Actively Recruiting
SGLT2i and KNO3 in HFpEF - The SAK HFpEF Trial
Led by University of Pennsylvania · Updated on 2026-04-16
53
Participants Needed
1
Research Sites
279 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This study will test whether pharmacologic agents that may improve mitochondrial function and energy fuel metabolism \[Empagliflozin (Empa)\], with and without additional supplements that increase perfusion and fatty acid oxidation \[Potassium Nitrate (KNO3)\], improve submaximal exercise endurance and skeletal muscle oxidative phosphorylation capacity (SkM OxPhos) in participants with Heart Failure with Preserved Ejection Fraction (HFpEF).
CONDITIONS
Official Title
SGLT2i and KNO3 in HFpEF - The SAK HFpEF Trial
Who Can Participate
Eligibility Criteria
You may qualify if you...
- NYHA Class II-III symptoms
- Left ventricular ejection fraction of 50% or higher
- Stable medical condition for at least 2 weeks as judged by the investigator
- Prior or current evidence of elevated heart filling pressures shown by at least one of the following:
- Mitral early/septal tissue annular velocity ratio above 8 with low septal or lateral e' velocities plus one of:
- Large left atrium (volume index over 34 mL/m2)
- Chronic loop diuretic use for symptoms
- Elevated natriuretic peptides in the past year (NTproBNP over 125 pg/mL in sinus rhythm or over 375 pg/mL in atrial fibrillation)
- Mitral E/e' ratio over 14 at rest or during exercise
- Previously elevated filling pressures measured invasively or prior acute heart failure episode requiring IV diuretics
- Mitral early/septal tissue annular velocity ratio above 8 with low septal or lateral e' velocities plus one of:
You will not qualify if you...
- Age under 18 years
- Pregnancy or women of childbearing potential without a negative pregnancy test
- Use of organic nitrates or phosphodiesterase inhibitors that cannot be stopped
- Uncontrolled atrial fibrillation with resting heart rate over 100 bpm
- Hemoglobin below 10 g/dL
- Inability or unwillingness to exercise
- Moderate or severe left-sided valvular disease or severe right-sided valvular disease
- Known hypertrophic, infiltrative, or inflammatory heart muscle disease
- Significant pericardial disease
- Current angina due to major coronary artery disease
- Acute coronary event or intervention within past 2 months
- Primary pulmonary artery hypertension
- Significant lung disease including severe COPD or recent steroid use
- Oxygen use except for sleep apnea
- Exercise-induced oxygen desaturation below 90%
- Significant ischemia without proper treatment or clearance
- Left ventricular ejection fraction below 45% unless reversible
- Significant liver disease affecting function
- Kidney function below eGFR 30 mL/min/1.73m2
- Methemoglobin level over 5%
- High serum potassium above 5.0 mEq/L
- Type 1 diabetes or history of ketoacidosis
- Current or prior intolerance to SGLT2 inhibitors
- Following a ketogenic diet
- Allergy to beets
- Severe right heart dysfunction
- Blood pressure over 180 mmHg or under 100 mmHg at rest
- Abnormal blood pressure response on standing
- Participation in another investigational drug study
- Any condition that might interfere with study completion, including serious medical or psychiatric issues or travel difficulties
AI-Screening
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Trial Site Locations
Total: 1 location
1
University of Pennsylvania Health System
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
Research Team
M
Melissa Fernando
CONTACT
C
Cassandra Demastus, CRNP
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
TREATMENT
Number of Arms
3
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