NCT05138575RecruitingPhase 2

SGLT2i and KNO3 in HFpEF - The SAK HFpEF Trial

Source: ClinicalTrials.gov · Last updated 16 Apr 2026

Brief summary (registry, in English)

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).

Status (registry): Recruiting
Phase (registry): Phase 2
Study type: Interventional
Enrollment: 53 (estimated)
First submitted: 3 Nov 2021
Start date: 24 Jan 2022
Primary completion date: 31 May 2027
Lead sponsor: University of Pennsylvania
Diseases: Heart failure
NCT number: NCT05138575

What you commit to

Study type: Interventional · Phase 2
Planned participants: 53
From 24 Jan 2022 to the primary completion date, 31 May 2027
1 site in 1 country
Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

Treatment with organic nitrates or phosphodiesterase inhibitors that cannot be interrupted
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
Current use of, or prior intolerance to, an SGLT2i
Active participation in another study that utilizes an investigational agent (observational studies/registries allowed)

Other illness

Uncontrolled atrial fibrillation, as defined by a resting atrial fibrillation heart rate \> 100 beats per minute at the time of the baseline assessment
Moderate or greater left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), mild or greater mitral stenosis, severe right-sided valvular disease
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 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
Type I Diabetes
History of ketoacidosis
Allergy to beets
Any condition that, in the opinion of the investigator, may interfere with the completion/performance of the study. This may include comorbid or psychiatric conditions that may impede successful completion of the protocol, or logistical concerns (e.g., inability to travel to the exercise unit).

Lab values

Hemoglobin \< 10 g/dL
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.
Serum potassium \> 5.0 mEq/L on baseline testing

Age

Age \<18 years old

Other

Pregnancy: Women of childbearing potential will undergo a urine pregnancy test during the screening visit.
Subject inability/unwillingness to exercise
Known hypertrophic, infiltrative, or inflammatory cardiomyopathy
Methemoglobin \> 5%
Ongoing maintenance of a 'Ketogenic Diet' (low carbohydrate, high fat)
Severe right ventricular dysfunction
Baseline resting seated systolic blood pressure \> 180 mmHg or \< 100 mmHg
Persistently low or high seated blood pressure or orthostatic blood pressure response to the transition from supine to standing (\>20 mmHg reduction in systolic blood pressure 2-3 minutes after standing, or a fall in SBP to \< 90 mmHg) at the baseline visit

Criteria the registry did not label

Inclusion:
1\. NYHA Class II-III symptoms 2. Left ventricular ejection fraction \>= 50% 3. Stable medical condition for at least 2 weeks, as per investigator judgment 4. Prior or current evidence for elevated filling pressures, as evidenced by at least one of the following:
Mitral early (E)/septal tissue annular (e') velocity ratio \> 8, in the context of a septal e' velocity \<=7 cm/s or a lateral e' \<= 10 cm/s, in addition to one of the following: i. Large left atrium (LA volume index \> 34 mL/m2) ii. Chronic loop diuretic use for control of symptoms iii. Elevated natriuretic peptides within the past year (e.g., NTproBNP \> 125 pg/mL in sinus rhythm or \> 375 pg/mL if in atrial fibrillation) b. Mitral E/e' ratio \> 14 at rest or during exercise c. Elevated invasively-determined filling pressures previously (resting left ventricular end-diastolic pressure \>= 16 mm Hg or pulmonary capillary wedge pressure \>= 15 mmHg; or PCWP/LVEDP \>= 25 mmHg with exercise) d. Prior episode of acute heart failure requiring IV diuretics

Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (1)

Sites in registry order. Pick your city on the disease page to sort them by distance.

Site	City	Country	Site status
University of Pennsylvania Health System Coordinator of this site? Confirm its status	Philadelphia	United States	Recruiting

This page is information, not medical advice. Discuss any trial with your doctor.