CLINICAL TRIALS PROFILE FOR ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE

All Clinical Trials for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01822808 ↗	Bi Treatment With Hydralazine/Nitrates Versus Placebo in Africans Admitted With Acute Heart Failure	Unknown status	Momentum Research, Inc.	Phase 3	2013-01-01	To investigate the effect of hydralazine isosorbide dinitrate on clinical outcomes, symptoms, cardiac parameters and functional status of African patients hospitalized with AHF and left ventricular dysfunction during 24 weeks of therapy. Administration of hydralazine/nitrates will be superior to placebo administration in reducing HF readmission or death, improving dyspnoea, reducing blood pressure and brain natriuretic peptide (BNP) in African patients admitted with AHF and left ventricular dysfunction.
NCT01822808 ↗	Bi Treatment With Hydralazine/Nitrates Versus Placebo in Africans Admitted With Acute Heart Failure	Unknown status	University of Cape Town	Phase 3	2013-01-01	To investigate the effect of hydralazine isosorbide dinitrate on clinical outcomes, symptoms, cardiac parameters and functional status of African patients hospitalized with AHF and left ventricular dysfunction during 24 weeks of therapy. Administration of hydralazine/nitrates will be superior to placebo administration in reducing HF readmission or death, improving dyspnoea, reducing blood pressure and brain natriuretic peptide (BNP) in African patients admitted with AHF and left ventricular dysfunction.
NCT01516346 ↗	Vasodilator Therapy for Heart Failure and Preserved Ejection Fraction	Completed	National Institute on Aging (NIA)	Phase 2	2012-01-01	The main objective is to test the effect of prolonged therapy (24 weeks) with isosorbide dinitrate ± hydralazine on arterial wave reflections (primary endpoint). Secondary endpoints include left ventricular (LV) mass, fibrosis and diastolic function) and exercise capacity (assessed via the 6-minute walk test) in patients with Heart Failure and Preserved Ejection Fraction (HFPEF). We will also test the hypothesis that the reduction in arterial wave reflections induced by vasoactive therapy will correlate with the improvement in exercise capacity, LV mass, fibrosis and diastolic function. Finally, we will assess whether the hemodynamic response to an acute dose of sublingual nitroglycerin (NTG) can predict the sustained changes in the reflected wave and other hemodynamic parameters in response to chronic vasodilator therapy.
NCT01516346 ↗	Vasodilator Therapy for Heart Failure and Preserved Ejection Fraction	Completed	University of Pennsylvania	Phase 2	2012-01-01	The main objective is to test the effect of prolonged therapy (24 weeks) with isosorbide dinitrate ± hydralazine on arterial wave reflections (primary endpoint). Secondary endpoints include left ventricular (LV) mass, fibrosis and diastolic function) and exercise capacity (assessed via the 6-minute walk test) in patients with Heart Failure and Preserved Ejection Fraction (HFPEF). We will also test the hypothesis that the reduction in arterial wave reflections induced by vasoactive therapy will correlate with the improvement in exercise capacity, LV mass, fibrosis and diastolic function. Finally, we will assess whether the hemodynamic response to an acute dose of sublingual nitroglycerin (NTG) can predict the sustained changes in the reflected wave and other hemodynamic parameters in response to chronic vasodilator therapy.
NCT01516346 ↗	Vasodilator Therapy for Heart Failure and Preserved Ejection Fraction	Completed	Corporal Michael J. Crescenz VA Medical Center	Phase 2	2012-01-01	The main objective is to test the effect of prolonged therapy (24 weeks) with isosorbide dinitrate ± hydralazine on arterial wave reflections (primary endpoint). Secondary endpoints include left ventricular (LV) mass, fibrosis and diastolic function) and exercise capacity (assessed via the 6-minute walk test) in patients with Heart Failure and Preserved Ejection Fraction (HFPEF). We will also test the hypothesis that the reduction in arterial wave reflections induced by vasoactive therapy will correlate with the improvement in exercise capacity, LV mass, fibrosis and diastolic function. Finally, we will assess whether the hemodynamic response to an acute dose of sublingual nitroglycerin (NTG) can predict the sustained changes in the reflected wave and other hemodynamic parameters in response to chronic vasodilator therapy.

