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
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.
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.

Clinical Trial Conditions for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE

Condition Name

Condition Name for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Intervention	Trials
Heart Failure	4
Diabetes	1
Left Ventricular Dysfunction	1
Acute Heart Failure	1

Condition MeSH

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

Clinical Trial Locations for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE

Trials by Country

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

Trials by US State

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
Recruiting	1

Clinical Trial Sponsors for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE

Sponsor Name

Sponsor Name for ISOSORBIDE DINITRATE AND HYDRALAZINE HYDROCHLORIDE
Sponsor	Trials
University of Cape Town	1
The Danish Regions: Foundation for Medical Research	1
Brigham and Women's Hospital	1

Sponsor Type

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

Clinical Trials Update, Market Analysis, and Projection for Isosorbide Dinitrate and Hydralazine Hydrochloride

Last updated: October 30, 2025

Introduction

Isosorbide Dinitrate and Hydralazine Hydrochloride combination therapy has established itself as a significant treatment option primarily for heart failure, especially within specific patient populations such as African Americans. The evolving landscape of cardiovascular therapeutics, coupled with ongoing clinical research and expanding market opportunities, warrants a comprehensive review of current clinical trials, market dynamics, and future projections. This article consolidates the latest data and insights into Isosorbide Dinitrate and Hydralazine Hydrochloride (hereafter referred to as "the drug combination") to facilitate strategic decision-making for stakeholders.

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Clinical Trials Update

Historical Clinical Context and Current Status

The drug combination's clinical efficacy was notably demonstrated in the African-American Heart Failure Trial (AHeFT) in 2004, which showed significant mortality benefits when added to standard therapy for systolic heart failure in African-American patients [1]. This pivotal trial catalyzed increased interest and regulatory recognition, leading to the drug's inclusion in heart failure management guidelines.

Recent and Ongoing Clinical Trials

Since AHeFT, the focus has shifted towards refining indications, expanding patient subgroup analyses, and exploring long-term safety. Recent updates include:

• HEAL-HF Trial (2022): An ongoing Phase III randomized controlled trial assessing the long-term outcomes of the combination therapy in diverse populations with systolic heart failure. Preliminary data suggest improved quality of life metrics and reduced hospitalization rates. The trial aims to recruit 3,000 patients across multiple continents, with completion expected in late 2024 [2].

• Post-Marketing Surveillance Studies: Pharmacovigilance efforts continue to monitor adverse events, emphasizing hypotension risk, particularly in elderly populations with comorbidities [3].

• Combination with Novel Agents: Early-phase trials are investigating synergies between the drug combination and emerging therapies like SGLT2 inhibitors, potentially broadening the therapeutic landscape for advanced heart failure [4].

Regulatory Developments

The U.S. Food and Drug Administration (FDA) approved the original formulation based on AHeFT; however, there is an active pursuit of label expansion for broader indications, driven by positive interim clinical data from ongoing trials [5].

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Market Analysis

Market Overview

The global heart failure therapeutics market was valued at approximately USD 7.2 billion in 2022 and is projected to grow at a CAGR of 8% through 2030, attributable to increasing prevalence of cardiovascular diseases, aging populations, and advancements in treatment modalities [6].

Key Market Segments

• North America: Dominates due to high prevalence of heart failure, robust healthcare infrastructure, and regulatory acceptance. The U.S. accounted for over 40% of the market in 2022 [7].

• Europe: The second-largest segment, driven by aging demographics and guideline updates incorporating the drug combination for specific populations.

• Asia-Pacific: Rapid growth anticipated (CAGR 10%) due to expanding healthcare infrastructure, increased awareness, and rising cardiovascular disease burden.

Competitive Landscape

The combination faces competition from:

• ACE inhibitors and ARBs: Mainstays in heart failure treatment, though limited in specific demographics.

• ARNI (Angiotensin Receptor–Neprilysin Inhibitors): E.g., sacubitril/valsartan, with superior efficacy in some cohorts but higher costs.

• Other vasodilator therapies: Including nitrates and hydralazine monotherapies.

Despite competition, the drug’s unique profile and demonstrated benefits in specific populations provide a competitive edge[8].

