Heart Failure, Systolic Clinical Trial
Official title:
Pulse Reduction On Beta-blocker and Ivabradine Therapy
Heart failure with reduced left ventricular ejection fraction (HFrEF) is the most common form of chronic heart failure in subjects ≤ 75 years of age. Beta-blocker therapy greatly reduces mortality and improves ventricular function in HFrEF patients, but 30-40% of patients do not show improvement in ventricular function with beta blockade. An extensive gene signaling network downstream from the beta1-adrenergic receptor, the primary target of beta-blocker therapy is likely important for development and progression HFrEF. Pathologic changes in this gene signaling network are only reversed towards normal levels when ventricular function improves. One potential mechanism for failure to improve ventricular function in HFrEF patients unresponsive to beta blocker therapy is a lack of heart rate reduction. Ivabradine is an FDA-approved medication believed to have therapeutic benefit in HFrEF patients through reduction in heart rate independent of beta-blockade. Ivabradine has been shown to reduce the risk of hospitalization for worsening HF in patients with stable, symptomatic chronic heart failure with reduced EF (≤ 35%)in sinus rhythm with resting heart rate ≥ 70 bpm and who are on maximally tolerated doses of beta blockers or who have a contraindication to beta blockers. Given the high rate of mortality and hospitalization of HFrEF patients even with current therapies, there is a large unmet need for improving HFrEF therapy. The goals of this study are to test the hypothesis that heart rate reduction is an important antecedent for improvement in ventricular function, and to identify components of the beta1-adrenergic receptor gene signaling network responsible for improvement in ventricular function caused by heart rate reduction.
The Pulse Reduction on Beta-blocker and Ivabradine Therapy (PROBE-IT) Study is a double-blind, randomized, two-arm parallel group, placebo-controlled design that compares the effect of heart rate reduction on ventricular reverse remodeling (assessed by LVEF change at 24 weeks) and on the beta1-gene signaling network in NYHA Class I-III HFrEF patients with an idiopathic dilated cardiomyopathy etiology (HFrEF/IDC), who are in sinus rhythm and whose heart rates remain ≥ 70 bpm on target or maximally tolerated doses of beta-blockers to which they have evidence of non-response by LVEF (< 5 absolute percentage points). Eligible patients will be randomized (2:1) to blinded treatment with ivabradine or matching placebo and will be initiated as per Corlanor® prescribing information over 4 weeks. The dose at 4 weeks post randomization will be considered the intention-to-treat end of titration dose, but further dose adjustment can be made based on clinical factors. The primary endpoint, i.e., effect of heart rate reduction on reverse remodeling (LVEF), will be assessed after 24 weeks. LV phenotyping by 3D-echocardiography, endomyocardial biopsy and coronary sinus sampling for cardiac norepinephrine levels will be performed at baseline and at 24 weeks. Exercise testing at baseline will be performed to assess level of beta blockade. Upon completion of the study, gene expression in endomyocardial biopsy tissue samples for each patient will be quantified using RNA-seq and quantified with respect to phenotypic measurements including LVEF and heart rate changes. After the Week 24 Visit, patients will return for an End-of-Study Visit and be offered open label ivabradine with dose initiation accomplished by stopping study drug and starting Corlanor at 5 mg BID or 2.5 mg BID if the patient is taking that dose of study drug. Investigators and patients will not be informed of the blinded study drug assignment at the time of study completion. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Withdrawn |
NCT03227393 -
The Effect of Yoga on Cardiac Sympathetic Innervation Evaluated by I-123 mIBG
|
N/A | |
Recruiting |
NCT04528004 -
Mechanistic Studies of Nicotinamide Riboside in Human Heart Failure
|
Early Phase 1 | |
Recruiting |
NCT04703842 -
Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction
|
Phase 1/Phase 2 | |
Recruiting |
NCT04522609 -
Electrostimulation of Skeletal Muscles in Patients Listed for a Heart Transplant
|
N/A | |
Completed |
NCT05475028 -
Network Medicine Approaches to Classify Heart Failure With PReserved Ejection Fraction by Signatures of DNA Methylation and Point-of-carE Risk calculaTors (PRESMET)
|
||
Not yet recruiting |
NCT05988749 -
Digital Remote Home Monitoring for Heart Failure
|
N/A | |
Not yet recruiting |
NCT06240403 -
Digoxin and Senolysis in Heart Failure and Diabetes Mellitus
|
Phase 2 | |
Recruiting |
NCT04950218 -
The Psoriasis Echo Study
|
||
Suspended |
NCT04701112 -
Acute Hemodynamic Effects of Pacing the His Bundle in Heart Failure
|
N/A | |
Completed |
NCT03305692 -
ECG Belt vs. Echocardiographic Optimization of CRT
|
N/A | |
Recruiting |
NCT05933083 -
MCNAIR Study: coMparative effeCtiveness of iN-person and teleheAlth cardIac Rehabilitation
|
N/A | |
Enrolling by invitation |
NCT03903107 -
The Fluoroless-CSP Trial Using Electroanatomic Mapping
|
N/A | |
Withdrawn |
NCT04872959 -
TRANSFORM Heart Failure With Reduced Ejection Fraction
|
N/A | |
Completed |
NCT02920918 -
Treatment of Diabetes in Patients With Systolic Heart Failure
|
Phase 4 | |
Completed |
NCT02334891 -
Kyoto Congestive Heart Failure Study
|
||
Recruiting |
NCT03553303 -
Pharmacodynamic Effects of Sacubitril/Valsartan on Natriuretic Peptides, Angiotensin and Neprilysin
|
Phase 4 | |
Recruiting |
NCT04083690 -
Multi-lead ECG to Effectively Optimize Resynchronization Devices: New CRT Recipients
|
N/A | |
Recruiting |
NCT03830957 -
Efficacy and Safety of Ivabradine to Reduce Heart Rate Prior to Coronary CT-angiography in Advanced Heart Failure: Comparison With β-Blocker
|
N/A | |
Recruiting |
NCT06121323 -
Physiological Effects of Lactate in Individuals With Chronic Heart Failure
|
N/A | |
Completed |
NCT03351283 -
Effect of Sodium Intake on Brain Natriuretic Peptide Levels in Patients With Heart Failure
|
N/A |