Clinical Trial Conditions for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE

Condition Name

Condition Name for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Intervention	Trials
Heart Failure	4
Acute Heart Failure	1
Cardio-Renal Syndrome	1
Chronic Hemodialysis (ESRD)	1

Condition MeSH

Condition MeSH for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Intervention	Trials
Heart Failure	5
Kidney Failure, Chronic	1
Ventricular Dysfunction, Left	1
Ventricular Dysfunction	1

Clinical Trial Locations for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE

Trials by Country

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Trials by Country for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Location	Trials
United States	22
South Africa	1
Denmark	1
Singapore	1

Trials by US State

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−

Trials by US State for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Location	Trials
Georgia	2
Florida	2
Alabama	2
Massachusetts	2
Pennsylvania	2

Clinical Trial Progress for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Clinical Trial Phase	Trials
Phase 4	2
Phase 3	2
Phase 2	1

Clinical Trial Status

Clinical Trial Status for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	3
Unknown status	2
Active, not recruiting	1

Clinical Trial Sponsors for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE

Sponsor Name

Sponsor Name for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Sponsor	Trials
The Danish Regions: Foundation for Medical Research	1
Brigham and Women's Hospital	1
The Novo Nordisk Foundation	1

Sponsor Type

Sponsor Type for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Sponsor	Trials
Other	14
Industry	2
U.S. Fed	1

Isosorbide Dinitrate and Hydralazine Hydrochloride: Clinical Trials, Market Analysis, and Projections

Introduction

Isosorbide dinitrate and hydralazine hydrochloride, combined in the drug BiDil, have been a significant focus in the treatment of heart failure, particularly among African-American patients. This article delves into the clinical trials, market analysis, and future projections for this medication.

Clinical Trials Overview

The African-American Heart Failure Trial (A-HeFT)

The A-HeFT trial was a pivotal study that demonstrated the efficacy of the combination of isosorbide dinitrate and hydralazine hydrochloride in reducing mortality and hospitalization rates among African-American patients with heart failure. The trial involved 1,050 African-American patients with New York Heart Association (NYHA) class III or IV heart failure and showed a 43% reduction in mortality and a 39% reduction in first hospitalization for heart failure[2][5].

V-HeFT Trials

The Vasodilator-Heart Failure Trials (V-HeFT I and II) laid the groundwork for the A-HeFT trial by indicating a survival benefit with the use of vasodilator therapy, including isosorbide dinitrate and hydralazine hydrochloride, in heart failure patients. These trials highlighted the potential benefits of this combination, especially in African-American patients[2].

Community Sample Studies

A retrospective cohort study involving 76,828 veterans with heart failure further explored the effectiveness of isosorbide dinitrate and hydralazine hydrochloride in a broader population. The study found that African-American patients benefited more significantly from this combination compared to Hispanic or White patients, with lower risks of mortality and hospitalization[1].

Market Analysis

FDA Approval and Market Exclusivity

BiDil was approved by the FDA in 2005, marking the first drug approved specifically for the treatment of heart failure in African-American patients. The approval was based on the positive outcomes of the A-HeFT trial. The drug's market exclusivity was a critical factor, as it encouraged the development of targeted therapies for specific population groups[2].

Targeted Population Strategies

The success of BiDil underscores the importance of tailored communication and marketing strategies for medications targeting specific populations. The pharmaceutical industry has learned from BiDil that recognizing and addressing the unique healthcare needs of diverse population groups can be both medically and commercially viable[2].

Access and Affordability

Despite its benefits, BiDil faces challenges related to access and affordability, particularly for low-income or uninsured populations. Ensuring that targeted healthcare technologies are accessible to all segments of the population remains a significant issue in the healthcare and pharmaceutical industries[2].

