Gender-Based Differences in Heart Failure Hospitalizations Among Patients With Heart Failure Treated With Spironolactone

Completed

• Conditions: Heart Failure; Heart Failure With Reduced Ejection Fraction; Heart Failure NYHA Class II; Heart Failure NYHA Class III; Heart Failure NYHA Class IV
• Interventions: Drug: Spironolactone

• Registration Number: NCT06641284
• Lead Sponsor: Ahmad Abdullah Salawi

Brief Summary

Aldosterone antagonists or mineralocorticoid receptor antagonists (MRAs) are used as therapeutic agents for the management of HF with reduced ejection fraction (HFrEF). Gender-related differences have been described in the regulation of the renin-angiotensin-aldosterone system (RAAS), which is at the core of the pathophysiology of HF. Regarding gender-related differences in the use of MRAs, less is known about the effects of androgens on the RAAS, even though studies have suggested that androgens may increase the RAAS pathway. There are conflicting results because many clinical trials were not specifically designed to investigate gender differences.

Detailed Description

The RALES trial investigated the effect of spironolactone on symptomatic HF patients without any difference in treatment benefits between both genders. However, only 30 % of the patients enrolled were females. Another trial investigated the gender-based differences in the treatment of HFpEF patients with spironolactone. The results showed no significant sex differences in clinical endpoints, but a substantial reduction in all-cause mortality was associated with spironolactone use in females but not in males. The utilization of HF pharmacotherapy has been controversial, given recent discoveries presented by the PARAGON-HF trial.

Study Timeline

• Study Start: 2023-10-01
• Study First Submitted: 2024-10-11
• Study First Submitted QC: 2024-10-11
• Primary Completion: 2024-10-15
• Study Completion: 2024-10-15
• Study First Posted: 2024-10-15
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-19
• Last Update Posted: 2025-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 509

Inclusion Criteria

• All adult (≥ 18 years) ambulatory patients of both sexes with a diagnosis of HFrEF (LVEF≤ 40%) and NYHA class II-IV under optimized medical therapy who are presented to the outpatient clinic and started spironolactone at the time of enrollment.

Exclusion Criteria

• Pregnancy or breastfeeding
• Serum creatinine > 2.5 mg/dL (221 µmol/L) in males and > 2 mg/dL (177 µmol/L) in women (or estimated glomerular filtration rate (eGFR) ≤ 30 mL/minute/1.73 m2)
• Hyperkalemia (serum potassium level > 5 mEq/L)
• Renal transplantation
• Concomitant administration of potent CYP3A inhibitors
• Concomitant administration of potassium supplements or potassium-sparing diuretics
• Disorders of the adrenal glands (such as Addison disease).
• Patients who used MRA in the last 2 weeks before enrollment.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
The Female Group	Spironolactone	Patients identified themselves as females (Apparent gender)
The Male Group	Spironolactone	Patients identified themselves as males (Apparent gender)

Primary Outcome Measures

Name	Time	Method
HF Hospitalization	6 months after enrollment	The event of hospitalization due to heart failure.

Secondary Outcome Measures

Name	Time	Method
Hospitalization	6 months after enrollment	The event of hospitalization due to any cause.
All-cause mortality	6 months after enrollment	The event of mortality due to any cause.

Trial Locations

Locations (1)

King Fahd Central Hospital; 🇸🇦 Al 'Usaylah, Saudi Arabia