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

Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05139472
• Other study ID #: STU 2018-0311
• Status: Completed
• Phase: Phase 3
• Start date: November 9, 2021
• Est. completion date: February 19, 2024

Study information

• Verified date: February 2024
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: February 19, 2024
• Est. primary completion date: September 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Heart Failure, Diastolic

Intervention

Drug:
• Empagliflozin 10 MG
Daily Empagliflozin

Locations

Country	Name	City	State
United States	Institute for Exercise and Environmental Medicine	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Oxygen Uptake	Peak VO2 measured on maximal exercise test	12 weeks
Primary	Peak Pulmonary Capillary Wedge Pressure (PCWP)	Peak PCWP, measured at end-expiration, at the end of maximal exercise test	12 weeks
Secondary	Primary Endpoints after single dose of empagliflozin	Peak VO2 and peak PCWP will be measured after a single dose of empagliflozin	1 hour
Secondary	Cardiac Output at Rest and During Exercise		12 weeks
Secondary	Stroke Volume at Rest and During Exercise		12 weeks
Secondary	Right Atrial Pressure at Rest and During Exercise		12 weeks
Secondary	Pulmonary Capillary Wedge Pressure at Rest and During Submaximal Exercise		12 weeks
Secondary	Left ventricular volumes at rest and during submaximal exercise	Measured by echocardiography	12 weeks
Secondary	Hemoglobin mass, plasma volume, total blood volume	Measured by Carbon Monoxide Rebreathe	12 weeks
Secondary	Diastolic parameters at rest and during submaximal exercise	Measured by echocardiography	12 weeks
Secondary	6 minute walk time		12 weeks