Pharmacokinetics and Hemodynamic Effects

Mechanism of Action

The combination of isosorbide dinitrate and hydralazine hydrochloride works by enhancing nitric oxide levels and acting as an antioxidant, which helps prevent tolerance to prolonged nitrate use. This combination increases cardiac output, renal blood flow, and limb blood flow, thereby improving the functional status of patients with heart failure[4][5].

Dosage and Administration

BiDil is administered in a fixed-dose combination of 20 mg isosorbide dinitrate and 37.5 mg hydralazine hydrochloride, typically one to two tablets three times a day. The dosage can be adjusted based on tolerance and side effects[4].

Safety and Adverse Reactions

Contraindications

BiDil is contraindicated in patients allergic to organic nitrates and those using phosphodiesterase type 5 (PDE5) inhibitors. Common adverse reactions include palpitations, vomiting, and amblyopia. Serious reactions such as blood dyscrasias, agranulocytosis, and psychotic reactions have also been reported[4].

Market Projections

Growing Demand for Heart Failure Treatments

With over 5 million people diagnosed with heart failure in the USA alone, and a disproportionate number of African-Americans affected, the demand for effective treatments like BiDil is expected to grow. The increasing diversity of the US population will continue to drive the need for targeted therapies[5].

Expansion to Other Population Groups

While BiDil was initially approved for African-American patients, future clinical trials may explore its benefits in other racial and ethnic groups. This could expand the market potential of the drug and address the underrepresentation of diverse populations in clinical trials[5].

Competitive Landscape

The heart failure treatment market is competitive, with various drugs and therapies available. However, BiDil's unique positioning as a targeted therapy for African-American patients gives it a niche market advantage. As the pharmaceutical industry continues to diversify its product offerings, BiDil is likely to remain a significant player in the heart failure treatment segment[2].

Key Takeaways

• Clinical Efficacy: BiDil has demonstrated a significant reduction in mortality and hospitalization rates among African-American patients with heart failure.
• Market Exclusivity: FDA approval and market exclusivity have been crucial in encouraging the development of targeted therapies.
• Pharmacokinetics: The combination enhances nitric oxide levels and improves cardiac output, with specific dosage and administration guidelines.
• Safety Profile: While generally well-tolerated, BiDil has contraindications and potential adverse reactions that need to be monitored.
• Market Potential: Growing demand for heart failure treatments and potential expansion to other population groups suggest a positive market outlook.

FAQs

Q: What is BiDil, and how does it work?

A: BiDil is a fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride. It works by enhancing nitric oxide levels and acting as an antioxidant, which helps improve cardiac output and reduce tolerance to prolonged nitrate use.

Q: Who is BiDil primarily approved for?

A: BiDil is primarily approved for the treatment of heart failure in African-American patients with NYHA class III or IV heart failure.

Q: What were the key findings of the A-HeFT trial?

A: The A-HeFT trial showed a 43% reduction in mortality and a 39% reduction in first hospitalization for heart failure among African-American patients treated with BiDil.

Q: What are the common adverse reactions associated with BiDil?

A: Common adverse reactions include palpitations, vomiting, and amblyopia. Serious reactions such as blood dyscrasias and psychotic reactions have also been reported.

Q: Is BiDil contraindicated in any specific patient groups?

A: Yes, BiDil is contraindicated in patients allergic to organic nitrates and those using phosphodiesterase type 5 (PDE5) inhibitors.

Sources

1. Effectiveness of Isosorbide Dinitrate and Hydralazine in Racial ... - Effective Healthcare Research Information.
2. Communication Strategies Must Be Tailored to a Medication's ... - AHDB Online.
3. BiDil for Heart Failure in Black Patients: The U.S. Food and Drug ... - ResearchGate.
4. Isosorbide dinitrate and hydralazine hydrochloride - FDA.
5. Isosorbide dinitrate and hydralazine hydrochloride - PubMed - PubMed.