Clinical Research Directory

Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction

The purpose of this study is to find out if the investigational drug called omecamtiv mecarbil can reduce the risk of the effects of heart failure, like hospitalization, transplantation, or death in patients with heart failure and severely reduced ejection fraction.

Implementation and Interaction of Clinician And Patient-facing Tools Aiming to Intensify Neurohormonal Medicines for Heart Failure

An increasing number of guideline-directed medical therapies (GDMT) have been developed for patients with chronic heart failure with reduced ejection fraction (HFrEF). When used in combination at recommended doses, patients often experience significant improvements in cardiac function, quality of life, and survival.1,2 However, GDMT underuse occurs for the vast majority of patients with HFrEF. Two recent trials demonstrated improved GDMT prescribing during a clinic visit, each using automated delivery of a patient-centered decision support tool to promote a proactive and holistic approach to prescribing: EPIC-HF (NCT03334188) tested a brief video and checklist document sent to patients just prior to a clinic visit encouraging them to work with their clinicians to make at least 1 positive change to their GDMT; PROMPT-HF (NCT05433220) tested tailored electronic health record (EHR) alerts for GDMT intensification delivered to clinicians during clinic visits. The current I-I-CAPTAIN-HF study aims to broadly implement and test the EPIC-HF patient-facing and PROMPT-HF clinician-facing tools for HFrEF medication intensification at 5 health systems around the country through a pragmatic cluster-randomized implementation-effectiveness trial. This will occur through an initial phase of adaptation of the 2 tools at each health system. Once ready, the 2 tools will be tested using a 2x2 randomization at the clinician-level. In parallel, formal assessment of the implementation of EPIC-HF and PROMPT-HF will work to understand the most effective means of intervention design and delivery, as well as adaptations due to contextual factors to optimize use.

Lumacaftor Yields Reversal of Impaired Cerebral Blood Flow in Heart Failure Patients

Cognitive impairment (CI) is highly prevalent in patients with heart failure with reduced ejection fraction (HFrEF), which has significant implications for disease management, quality of life and clinical outcomes. Currently, there are no specific treatments for CI aside from the current standard of care therapy for HF, making this a high unmet medical need. Impaired cerebral autoregulation is a proposed mechanistic factor that leads to cerebral hypoperfusion, ischemic damage and the development for CI. Preclinical data indicates that restoring CFTR-protein expression normalizes cerebral microvascular function and cerebral blood flow (CBF) in models of HF. The purpose of this study is to investigate whether CFTR-targeting therapy enhances cerebral perfusion and cognitive function in heart failure patients using the CFTR-corrector Lumacaftor.

Emulation of the EMPEROR-Reduced Trial Using Healthcare Claims Data

Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Treatment of Non-ischemic Cardiomyopathies by Intravenous Extracellular Vesicles of Cardiovascular Progenitor Cells

The goal of this clinical trial is to assess the safety and efficacy of three intravenous injections of the extracellulat vesicle-enriched secretome of cardiovascular progenitor cells in severely symptomatic patients with drug-refractory left ventricular (LV) dysfunction secondary to non-ischemic dilated cardiomyopathy. The main questions it aims to answer are: * Are these repeated injections safe and well tolerated? * Do they improve cardiac function and, if yes, to what extent?

A Safety and Tolerability Study of HJB647 in Heart Failure Participants With Reduced Ejection Fraction

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of HJB647 at two different doses in participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).

A Randomized Placebo-procedure Controlled Trial of the Enhancor System (PULmonary Artery Denervation) to Evaluate Safety and Efficacy in Patients With Combined Pre- and Post-capillary Pulmonary Hypertension Associated With Left Heart Disease

The goal of this clinical study is to evaluate the safety and efficacy of percutaneous pulmonary artery denervation with the Multi-Pole Pulmonary Artery Radiofrequency Ablation Enhancor System in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) associated with left heart disease (LHD). This randomized control trial will compare the investigational device (The Enhancor System) to control (medical therapy.) Participants who will consist of patients with chronic heart failure (HF) who are receiving maximally tolerated guideline-directed medical therapy (GDMT) for left heart failure, are clinically stable, and who have been diagnosed with CpcPH by right heart catheterization (RHC), will be treated with PADN and followed for 3 years.

A Real-world Study of Clinical Treatment Guidelines for Patients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan

The aim of this study was to describe the real-world clinical profile, treatment patterns, and guideline alignment of patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan in routine clinical practice in Romania. The study used secondary use of data, with all analyses conducted on anonymized, pre-existing data collected for routine clinical and administrative purposes.

