CLINICAL TRIALS PROFILE FOR IVABRADINE HYDROCHLORIDE

All Clinical Trials for Ivabradine Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00143507 ↗	The BEAUTIFUL Study: Effects of Ivabradine in Patients With Stable Coronary Artery Disease and Left Ventricular Systolic Dysfunction	Completed	Institut de Recherches Internationales Servier	Phase 3	2004-12-01	The aim of this study is to test whether ivabradine is able to reduce cardiovascular events when given to patients with coronary artery disease and impaired heart function.
NCT00202566 ↗	Efficacy and Safety of Ivabradine on Top of Atenolol in Stable Angina Pectoris	Completed	Institut de Recherches Internationales Servier	Phase 3	2005-06-01	To test whether ivabradine when given in combination with atenolol is able to improve the exercise tolerance of patients with stable angina pectoris
NCT00202579 ↗	Efficacy and Safety of Ivabradine in Severe Congestive Heart Failure	Completed	Institut de Recherches Internationales Servier	Phase 2	2004-09-01	To evaluate the effects on heart function of ivabradine administered to patients with severe chronic heart failure
NCT00757055 ↗	If Channel Blockade With Ivabradine in Patients With Diastolic Heart Failure	Withdrawn	St Vincent's University Hospital, Ireland	Phase 2	2012-12-01	The purpose of this study is to investigate whether the medicine ivabradine, a novel drug which slows the heart rate has a favourable effect on patients with diastolic heart failure. Ivabradine is a specific heart rate-lowering agent. It has a licence for treating patients with angina who are intolerant of agents such as beta blockers or whose angina is not adequately controlled. It has been shown to prolong exercise tolerance in these patients and to reduce the frequency of chest pain. Its mechanism of action is felt to be purely due to reducing heart rate, by as much as 10 beats per minute at rest, as well as by reducing the heart rate response to exercise. Patients with diastolic heart failure often complain of breathlessness on exertion which relates to the stiffness or lack of compliance of their heart i.e. the heart fails to relax rapidly enough to allow it to fill with blood between each heart beat. This may result in high pressure in the heart chamber which backs up in to the lungs and may be experienced as breathlessness. There is little evidence that any specific therapy benefits patients with this type of heart failure besides treating coexisting problems such as high blood pressure or angina. By slowing the heart rate down with ivabradine, the heart would have a longer time to fill during exercise which would make it more effective. This slowing of the heart rate may therefore relieve the breathlessness experienced on activity such as walking to the shops or up a flight of stairs etc.
NCT00815100 ↗	Effects of the Ivabradine on Reduction of Inflammatory Markers in Patients With Acute Coronary Syndrome	Completed	Hospital Universitario de Canarias	Phase 4	2009-04-01	The purpose of this study is to investigate whether a pure heart rate-lowering agent (Ivabradine) reduces vascular inflammatory stress in patients with acute coronary syndromes
NCT00825123 ↗	Effects of Heart Rate Reduction on Central Arterial Pressure in Healthy Individuals	Terminated	Baker Heart and Diabetes Institute	Phase 4	2008-10-01	The purpose of this project is to determine the effects of slowing heart rate upon both central and peripheral blood pressures using Ivabradine. The effects of Ivabradine will be compared to Metoprolol and placebo. Participants will attend the hospital for 3 visits where they will be randomised to receive either Ivabradine, Metoprolol and placebo on each visit. Non-invasive measures of blood pressure will be recorded before and after consuming the study drug.
NCT00825123 ↗	Effects of Heart Rate Reduction on Central Arterial Pressure in Healthy Individuals	Terminated	Bayside Health	Phase 4	2008-10-01	The purpose of this project is to determine the effects of slowing heart rate upon both central and peripheral blood pressures using Ivabradine. The effects of Ivabradine will be compared to Metoprolol and placebo. Participants will attend the hospital for 3 visits where they will be randomised to receive either Ivabradine, Metoprolol and placebo on each visit. Non-invasive measures of blood pressure will be recorded before and after consuming the study drug.

