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

NCT04618601 | Unknown Phase 4

• 1 other identifier: 15606
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure Acute; Heart Failure; With Decompensation

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Daily urine output

  Urine output in liters per 24 hours will be tracked from enrollment to day 5.

  5 days

Secondary Outcomes (6)

• Total urine output

  5 days

• Total weight change

  5 days

• Daily weight change

  5 days

• Natriuresis on days 1, 3 and 5

  5 days

• Changes in natriuresis between days 1, 3 and 5

  5 days

Study Arms (2)

High-dose spironolactone

ACTIVE COMPARATOR

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

Drug: Spironolactone

Standard of care

NO INTERVENTION

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

Interventions

Spironolactone 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.

Also known as: Aldactone

High-dose spironolactone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laikο General Hospital, Athens: lead

Study Sites (1)

Laiko General Hospital

Athens, Attica, 11527, Greece

Location

Related 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.

  PMID: 29971596 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Cardio-Renal Syndrome

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• John Barbetseas, MD

  Laikon General Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiology Fellow

Study Record Dates

• First Submitted: November 1, 2020
• First Posted: November 6, 2020
• Study Start: October 20, 2020
• Primary Completion: December 20, 2021
• Study Completion: March 1, 2022
• Last Updated: November 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)