Mechanistic Clinical Trial Comparing the Pharmacokinetics/Pharmacodynamics of Metoprolol in Heart Failure With Reduced Ejection Fraction Patients With Low vs. High Polygenic Score

The purpose of this trial is to better understand how the beta-blocker metoprolol works in people with Heart Failure with Reduced Ejection Fraction (HFrEF) according to participants genetics. Participants will have the beta-blocker (BB) polygenic score calculated from genotype data. The score will be used to stratify the patients in the low and high polygenic score groups in the study. The hypotheses for this trial are: * HFrEF patients with high polygenic score will have weaker cardiovascular responses to metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score have lower steady-state plasma concentrations of metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score require higher metoprolol succinate plasma concentrations to achieve similar cardiovascular effects as those with low polygenic score.

The CardioClip Study

The CardioClip study is exploring the use of a wireless sensor to monitor pressure in the pulmonary artery. This sensor is inserted much like the mTEER procedure, a non-surgical method through a vein in the groin. The investigators want to find out if the sensor, by constantly sending information about heart function, can help improve patient outcomes. This means doctors could adjust medications based on real-time pressure changes detected by the sensor. The results from this study will help pave the way for future trials, asking if using these wireless sensors could benefit people with valve disease and heart failure.

STEPwise De-escalation and Optimizing Withdrawal of ARNI and SGLT2i in Normalized Heart Failure

This is a multicenter, randomized, open-label pilot study to evaluate whether stepwise withdrawal of two heart failure medications-angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitor (SGLT2i)-is safe in patients with Heart Failure with improved Ejection Fraction (HFimpEF) whose underlying structural cause (valvular heart disease or ischemic cardiomyopathy) has been completely corrected by surgery or intervention. Eighty adult patients (40 per arm) whose left ventricular ejection fraction (LVEF) has recovered to 50% or higher and whose NT-proBNP is ≤ 250 ng/L will be randomized 1:1 to either (1) stepwise withdrawal of ARNI followed by SGLT2i over one month under close echocardiographic monitoring, or (2) continuation of their current guideline-directed medical therapy. The primary outcome is the change in LVEF at 12 months, with non-inferiority of the withdrawal strategy declared if the LVEF decline is within 5 percentage points of the continuation arm. Secondary outcomes include cardiovascular death, heart failure hospitalization, NT-proBNP, quality of life (KCCQ-12), 6-minute walk distance, and adverse events. Results from this pilot will inform the design and sample size of a subsequent definitive non-inferiority trial and may provide initial evidence to guide deprescribing decisions in clinical practice.

Effect of Weight Loss on Physical and Cardiac Performance in People With Obesity and Heart Failure

The benefit of weight loss in patients with obesity and heart failure with reduced ejection fraction (HFrEF) is controversial. Semaglutide has shown cardiovascular (CV) risk-reduction and impact on CV risk factors including overweight, dysglycaemia and hypertension in subjects with type 2 diabetes (T2D). The STEP-HFpEF (Semaglutide Treatment Effect in People With Obesity and HFpEF) recently demonstrated, at 1-year, to not only reduce weight considerably, but also significantly improve health-related quality of life, functional status scores and 6-min walk distance in patients with heart failure with preserved ejection fraction (HFpEF). Also, the recently concluded SELECT trial was the first CV outcome trial with semaglutide in patients with overweight or obesity and established CV disease, including heart failure (but no T2D). Semaglutide demonstrated a 20% reduction in MACE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. These landmark findings have important implications for clinicians -as they mean that weight loss and/or semaglutide as anti-obesity pharmacotherapy could be a treatment strategy for secondary prevention of CV disease in patients with overweight or obesity. It is, however, unknown whether weight loss with either calorie-restricted diet or semaglutide has beneficial effects in obese subjects with heart failure and reduced ejection fraction. Also it is unclear whether semaglutide has cardiovascular benefits irrespective of starting weight and amount of weight loss. Purpose: The study aims to investigate whether weight loss treatment with semaglutide is superior to weight loss with calorie-restricted diet in improving peak oxygen uptake in patients with obesity and heart failure with reduced ejection fraction.

Deep Learning Detection of Pulmonary Hypertension and Low Ejection Fraction Via Digital Stethoscope and 3-Lead ECG

