Ongoing Clinical Trials for Heart Failure with Preserved Ejection Fraction
Currently, there are 9 clinical trials investigating new treatments for heart failure with preserved ejection fraction. These studies are taking place across multiple European countries and are testing various medications including colchicine, sertraline, dapagliflozin, trimetazidine, and several experimental drugs. The trials aim to improve symptoms, reduce hospitalizations, and enhance quality of life for patients with this challenging heart condition.
Clinical trial locations
- Belgium
- Bulgaria
- Czechia
- Denmark
- Germany
- Hungary
- Italy
- Netherlands
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Poland
- Study on the Effects of Sertraline on Anxiety and Depression in Heart Failure Patients with Preserved Ejection Fraction
- Study on the Effects of Trimetazidine on Heart Failure with Preserved Ejection Fraction in Patients
- Study of LY3540378 for Adults with Worsening Chronic Heart Failure with Preserved Ejection Fraction
- Study on the Safety and Effectiveness of Tovinontrine for Adults with Chronic Heart Failure with Preserved Ejection Fraction
- Study on the Safety and Tolerability of BMS-986435 in Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)
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Spain
- Study on the Effects of Dapagliflozin for Patients with Heart Failure with Preserved Ejection Fraction
- Study of LY3540378 for Adults with Worsening Chronic Heart Failure with Preserved Ejection Fraction
- Study on the Safety and Effectiveness of Tovinontrine for Adults with Chronic Heart Failure with Preserved Ejection Fraction
- Study on the Safety and Tolerability of BMS-986435 in Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)
- Sweden
Study on the Effects of Colchicine for Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)
This trial, conducted in Denmark, is investigating whether colchicine can improve health status and symptoms for people with this condition. Colchicine is an anti-inflammatory medication that has been used for many years to treat other conditions involving inflammation.
Main inclusion criteria: Participants must be 40 years or older with a left ventricular ejection fraction of 45% or higher. They should have experienced heart failure symptoms for at least 30 days and be classified as NYHA functional class II-IV. Evidence of heart structure problems such as left atrial enlargement or left ventricular hypertrophy must be present on echocardiogram. Blood tests should show pro-BNP levels of 125 pg/ml or higher in normal rhythm, or 300 pg/ml or higher with atrial fibrillation. Body mass index must be less than 40 kg/m².
Main exclusion criteria: Patients with different types of heart failure, those outside the specified age range, vulnerable populations, and those not meeting specific health criteria are excluded from participation.
Focus of the trial: The study aims to evaluate how colchicine affects the health status of people living with this condition over a six-month period. Researchers will use the Kansas City Cardiomyopathy Questionnaire to measure changes in how heart failure affects daily life. The trial will look at improvements in heart failure symptoms and overall health status.
Investigational drug: Colchicine (brand name Colrefuz) is taken as an oral tablet. It works by reducing inflammation and may improve heart function through its effects on cellular processes.
Study on the Effects of Sertraline on Anxiety and Depression in Heart Failure Patients with Preserved Ejection Fraction
This Polish trial is examining whether sertraline, a commonly used antidepressant, can help reduce anxiety and depression symptoms in patients with this heart condition. The study also explores whether the medication might have beneficial effects on heart health markers.
Main inclusion criteria: Participants must be between 60 and 84 years old and score 10 or higher on either the Patient Health Questionnaire (PHQ-9) for depression or the Generalized Anxiety Disorder (GAD-7) scale for anxiety. They must have a documented diagnosis of the condition or receive a new diagnosis based on HFA-PEFF criteria during screening.
Main exclusion criteria: People with severe kidney disease, severe liver disease, recent heart attack (within 3 months), uncontrolled high blood pressure, recent stroke (within 6 months), active cancer, severe unstable mental health disorders, pregnancy or breastfeeding, current participation in another trial, or known allergy to the study medication cannot participate.
Focus of the trial: The study will monitor participants over time to assess whether sertraline reduces anxiety and depressive symptoms while potentially improving blood vessel function and heart-related health markers. Researchers are also interested in whether the medication can reduce the risk of hospitalization for cardiovascular reasons or death.
Investigational drug: Sertraline (brand name Asentra) is administered as a 50 mg film-coated tablet taken orally. It is a selective serotonin reuptake inhibitor that works by increasing serotonin levels in the brain, which helps improve mood and reduce anxiety.
Study on the Effects of Dapagliflozin for Patients with Heart Failure with Preserved Ejection Fraction
This Spanish study is investigating how dapagliflozin, a medication originally developed for diabetes, affects heart function and structure in patients with this condition. The trial uses advanced imaging techniques to understand the biological effects of the medication.
Main inclusion criteria: Adults aged 18 or older with a left ventricular ejection fraction of 50% or higher can participate. Participants must have a diagnosis of the condition and a history of hospitalization or intravenous diuretic treatment in the last 6 months. Evidence of diastolic dysfunction must be present on echocardiogram. Participants must be clinically stable for more than 1 month and have a clinical indication for cardiac catheterization and to start SGLT2 inhibitor treatment.
Main exclusion criteria: The specific exclusion criteria focus on participants who don’t meet the required age range, clinical trial groups not included in the study, or belong to vulnerable populations.
