Impact of Empagliflozin on Functional Capacity in Heart Failure With Preserved Ejection Fraction

Phase 3

Completed

• Conditions: Heart Failure with Preserved Ejection Fraction; Heart Failure, Diastolic; Diabetes Mellitus
• Interventions: Drug: Empagliflozin 10 MG

• Registration Number: NCT05139472
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitors generally and empagliflozin specifically have shown cardiovascular benefits in patients with heart failure (HF), but the underlying mechanisms remain unclear. Empagliflozin use resulted in lower pulmonary artery diastolic pressures in patients with HF, suggesting a beneficial diuretic effect. Other potential mechanisms include increased blood volume, decreased blood pressure, and changes in sympathetic and neuro-hormonal activation.

This study is a single-arm, open label, prospective interventional study of 8 subjects with heart failure with preserved ejection fraction (HFpEF). Before and after 12 weeks of daily empagliflozin, participants with undergo comprehensive invasive exercise testing with a right heart catheter. Our goal is to evaluate the effects of empagliflozin on fitness, assessed by peak VO2, and peak left ventricular filling pressure, assessed by pulmonary capillary pressure at peak exercise.

Detailed Description

This is a single-arm, open label, pilot study of 8 subjects with HFpEF. The subjects will undergo screening tests (exercise stress echo and blood work) to evaluate for potential exclusion criteria and provide familiarization to the exercise protocol. Those included will undergo an echocardiogram and invasive cardiopulmonary exercise test. This involves placement of a right heart catheter in the pulmonary artery and undergoing seated, upright exercise. During the exercise test, the subject's oxygen uptake (VO2), intra-cardiac pressures (right atrial pressure, pulmonary capillary wedge pressure) and cardiac output (Qc) will be measured. The subject will take a dose of empagliflozin in the lab and wait for at least 60 minutes. They will repeat a shortened version of the exercise test in the afternoon. After baseline testing, each subject will take 10mg empagliflozin daily for 12 weeks. They will have repeat blood work (specific electrolytes and renal function) 30 days after starting medication to screen for renal injury. After 12 weeks, they will return for another invasive cardiopulmonary exercise test and echocardiogram.

Study Timeline

• Study Start: 2021-11-09
• Study First Submitted: 2021-11-10
• Study First Submitted QC: 2021-11-17
• Study First Posted: 2021-12-01
• Primary Completion: 2023-09-20
• Status Verified: 2024-02
• Study Completion: 2024-02-19
• Last Update Submitted: 2024-02-26
• Last Update Posted: 2024-02-28
• Disposition First Submitted: 2024-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

• adults ages 50-85
• clinical heart failure
• ejection fraction > 50%

Exclusion Criteria

• previous hypersensitivity or adverse reaction to SGLT-2 inhibitors
• currently treated with SGLT-2 inhibitor
• current or prior ejection fraction <50%
• chronic kidney disease with glomerular filtration rate < 45 ml/kg/min
• unstable coronary artery disease
• significant arrhythmia
• BMI >55 kg/m2
• inability to exercise.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Empagliflozin 10 MG	This arm of the study will take 10 mg empagliflozin daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Peak Oxygen Uptake	12 weeks	Peak VO2 measured on maximal exercise test
Peak Pulmonary Capillary Wedge Pressure (PCWP)	12 weeks	Peak PCWP, measured at end-expiration, at the end of maximal exercise test

Secondary Outcome Measures

Name	Time	Method
Left ventricular volumes at rest and during submaximal exercise	12 weeks	Measured by echocardiography
Pulmonary Capillary Wedge Pressure at Rest and During Submaximal Exercise	12 weeks
6 minute walk time	12 weeks
Primary Endpoints after single dose of empagliflozin	1 hour	Peak VO2 and peak PCWP will be measured after a single dose of empagliflozin
Cardiac Output at Rest and During Exercise	12 weeks
Stroke Volume at Rest and During Exercise	12 weeks
Right Atrial Pressure at Rest and During Exercise	12 weeks
Hemoglobin mass, plasma volume, total blood volume	12 weeks	Measured by Carbon Monoxide Rebreathe
Diastolic parameters at rest and during submaximal exercise	12 weeks	Measured by echocardiography

Trial Locations

Locations (2)

Institute for Exercise and Environmental Medicine; 🇺🇸 Dallas, Texas, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States