This is a prospective, observational study evaluating whether heart sounds (phonocardiograms) and three-lead electrocardiograms (ECGs) recorded using the Eko CORE 500 digital stethoscope can help detect pulmonary hypertension (PH) and low left ventricular ejection fraction (EF ≤ 40%). PH is a condition characterized by high blood pressure in the pulmonary arteries, which can lead to heart failure and carries significant risks if undiagnosed. Low EF, which indicates reduced pumping ability of the heart, is also associated with increased risk of severe cardiac events but can remain undetected because patients often have no symptoms or only nonspecific symptoms. In this study, adults undergoing clinically indicated echocardiograms or right heart catheterization at outpatient sites will be invited to participate. Participants will complete a single study session lasting about 20 minutes, during which heart sounds and a three-lead ECG will be collected using the Eko CORE 500 device. If participants have had a clinical 12-lead ECG within 30 days of their echocardiogram or right heart catheterization, those data may also be used for analysis. A clinically indicated echocardiogram or right heart catheterization (RHC) performed within seven days before or after the Eko CORE 500 recording will serve as the reference standard to confirm the presence or absence of PH and low EF. Up to 3,850 participants may be enrolled across multiple sites to ensure that approximately 3,500 complete the study. The data collected will be used to develop and validate artificial intelligence (AI) algorithms that aim to detect PH and identify low EF, potentially enabling earlier and simpler screening for these conditions in clinical practice.

PCI With GDMT Versus GDMT Alone for Patients With Ischemic Cardiomyopathy and Reduced LVEF

To evaluate whether percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES) combined with guideline-directed medical therapy (GDMT), compared to GDMT alone, reduces the time to first occurrence of major adverse cardiovascular events (MACE) during a median follow-up of at least 24 months, measured at the time the last enrolled patient reaches 12 months, in patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤40%. MACE is a composite of cardiovascular \[CV\] death, myocardial infarction (MI), heart failure (HF) related rehospitalization, heart transplantation, requirement for durable left ventricular assist device \[LVAD\] implantation, or worsening heart failure treated as an out-patient requiring treatment with intravenous medications.

Assessment of Combined CCM and ICD Device in HFrEF

The goal of this clinical trial is to demonstrate that the OPTIMIZER® Integra CCM-D System (the "CCM-D System") can safely and effective convert induced ventricular fibrillation (VF) and spontaneous ventricular tachycardia and/or ventricular fibrillation (VT/VF) episodes in subjects with Stage C or D heart failure who remain symptomatic despite being on guideline-directed medical therapy (GDMT), are not indicated for cardiac resynchronization therapy (CRT), and have heart failure with reduced left ventricular ejection fraction (LVEF ≤40%). Eligible subjects will be implanted with the CCM-D System. A subset of subjects will be induced into ventricular fibrillation "on the table" in the implant procedure room. During the follow-up period, inappropriate shock rate and device-related complications will be evaluated. The follow-up period is expected to last at least two years.

An Early Feasibility Study Evaluation of an Implant Free Interatrial Shunt to Improve Heart Failure

The purpose of this early feasibility study is to evaluate the safety and feasibility of the device for percutaneous shunting of the interatrial septum and improvement of heart failure related symptoms. The primary goal is to determine if the device is safe to use. The findings from this study may be used to refine the intended patient population, the design of the device, or develop a subsequent randomized study.

STRATegy SUccesS in High-Risk PCI With Impella CP: Evaluation of Hemodynamic Protection in Complex PCI

STRATUS-PCI is a pilot clinical trial that compares two ways of running a small heart pump called Impella CP during a high-risk procedure to open blocked heart arteries (percutaneous coronary intervention, or PCI) in patients with weakened heart muscle. The pump is placed temporarily through an artery in the leg and sits across the aortic valve to help maintain blood flow during the procedure. Fifty patients will be randomly assigned in equal numbers to one of two pump settings: an automatic mode that adjusts flow up to higher levels as needed, or a fixed lower-flow mode (P-2). The doctor performing the heart procedure will not know which setting is being used (double-blind). A separate doctor monitors blood pressure and is allowed to change the pump setting at any time if the patient becomes unstable. The main question is whether the automatic mode helps doctors complete the planned heart procedure more successfully and without drops in blood pressure or other complications. Results will help design a larger future trial.

High Fat Diet for Cardiac Metabolic Reprogramming

Heart failure (HF) continues to be a leading cause of morbidity and mortality worldwide, despite advances in treatment. HF is often characterized by an altered metabolism in the heart, where glucose is favored over fatty acids as the primary energy substrate. This metabolic shift has been hypothesized to contribute to disease progression. Previous studies using animal models have demonstrated that restoring fatty acid metabolism through dietary intervention can reverse the adverse metabolic effects and improve heart function. A transgenic murine model with mitochondrial defects, for instance, exhibited improved cardiac function after an HFD intervention. These findings were reinforced by a translational pig model of non-ischemic DCM, where a high-fat diet significantly improved LVEF compared to a standard diet. Building upon these promising preclinical results, a small-scale human study showed that lipid infusion, rather than glucose, improved cardiac function in HF patients. However, the long-term benefits of a HFD in heart failure patients have yet to be thoroughly explored. The HF4HF trial aims to fill this gap by evaluating the effects of an HFD over a two-month period in patients with non-ischemic DCM and reduced LVEF. The "High Fat Diet for Heart Failure" (HF4HF) study is a proof-of-concept randomized controlled trial designed to investigate the efficacy of a high-fat diet (HFD) as a therapeutic intervention in patients with non-ischemic dilated cardiomyopathy (DCM) and reduced left ventricular ejection fraction (LVEF). The study hypothesizes that cardiac metabolic reprogramming, achieved through a controlled nutritional intervention involving an HFD, can enhance systolic function, myocardial energetics, and overall heart function in heart failure (HF) patients. Cofunded by the European Commission and national entities, the trial is spearheaded by a consortium of cardiovascular research centers across four countries: Spain, Italy, France, and Romania.