Clinical Trial Conditions for Ivabradine Hydrochloride

Condition Name

Condition Name for Ivabradine Hydrochloride
Intervention	Trials
Heart Failure	14
Coronary Artery Disease	6
Atrial Fibrillation	5
Cardiogenic Shock	3

Condition MeSH

Condition MeSH for Ivabradine Hydrochloride
Intervention	Trials
Heart Failure	32
Myocardial Ischemia	13
Coronary Artery Disease	12
Coronary Disease	9

Clinical Trial Locations for Ivabradine Hydrochloride

Trials by Country

Trials by Country for Ivabradine Hydrochloride
Location	Trials
United States	24
China	13
Italy	11
Egypt	7
United Kingdom	6

Trials by US State

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

Clinical Trial Progress for Ivabradine Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Ivabradine Hydrochloride
Clinical Trial Phase	Trials
Phase 4	35
Phase 3	17
Phase 2/Phase 3	2

Clinical Trial Status

Clinical Trial Status for Ivabradine Hydrochloride
Clinical Trial Phase	Trials
Completed	28
Unknown status	21
Recruiting	17

Clinical Trial Sponsors for Ivabradine Hydrochloride

Sponsor Name

Sponsor Name for Ivabradine Hydrochloride
Sponsor	Trials
Amgen	6
Institut de Recherches Internationales Servier	6
Servier	3

Sponsor Type

Sponsor Type for Ivabradine Hydrochloride
Sponsor	Trials
Other	109
Industry	11
U.S. Fed	1

Ivabradine Hydrochloride: Clinical Trials, Market Analysis, and Projections

Clinical Trials and Efficacy of Ivabradine Hydrochloride

Background and Mechanism

Ivabradine hydrochloride is a heart rate reducer that works by inhibiting the hyperpolarization-activated sodium channel (I_f) in the sinoatrial node, thereby reducing the heart rate without affecting blood pressure, ventricular repolarization, or myocardial contractility[4].

Key Clinical Trials

Several clinical trials have been conducted to evaluate the efficacy and safety of ivabradine in patients with heart failure and other cardiovascular conditions.

SHIFT Trial

The SHIFT (Systolic Heart Failure Treatment with the I_f Inhibitor Ivabradine Trial) is one of the most significant trials. It demonstrated that ivabradine, when added to standard therapy, significantly reduced the composite endpoint of cardiovascular death or hospitalization for worsening heart failure in patients with heart failure with reduced ejection fraction (HFrEF) and a heart rate ≥70 beats per minute. The trial showed a 18% reduction in the primary composite endpoint, with a significant reduction in hospitalizations for worsening heart failure and non-fatal myocardial infarction[1][3].

BEAUTIFUL Trial

The BEAUTIFUL (MorBidity-Mortality Evaluation of the I_f Inhibitor Ivabradine in Patients with Coronary Artery Disease and Left Ventricular Dysfunction) trial, although neutral in its primary outcome, provided insights into the potential benefits of ivabradine in patients with coronary artery disease and left ventricular dysfunction. It showed a reduction in hospitalization for myocardial infarction and coronary revascularization in patients with heart rates ≥70 beats per minute[4].

J-SHIFT and PRIME-HF Trials

Other trials like J-SHIFT and PRIME-HF have also supported the efficacy of ivabradine in reducing heart rate and improving outcomes in patients with heart failure. These trials have shown significant reductions in heart rate and composite endpoints such as cardiovascular death or hospitalization for worsening heart failure[1].

Safety and Adverse Events

While ivabradine has shown significant benefits, it is not without adverse effects. Common adverse events include symptomatic and asymptomatic bradycardia, atrial fibrillation, phosphenes (a visual disturbance), and blurred vision. The SHIFT trial noted an increased incidence of atrial fibrillation in the ivabradine group compared to the placebo group, which is a significant concern[3][4].

Market Analysis and Projections

Current Market Size and Growth

The global ivabradine hydrochloride market has experienced rapid growth in recent years. As of 2023, the market size was valued in billions of USD, and it is anticipated to continue growing substantially until 2031. This growth is driven by increasing demand for heart rate reduction therapies, especially in the context of heart failure and coronary artery disease[2][5].

Market Segmentation

The market is segmented based on type (5mg/tablet and 7.5mg/tablet), application (hospitals, retail pharmacies, clinics, and others), and geographical regions (North America, Europe, Asia-Pacific, South America, and the Middle East & Africa). This segmentation helps in understanding the diverse market dynamics and identifying key growth areas[2][5].

Key Players

Prominent companies in the ivabradine hydrochloride market include Les Laboratoires Servier, Shandong New Time Pharmaceutical Co. Ltd., Chongqing Southwest NO.2 Pharmaceutical Factory Co. Ltd., Beijing Baiao Pharmaceuticals Co. Ltd., and Cadiasun Pharma GmbH. These companies play a crucial role in manufacturing and distributing ivabradine hydrochloride globally[2].