Focus of the trial: The study explores how dapagliflozin affects the heart’s ability to relax and contract, as well as changes in heart size and shape. Researchers will use MRI and echocardiography to examine these changes, including cellular-level changes such as heart muscle cell stiffness.
Investigational drug: Dapagliflozin (brand name Forxiga) is a 10 mg film-coated tablet taken orally once daily. It is an SGLT2 inhibitor that works by helping the kidneys remove glucose from the bloodstream through urine, which may provide cardiovascular benefits beyond blood sugar control.
Study on the Effects of Trimetazidine on Heart Failure with Preserved Ejection Fraction in Patients
This Polish trial is studying trimetazidine, a metabolic agent that helps improve energy production in heart cells, to see whether it can reduce hospitalizations and improve outcomes for patients with the condition.
Main inclusion criteria: Participants must be between 55 and 85 years old with NYHA Class I to III symptoms. They must have a documented diagnosis or receive a new diagnosis with an HFA-PEFF score of 5 or higher. Left ventricular ejection fraction must be 50% or higher on echocardiogram. No changes in heart failure medication should have occurred for at least 3 months before screening, and high-sensitivity C-reactive protein (hsCRP) levels must be 1.5 mg/L or higher.
Main exclusion criteria: People with severe allergic reactions to study medications, recent heart attack (within 3 months), uncontrolled high blood pressure, severe kidney or liver disease, current participation in another trial, pregnancy or breastfeeding, or other serious medical conditions that might interfere with results are excluded.
Focus of the trial: The study monitors participants until the end of 2027 to observe time to hospitalization or serious health events. Researchers will measure various health indicators including heart function and blood markers linked to heart health and inflammation.
Investigational drug: Trimetazidine dihydrochloride (brand name Trimeductan MR) is a 35 mg modified-release tablet taken orally. It works as a metabolic agent by optimizing energy production in heart cells, helping them function more efficiently under stress.
Study of LY3540378 for Adults with Worsening Chronic Heart Failure with Preserved Ejection Fraction
This multi-country trial (Poland, Spain, Hungary, and Czechia) is investigating LY3540378, an experimental protein-based treatment given by injection, to see if it can improve atrial myopathy, a condition affecting the upper chambers of the heart.
Main inclusion criteria: Adults aged 18 or older with chronic heart failure and preserved ejection fraction can participate. The trial is open to both men and women with worsening symptoms.
Main exclusion criteria: People with other serious medical conditions that might interfere with the study, recent heart attack or stroke, severe kidney or liver disease, pregnancy or breastfeeding, current participation in another trial, history of drug or alcohol abuse, allergy to the study medication, mental health conditions that might interfere with participation, or inability to comply with study procedures are excluded.
Focus of the trial: The study aims to determine if LY3540378 is more effective than a placebo in improving atrial myopathy. Researchers will measure Left Atrial Reservoir Strain (LARS) to evaluate how well the heart is functioning. The trial is double-blind to ensure unbiased results.
Investigational drug: LY3540378 is a solution for injection administered under the skin. It is a specially designed protein treatment currently in the investigational stage.
Study of spironolactone and eplerenone in patients with heart failure with preserved ejection fraction (HFpEF)
This Swedish registry-based study compares two aldosterone antagonist medications—spironolactone and eplerenone—to determine if they help reduce hospitalizations and prevent deaths in patients with the condition.
Main inclusion criteria: Participants must be 50 years or older with stable heart failure symptoms (NYHA Class II-IV). Left ventricular ejection fraction must be 40% or higher. Elevated natriuretic peptide levels are required: NT-proBNP above 300 ng/L (or BNP above 100 pg/mL) for normal rhythm, above 750 ng/L (or BNP above 250 pg/mL) for irregular heartbeat, or above 1200 ng/L (or BNP above 400 pg/mL) within the past 12 months. Participants must regularly use loop diuretics and provide written informed consent.
Main exclusion criteria: People under 18 years, those with known allergic reactions to the medications, current use of these medications, severe kidney disease, high potassium levels, severe liver disease, pregnancy or planning pregnancy, breastfeeding, low blood pressure (below 90 mmHg), use of other potassium-increasing medications, participation in another trial, inability to provide consent, life expectancy less than 12 months, Addison’s disease, or history of serious side effects from similar medications are excluded.
Focus of the trial: The study examines whether adding spironolactone or eplerenone to standard treatment helps reduce hospitalizations and deaths from heart-related causes. The treatment period may last up to 120 days, with follow-up continuing until December 2027.
Investigational drugs: Both spironolactone and eplerenone are aldosterone antagonists taken orally as tablets at doses up to 50 mg daily. They work by blocking hormones that cause salt and fluid retention in the body, helping to reduce strain on the heart.
Study on the Effect of Empagliflozin, Acetylcholine Chloride, Insulin Aspart, and Sodium Nitroprusside Dihydrate on Heart Failure with Preserved Ejection Fraction Patients
This Dutch trial is investigating whether empagliflozin, an SGLT-2 inhibitor, can improve blood flow in small blood vessels in the skin, which may reflect improvements in overall circulation for patients with the condition.
