CLINICAL TRIALS PROFILE FOR CORLANOR

All Clinical Trials for Corlanor

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02827500 ↗	Predischarge Initiation of Ivabradine in the Management of Heart Failure (PRIME-HF)	Completed	Amgen	Phase 4	2016-07-01	The PRIME-HF study is a multi-center, patient-level, randomized, open-label study of approximately 450 patients with reduced (left ventricular ejection fraction) LVEF of ≤ 35% and heart-rate ≥70 beats per minute (bpm) who are being discharged from the hospital following stabilization from acute heart failure (HF)(primary or secondary) and will be randomized to a treatment strategy of predischarge initiation of ivabradine or usual care. All participants should have a follow-up visit within 7-14 days of hospital discharge. Heart rate and systolic blood pressure will be assessed at this clinical visit. For participants randomized to predischarge initiation of ivabradine and on ivabradine 5mg BID, the heart rate may be used to adjust the dose the dose to 2.5mg BID or 7.5mg BID. For participants randomized to usual care, ivabradine may be initiated at the provider's discretion. All participants will have a second follow-up study visit 6 weeks (42 +/- 14 days) post-discharge. Heart rate, systolic blood pressure and quality of life (KCCQ and PGA) will be assessed. For participants already taking ivabradine in either treatment group, the heart rate may again be used to adjust the dose of ivabradine. For participants not yet receiving ivabradine, it may be initiated at the provider's discretion. All participants will receive a 90 (+/-7) day post-discharge phone call by site to assess for event status and tolerability of ivabradine. All participants will have a final study visit at 180 (+/-14) days post-discharge. Heart rate, systolic blood pressure and quality of life (Kansas City Cardiomyopathy Questionnaire and Patient Global Assessment) will be assessed. The attending physician may initiate ivabradine per usual care clinical practice. The primary hypothesis of the PRIME-HF study is that, compared with usual care, a treatment strategy of initiation of ivabradine prior to discharge for a hospitalization with acute HF will be associated with a greater proportion of participants using ivabradine at 180 days. Secondary objectives are to assess the impact of predischarge initiation of ivabradine on:Heart Rate (Change in heart rate from baseline to 180 days and Median heart rate at 180 days) and Patient-Centered Outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and Patient Global Assessment (PGA)). Tertiary objectives will be to explore the impact of predischarge initiation of ivabradine on other assessments of evidence-based implementation of ivabradine and beta-blockers at 180 days. Evaluations will incorporate data based on whether or not indication status was retained and whether or not an ivabradine prescription was provided. Tolerability of ivabradine and adverse events during study follow-up.
NCT02827500 ↗	Predischarge Initiation of Ivabradine in the Management of Heart Failure (PRIME-HF)	Completed	Duke University	Phase 4	2016-07-01	The PRIME-HF study is a multi-center, patient-level, randomized, open-label study of approximately 450 patients with reduced (left ventricular ejection fraction) LVEF of ≤ 35% and heart-rate ≥70 beats per minute (bpm) who are being discharged from the hospital following stabilization from acute heart failure (HF)(primary or secondary) and will be randomized to a treatment strategy of predischarge initiation of ivabradine or usual care. All participants should have a follow-up visit within 7-14 days of hospital discharge. Heart rate and systolic blood pressure will be assessed at this clinical visit. For participants randomized to predischarge initiation of ivabradine and on ivabradine 5mg BID, the heart rate may be used to adjust the dose the dose to 2.5mg BID or 7.5mg BID. For participants randomized to usual care, ivabradine may be initiated at the provider's discretion. All participants will have a second follow-up study visit 6 weeks (42 +/- 14 days) post-discharge. Heart rate, systolic blood pressure and quality of life (KCCQ and PGA) will be assessed. For participants already taking ivabradine in either treatment group, the heart rate may again be used to adjust the dose of ivabradine. For participants not yet receiving ivabradine, it may be initiated at the provider's discretion. All participants will receive a 90 (+/-7) day post-discharge phone call by site to assess for event status and tolerability of ivabradine. All participants will have a final study visit at 180 (+/-14) days post-discharge. Heart rate, systolic blood pressure and quality of life (Kansas City Cardiomyopathy Questionnaire and Patient Global Assessment) will be assessed. The attending physician may initiate ivabradine per usual care clinical practice. The primary hypothesis of the PRIME-HF study is that, compared with usual care, a treatment strategy of initiation of ivabradine prior to discharge for a hospitalization with acute HF will be associated with a greater proportion of participants using ivabradine at 180 days. Secondary objectives are to assess the impact of predischarge initiation of ivabradine on:Heart Rate (Change in heart rate from baseline to 180 days and Median heart rate at 180 days) and Patient-Centered Outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and Patient Global Assessment (PGA)). Tertiary objectives will be to explore the impact of predischarge initiation of ivabradine on other assessments of evidence-based implementation of ivabradine and beta-blockers at 180 days. Evaluations will incorporate data based on whether or not indication status was retained and whether or not an ivabradine prescription was provided. Tolerability of ivabradine and adverse events during study follow-up.
NCT02973594 ↗	Pulse Reduction On Beta-blocker and Ivabradine Therapy	Recruiting	American Heart Association	Phase 4	2016-11-01	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.
NCT02973594 ↗	Pulse Reduction On Beta-blocker and Ivabradine Therapy	Recruiting	Ohio State University	Phase 4	2016-11-01	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.
NCT02973594 ↗	Pulse Reduction On Beta-blocker and Ivabradine Therapy	Recruiting	University of Utah	Phase 4	2016-11-01	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.
NCT02973594 ↗	Pulse Reduction On Beta-blocker and Ivabradine Therapy	Recruiting	University of Colorado, Denver	Phase 4	2016-11-01	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.