Market Drivers and Challenges

The market growth is driven by factors such as the increasing prevalence of heart failure and coronary artery disease, the efficacy of ivabradine in reducing heart rate and improving outcomes, and the expanding approval of ivabradine for various indications. However, challenges include the potential for adverse events like atrial fibrillation, the need for careful patient selection, and the competition from other heart rate reduction therapies[2][3].

Market Outlook

The market outlook for ivabradine hydrochloride is positive, with projections indicating robust growth rates over the forecast period from 2024 to 2031. The analysis involves a thorough exploration of Porter's 5 Forces Framework, macroeconomic evaluation, scrutiny of the value chain, and a comprehensive pricing analysis. These factors collectively shape the current market dynamics and are expected to continue influencing the market in the future[2].

Real-World Evidence and Observational Studies

Importance of Real-World Evidence

In addition to randomized controlled trials (RCTs), real-world evidence (RWE) from observational studies has become increasingly important. These studies provide insights into the effectiveness and safety of ivabradine in routine clinical practice, which can complement the findings from RCTs. Observational studies have shown that ivabradine can significantly reduce the risk of cardiovascular death and all-cause hospitalizations when used on top of background therapy[1].

Observational Study Findings

Studies by Liao et al. and Guzman et al. have reported significant reductions in cardiovascular death and all-cause hospitalizations with the use of ivabradine in real-world settings. These findings align with the RCT data and support the broader applicability of ivabradine in clinical practice[1].

Regulatory Considerations

FDA and EMA Approvals

Ivabradine has received approvals from regulatory bodies such as the FDA and EMA for specific indications. The EMA has extended ivabradine’s approval to allow its use in combination with beta-blockers, provided heart rates remain above 60 beats per minute[4].

Labeling and Drug-Drug Interactions

The FDA has emphasized the need for precise labeling regarding drug-drug interactions, especially with CYP3A4 inducers. This is crucial for ensuring safe and effective use of ivabradine in clinical practice[3].

Conclusion

Ivabradine hydrochloride has established itself as a valuable therapy for reducing heart rate and improving outcomes in patients with heart failure and other cardiovascular conditions. The clinical trials, particularly the SHIFT and BEAUTIFUL trials, have provided strong evidence of its efficacy. The market for ivabradine hydrochloride is expected to grow significantly, driven by increasing demand and expanding approvals.

Key Takeaways

• Efficacy in Heart Failure: Ivabradine significantly reduces the risk of hospitalization for worsening heart failure and cardiovascular death in patients with HFrEF.
• Adverse Events: Common adverse events include bradycardia, atrial fibrillation, and visual disturbances.
• Market Growth: The global ivabradine hydrochloride market is projected to grow substantially until 2031.
• Real-World Evidence: Observational studies support the effectiveness and safety of ivabradine in routine clinical practice.
• Regulatory Approvals: Ivabradine has received approvals from FDA and EMA for specific indications.

FAQs

What is the primary mechanism of action of ivabradine hydrochloride?

Ivabradine hydrochloride works by inhibiting the hyperpolarization-activated sodium channel (I_f) in the sinoatrial node, thereby reducing the heart rate.

Which clinical trials have been most significant in evaluating ivabradine hydrochloride?

The SHIFT and BEAUTIFUL trials are the most significant, demonstrating ivabradine's efficacy in reducing heart rate and improving outcomes in patients with heart failure and coronary artery disease.

What are the common adverse events associated with ivabradine hydrochloride?

Common adverse events include symptomatic and asymptomatic bradycardia, atrial fibrillation, phosphenes, and blurred vision.

How is the global ivabradine hydrochloride market segmented?

The market is segmented based on type (5mg/tablet and 7.5mg/tablet), application (hospitals, retail pharmacies, clinics, and others), and geographical regions.

What is the projected growth of the ivabradine hydrochloride market until 2031?

The market is anticipated to grow substantially, driven by increasing demand and expanding approvals, with robust growth rates expected over the forecast period.

Sources

1. Ivabradine in patients with heart failure: a systematic literature review - Tandfonline
2. Ivabradine Hydrochloride Market Size, Scope And Forecast Report - Market Research Intellect
3. 206143Orig1s000 - accessdata.fda.gov - FDA
4. The Clinical Use of Ivabradine - JACC Journals
5. Global Ivabradine Hydrochloride Market 2024 by Manufacturers, Regions, Type and Application, Forecast to 2030 - Market Research Reports