Study of JK07 in Patients With Chronic Heart Failure

This is a Phase 2, randomized, double-blind, placebo-controlled, multiple dose study to assess the safety, tolerability, and efficacy of JK07 in participants aged 18-85 with heart failure. There will be 2 cohorts in this study: Cohort 1: Heart failure (HF) participants with left ventricular ejection fraction (LVEF) of ≤ 40%. Cohort 2: Heart failure (HF) participants with left ventricular ejection fraction (LVEF) \> 40% and ≤ 65%.

Dietary Intervention and Physical Activity in Patients With Heart Failure and Reduced Ejection Fraction

Heart failure with reduced ejection fraction (HFrEF) is frequently associated with abnormalities in body composition, including reduced skeletal muscle mass and sarcopenia, which are independent predictors of reduced exercise tolerance, impaired quality of life, and increased mortality. Despite advances in pharmacological therapy, evidence-based non-pharmacological strategies aimed at preventing muscle mass loss remain limited. This randomized controlled trial aims to evaluate the effects of dietary intervention based on the DASH diet with high-protein elements, resistance exercise training, and their combination on skeletal muscle mass, functional capacity, echocardiographic parameters, biochemical markers, and quality of life in patients with HFrEF.

HFrEF Polypill in Sri Lanka RCT

Primary Outcome: Composite of cardiovascular death or recurrent heart failure hospitalization over study duration Secondary Outcomes: Cardiovascular death over study duration Recurrent heart failure hospitalizations over study duration All-cause mortality over study duration Change in left ventricular ejection fraction from baseline to 12 months by echocardiogram. Change in natriuretic peptide levels from baseline to 12 months. Change in health-related quality of life from baseline to 12 months using the Kansas City Cardiomyopathy Questionnaire. Change in New York Heart Association functional class from baseline to 12 months. Adherence to heart failure medications assessed by pill count and questionnaire, medication persistence assessed as continuation of assigned therapy after initiation, and dose optimization assessed as proportion achieving final/target doses over study duration Safety Outcomes: Proportion of participants with serious adverse events or sudden unexpected serious adverse reaction over study duration Proportion with adverse events of special interest (symptomatic hypotension, diabetic ketoacidosis, severe hypoglycemia, lower limb amputation, hyperkalemia, or worsening kidney function) over study duration Proportion of participants who stop study drug because of adverse events over study duration Change in serum potassium over study duration Change in serum creatinine over study duration Participants will be randomly assigned to one of two groups, intervention or usual care. The intervention group will be given four guideline-recommended medications for heart failure with reduced ejection fraction, combined in one over-encapsulated pill, with three dose strength options (at the discretion of their treating physician). Both groups will be observed over a minimum of 12-months of follow-up to assess their medication adherence, clinical symptoms, laboratory measures, health related quality of life, and need for medication adjustment amongst other measures.

Comparative Effectiveness of Prophylactic ICD Versus Non-ICD Therapy

The investigators aim to compare the risk of mortality of Non-implantable carioverter defibrillator (ICD) vs. ICD management in patients with heart failure with reduced ejection fraction (HFrEF).

Ketones in Heart Failure With Reduced Ejection Fraction

The purpose of this study is to understand the effects of a ketone drink on exercise capacity and other cardiovascular parameters in patients with heart failure. In heart failure, patients are limited in their ability to do all the things they want to do, and exercise as much as they would like, due to becoming tired and short of breath early. There may be several reasons why these symptoms occur. This study is assessing whether the ketone drink can improve these symptoms. This drink has been given status by Food and Drug Administration as "generally regarded as safe". The use of DeltaG in this study is experimental. DeltaG has not been approved by the Food and Drug Administration (FDA) for the use being evaluated in this study.

Pilot Study Lp299v Supplementation in Chronic Heart Failure

The goal of this study is to determine the impact of 12 weeks of Lp299v supplementation (20 million cfu/day vs. placebo) on exercise capacity, circulating biomarkers of cardiac remodeling, quality of life, and vascular endothelial function in humans with heart failure and reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) who have evidence of residual inflammation based on an elevated C-reactive protein level. This will be done in the setting of a randomized, double-blind, placebo-controlled trial.