Main inclusion criteria: Participants must have a diagnosis according to the 2021 European Society of Cardiology guidelines, be able to understand and speak Dutch, have a plan to start treatment with empagliflozin 10mg once daily, and provide signed informed consent. Both men and women aged 18 and older can participate.
Main exclusion criteria: People with other serious heart conditions besides the studied condition, severe kidney problems, uncontrolled high blood pressure, recent heart attack (within 3 months), severe liver disease, history of severe allergic reactions to the study medication, pregnancy or breastfeeding, participation in another trial within 30 days, history of drug or alcohol abuse in the past year, or any condition making participation unsafe are excluded.
Focus of the trial: The study evaluates how empagliflozin affects the function of small blood vessels in the skin after three months of treatment. Researchers use laser speckle contrast analysis to measure blood flow in the forearm skin, with additional substances applied to assess microvascular response.
Investigational drug: Empagliflozin is a 10 mg film-coated tablet taken orally once daily. It is an SGLT-2 inhibitor that works by helping the kidneys remove excess glucose from the blood, potentially improving circulation and reducing the workload on the heart.
Study on the Safety and Effectiveness of Tovinontrine for Adults with Chronic Heart Failure with Preserved Ejection Fraction
This large multi-country trial (Netherlands, Hungary, Germany, Poland, Bulgaria, Czechia, Spain, Belgium, and Italy) is studying tovinontrine, a phosphodiesterase type 9 inhibitor, to see if it can lower NT-proBNP levels, a blood marker often elevated in heart failure.
Main inclusion criteria: Adults aged 18 or older with a medical history showing clinical heart failure (NYHA functional class II to III) for at least 6 months can participate. Ejection fraction must be greater than 40% with left atrial enlargement visible on echocardiogram. NT-proBNP levels must be 300 pg/mL or higher (500 pg/mL or higher with atrial fibrillation or flutter). Participants must be on stable doses of guideline-recommended heart failure medication for at least 4 weeks, with no new medications (except diuretics) started within 3 months before screening.
Main exclusion criteria: People with other serious heart conditions unrelated to chronic heart failure, recent heart attack or stroke (within 3 months), severe kidney disease or dialysis, severe liver disease, pregnancy or breastfeeding, participation in another trial within 30 days, history of drug or alcohol abuse in the past year, or any condition making participation unsafe are excluded.
Focus of the trial: The 12-week study evaluates how tovinontrine affects NT-proBNP levels and other health indicators. Participants undergo regular monitoring including measurements of this heart-related protein, symptom assessments using specific questionnaires, and evaluations of quality of life.
Investigational drug: Tovinontrine is taken as an oral tablet. It is a phosphodiesterase type 9 inhibitor currently in the investigational stage, being studied for its potential to improve heart function and reduce NT-proBNP levels.
Study on the Safety and Tolerability of BMS-986435 in Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)
This trial in Italy, Poland, and Spain is evaluating BMS-986435/MYK-224, a new experimental treatment, to understand its safety and how well patients tolerate it when living with this condition.
Main inclusion criteria: Adults aged 18 or older with stable, symptomatic heart failure and normal heart pumping ability can participate. Both men and women are eligible.
Main exclusion criteria: People with a history of severe allergic reactions to the medication or its ingredients, other serious heart conditions unrelated to the studied condition, severe kidney or liver disease, recent heart attack or stroke (within 6 months), current participation in another trial, pregnancy or breastfeeding, uncontrolled high blood pressure, history of drug or alcohol abuse within the past year, cancer diagnosis in the past 5 years (except certain skin cancers), or any medical condition making participation unsafe are excluded.
Focus of the trial: The study monitors participants to understand the safety and tolerability of MYK-224. Researchers track side effects and measure drug levels in the bloodstream to understand how the body processes the medication. The trial is expected to conclude in early 2025.
Investigational drug: BMS-986435/MYK-224 is taken as an oral tablet. It is a cardiac modulator currently being investigated for its potential to help manage this condition by modulating cardiac muscle function.
Summary
These nine clinical trials represent diverse approaches to treating heart failure with preserved ejection fraction. The studies are concentrated primarily in European countries, with Poland hosting the most trials (five), followed by Spain (four) and multiple trials in the Netherlands, Hungary, Czechia, and Italy. Several trials focus on repurposing existing medications—colchicine, sertraline, dapagliflozin, empagliflozin, spironolactone, and eplerenone—while others investigate novel experimental compounds like LY3540378, tovinontrine, and BMS-986435.
A notable trend is the investigation of SGLT2 inhibitors (dapagliflozin and empagliflozin), which were originally developed for diabetes management but are now showing promise for cardiovascular benefits. The trials also reflect different approaches to understanding the condition, from examining mental health impacts (sertraline study) to investigating cellular-level changes in heart muscle and blood vessel function.
Most trials require participants to have an ejection fraction of 40-50% or higher and elevated natriuretic peptide levels, confirming the diagnosis through standardized criteria. The studies typically exclude people with severe kidney or liver disease, recent cardiovascular events, or uncontrolled blood pressure, ensuring participant safety while focusing on the target population.
