SGLT2i and KNO3 in HFpEF - The SAK HFpEF Trial
Recruiting now · Phase 2 · Has a placebo group
Conditions studied: Heart Failure With Preserved Ejection Fraction
In brief
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).
Key facts
- Study ID
- NCT05138575
- Run by
- University of Pennsylvania
- People needed
- 53
- Starts
- 2022-01-24
- Expected to finish
- 2027-05-31
- Last updated by the study team
- 2026-04-16
Who can join
Age: 18 and older. Sex: any. Healthy volunteers: not accepted.
You may not qualify if…
- Age <18 years old
- Pregnancy: Women of childbearing potential will undergo a urine pregnancy test during the screening visit.
- Treatment with organic nitrates or phosphodiesterase inhibitors that cannot be interrupted
- Uncontrolled atrial fibrillation, as defined by a resting atrial fibrillation heart rate > 100 beats per minute at the time of the baseline assessment
- Hemoglobin < 10 g/dL
- Subject inability/unwillingness to exercise
- Moderate or greater left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), mild or greater mitral stenosis, severe right-sided valvular disease
- Known hypertrophic, infiltrative, or inflammatory cardiomyopathy
- Clinically significant pericardial disease, as per investigator judgment
- Current angina due to clinically significant epicardial coronary disease, as per investigator judgment
- Acute coronary syndrome or coronary intervention within the past 2 months
- Primary pulmonary artery hypertension (WHO Group 1 Pulmonary Arterial Hypertension)
- Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease Stage III or greater GOLD criteria (FEV1<50%), treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, current use of supplemental oxygen aside from nocturnal oxygen for the treatment of obstructive sleep apnea.
- Desaturation to <90% on the baseline maximal effort cardiopulmonary exercise test will also be grounds for exclusion
- Clinically-significant ischemia, as per investigator's judgement, on stress testing without either (1) subsequent revascularization, (2) an angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgment; (3) a follow-up 'negative' stress test, particularly when using a more specific technique (i.e., a negative perfusion imaging test following a 'positive' ECG stress test)
- Exercise-induced regional wall motion abnormalities on the echocardiographic assessment during the baseline maximal effort cardiopulmonary exercise test will also be exclusionary
- Left ventricular ejection fraction < 45% on a prior echocardiogram or cardiac MRI, unless the reduced LVEF occurred within the context of an uncontrolled supraventricular arrhythmia, with return of a normal ejection fraction following treatment of the arrhythmia
- Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x ULN, Albumin < 3.0 g/dL)
- eGFR < 30 mL/min/1.73m2.
- Methemoglobin > 5%
- Serum potassium > 5.0 mEq/L on baseline testing
- Type I Diabetes
- History of ketoacidosis
- Current use of, or prior intolerance to, an SGLT2i
- Ongoing maintenance of a 'Ketogenic Diet' (low carbohydrate, high fat)
Where it is running
- University of Pennsylvania Health System — Philadelphia, Pennsylvania, United States (enrolling)
Full record on ClinicalTrials.gov
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