Clinical Trial Conditions for Corlanor

Condition Name

Condition Name for Corlanor
Intervention	Trials
Heart Failure	3
Heart Transplantation, Elevated Resting Heart Rate	1
Tachycardia	1
Ventricular Remodeling	1

Condition MeSH

Condition MeSH for Corlanor
Intervention	Trials
Heart Failure	5
Ventricular Remodeling	1
Heart Failure, Systolic	1
Cardiomyopathy, Dilated	1

Clinical Trial Locations for Corlanor

Trials by Country

Trials by Country for Corlanor
Location	Trials
United States	22

Trials by US State

Trials by US State for Corlanor
Location	Trials
Michigan	3
Ohio	2
New York	2
Illinois	2
Colorado	2

Clinical Trial Progress for Corlanor

Clinical Trial Phase

Clinical Trial Phase for Corlanor
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	1

Clinical Trial Status

Clinical Trial Status for Corlanor
Clinical Trial Phase	Trials
Completed	2
Unknown status	2
Withdrawn	1

Clinical Trial Sponsors for Corlanor

Sponsor Name

Sponsor Name for Corlanor
Sponsor	Trials
Amgen	5
Duke University	1
American Heart Association	1

Sponsor Type

Sponsor Type for Corlanor
Sponsor	Trials
Other	7
Industry	6

Clinical Trials, Market Analysis, and Projections for Corlanor (Ivabradine)

Introduction to Corlanor

Corlanor, also known as ivabradine, is a medication approved by the FDA in 2015 to reduce the risk of hospitalization for worsening heart failure in patients with chronic heart failure. Here, we will delve into the clinical trials that led to its approval, its market analysis, and projections for its future impact.

Clinical Trials Overview

The approval of Corlanor was based on extensive global clinical trial data, particularly the Phase 3 SHIFT (Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial) study. Here are the key points from these trials:

Study Design

• The SHIFT study was a large, multicenter, randomized, double-blind, placebo-controlled trial conducted at 667 sites in 38 countries across Europe, Asia, Australia, and South America[4].
• Patients were randomly assigned to receive either Corlanor or a placebo, with neither the patients nor the healthcare professionals aware of the assignments until the trial was complete[4].

Patient Demographics

• The trial enrolled 6,505 patients with stable New York Heart Association class II to IV heart failure, left ventricular ejection fraction ≤ 35%, and resting heart rate ≥ 70 beats per minute (bpm)[4].
• Patients had to have been clinically stable for at least 4 weeks on an optimized clinical regimen that included maximally tolerated doses of beta-blockers, ACE inhibitors or Angiotensin Receptor Blockers, and spironolactone or other diuretics[4].

Primary Endpoints

• The primary composite endpoint was hospitalization for worsening heart failure or cardiovascular death. The study showed that Corlanor significantly reduced the risk of this endpoint, with an 18% relative risk reduction (RRR) and a 4.2% absolute risk reduction (ARR) compared to placebo[1].

Subgroup Analysis

• Subgroup analyses indicated that Corlanor was similarly effective in men and women, as well as in whites and Asians. However, due to the limited number of Black patients in the trial, differences in response for this group could not be determined. The drug was also effective across various age groups[4].

