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

Heart Failure; With Decompensation Clinical Trial

— DANAUS-AHF  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04618601
• Other study ID #: 15606
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 20, 2020
• Est. completion date: March 1, 2022

Study information

• Verified date: November 2020
• Source: Laik? General Hospital, Athens
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: March 1, 2022
• Est. primary completion date: December 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure Acute
• Heart Failure; With Decompensation

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Greece	Laiko General Hospital	Athens	Attiki

Sponsors (1)

Lead Sponsor	Collaborator
Laik? General Hospital, Athens

Country where clinical trial is conducted

Greece, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Daily urine output	Urine output in liters per 24 hours will be tracked from enrollment to day 5.	5 days
Secondary	Total urine output	Urine output in total liters from enrollment to day 5 will be measured.	5 days
Secondary	Total weight change	Patient weight in kilos will be tracked from enrollment to day 5.	5 days
Secondary	Daily weight change	Patient weight in kilos will be tracked from enrollment to day 5.	5 days
Secondary	Natriuresis on days 1, 3 and 5	Urine sodium will be measured on days 1, 3 and 5	5 days
Secondary	Changes in natriuresis between days 1, 3 and 5	Urine sodium will be measured on days 1, 3 and 5	5 days
Secondary	Changes in NT-proBNP between days 1 and 5	NT-proBNP will be measured on days 1, 3 and 5	5 days