Identifier Type: -

Identifier Source: org_study_id