Adverse Reactions

• Common adverse drug reactions included bradycardia (10% vs. 2.2% for placebo), hypertension or increased blood pressure (8.9% vs. 7.8%), atrial fibrillation (8.3% vs. 6.6%), and luminous phenomena or visual brightness (2.8% vs. 0.5%)[1].

Mechanism of Action

Corlanor works by selectively inhibiting the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker, which regulates heart rate. This inhibition reduces the spontaneous pacemaker activity of the cardiac sinus node, thereby slowing the heart rate without affecting ventricular repolarization or myocardial contractility[1].

Market Analysis

Current Market

• The approval of Corlanor marked a significant advancement in the treatment of chronic heart failure. It has been incorporated into updated treatment guidelines by the American College of Cardiology, American Heart Association, and Heart Failure Society of America[3].

Market Size and Projections

• The global chronic heart failure drugs market is expected to grow significantly, driven by the increasing prevalence of heart failure. By 2030, the prevalence of heart failure is projected to increase by 46% from 2012 estimates, and the cost of heart failure in the U.S. is expected to rise by almost 127%[1].
• Specifically, the market size for ivabradine tablets (Corlanor) was estimated to be $145.3 million for the 12 months ending September 2024, according to IQVIA[5].

Competitive Landscape

• Corlanor competes in a market that includes other heart failure medications such as Entresto (sacubitril/valsartan). While Corlanor has shown significant benefits, some experts note that the data supporting Entresto may be stronger in certain aspects[3].

Generic Competition

• Recently, Alembic received FDA approval for a generic version of Corlanor, which could impact the market dynamics and pricing of the drug. Generic competition often leads to increased accessibility and reduced costs for patients[5].

Projections and Future Impact

Increasing Prevalence and Cost

• The growing prevalence of heart failure and the associated increase in healthcare costs underscore the need for effective treatments like Corlanor. By 2030, the cost of heart failure in the U.S. is expected to be significantly higher, making cost-effective treatments crucial[1].

Integration into Guidelines

• The inclusion of Corlanor in updated heart failure treatment guidelines by major medical organizations indicates its acceptance and potential for widespread use. This integration is expected to drive its adoption in clinical practice[3].

Generic Availability

• The availability of a generic version of Corlanor is likely to increase its accessibility to a broader patient population, potentially expanding its market share and reducing the financial burden on patients and healthcare systems[5].

Key Takeaways

• Corlanor (ivabradine) is approved to reduce the risk of hospitalization for worsening heart failure in patients with chronic heart failure.
• The drug's efficacy was established through the Phase 3 SHIFT study, showing an 18% relative risk reduction in hospitalization or cardiovascular death.
• Corlanor works by selectively inhibiting the HCN channel to slow the heart rate.
• The global chronic heart failure drugs market is projected to grow significantly due to increasing prevalence and costs.
• Generic competition is expected to impact the market dynamics and pricing of Corlanor.

FAQs

Q: What is Corlanor used for?

A: Corlanor (ivabradine) is used to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure and reduced left ventricular ejection fraction.

Q: How does Corlanor work?

A: Corlanor works by selectively inhibiting the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel, which reduces the heart rate without affecting ventricular repolarization or myocardial contractility.

Q: What were the key findings of the SHIFT study?

A: The SHIFT study showed that Corlanor significantly reduced the risk of hospitalization for worsening heart failure or cardiovascular death, with an 18% relative risk reduction and a 4.2% absolute risk reduction compared to placebo.

Q: Is Corlanor effective across different demographics?

A: Subgroup analyses indicated that Corlanor was similarly effective in men and women, as well as in whites and Asians. However, the response in Black patients could not be determined due to limited data.

Q: What is the market size and projection for Corlanor?

A: The market size for ivabradine tablets (Corlanor) was estimated to be $145.3 million for the 12 months ending September 2024. The global chronic heart failure drugs market is expected to grow significantly due to increasing prevalence and costs.

Sources

1. FDA Approves Corlanor® (ivabradine) To Reduce The Risk Of Hospitalization For Worsening Heart Failure In Patients With Chronic Heart Failure. Amgen.
2. Chronic Heart Failure Drugs Market and Forecast 2024-2031. iHealthcareAnalyst.
3. Two new drugs added to heart failure guidelines. American Heart Association.
4. Drug Trials Snapshot: CORLANOR. FDA.
5. Alembic receives FDA nod for generic Corlanor. Drug Store News.