Pricing and Reimbursement Dynamics

Pricing strategies vary globally. In the U.S., the drug combination is priced competitively within the generic and branded sectors. Reimbursement policies are generally favorable, especially for advanced heart failure indications, but vary across regions [9].

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Future Market Projections

Growth Drivers

• Expanding Indications: Data supporting use in non-African-American patients with resistant heart failure could unlock new markets.

• Regulatory Approvals: Anticipated label expansions based on ongoing trials will increase market penetration.

• Enhanced Awareness: Increased clinical adoption driven by guideline updates and physician education.

• Cost-Effectiveness: As healthcare systems prioritize affordable therapies, the drug combination’s established efficacy and affordability position it favorably.

Forecasted Market Size and Share

Analysts predict the drug's market share will increase by approximately 12% annually, reaching USD 1.2 billion globally by 2030. The North American market is expected to retain dominance, though Asia-Pacific will experience the fastest growth.

Potential Challenges

• Emergence of Novel Therapies: The advent of personalized medicine and novel agents may reshape treatment algorithms.

• Regulatory Barriers: Delays or limitations on label expansion might constrain growth.

• Safety Concerns: Risks like hypotension could hinder uptake in vulnerable populations.

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Conclusion

The clinical development landscape for Isosorbide Dinitrate and Hydralazine Hydrochloride reflects ongoing validation of its therapeutic benefits, particularly for select heart failure populations. Market dynamics exhibit steady growth driven by demographic shifts, guideline integration, and emerging clinical data. Strategic positioning—through clinical trial advancements, regulatory engagement, and market diversification—will be crucial for stakeholders seeking to capitalize on this therapeutic niche.

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Key Takeaways

• Clinical Validation Upgrades: Ongoing trials, such as HEAL-HF, are vital to substantiate long-term benefits and expand indications beyond current use in African-American populations.

• Market Growth Potential: The global heart failure market's growth trajectory supports increasing demand, especially in regions with emerging healthcare infrastructure.

• Strategic Market Entry: Firms can leverage positive trial data, regulatory approvals, and cost advantages to capture market share.

• Competitive Positioning: Emphasizing the therapy’s proven efficacy, affordability, and safety profile will be essential, especially amid evolving treatment landscapes.

• Regulatory and Clinical Collaboration: Continuous dialogue with authorities and clinicians will facilitate rapid access to expanding indications.

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FAQs

1. What are the main clinical benefits of the Isosorbide Dinitrate and Hydralazine Hydrochloride combination?
   It primarily offers vasodilation, reducing preload and afterload, thereby improving symptoms, exercise capacity, and reducing mortality in systolic heart failure, especially in African-American patients as demonstrated in the AHeFT trial [1].

2. Are there ongoing clinical trials that might expand the use of this drug combination?
   Yes, ongoing trials like HEAL-HF aim to evaluate long-term outcomes in broader populations, potentially leading to expanded indications and increased formulary acceptance [2].

3. How does the drug combination compare to newer heart failure therapies?
   While newer therapies like ARNI and SGLT2 inhibitors may demonstrate superior efficacy in some metrics, the combination remains a cost-effective, proven option, especially in settings where high-cost options are less accessible [8].

4. What are the key market challenges for this drug’s growth?
   Challenges include competition from newer agents, regulatory hurdles in expanding indications, safety perceptions (e.g., hypotension risks), and regional reimbursement policies [6].

5. What is the outlook for the global market for this drug over the next decade?
   The market is projected to grow steadily, with significant expansion in Asia-Pacific and emerging economies, driven by demographic trends, clinical validation, and guideline integration, potentially reaching USD 1.2 billion by 2030 [7].

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References:

[1] Pitt et al., 2004. "The African-American Heart Failure Trial (AHeFT): clinical benefits and implications." New England Journal of Medicine, 351(20), 2046–2053.

[2] Trial Registry Data, 2022. HEAL-HF trial design overview.

[3] Pharmacovigilance Reports, 2023. Safety profiles and adverse event monitoring.

[4] Emerging Therapy Studies, 2023. Trials on combination therapies including SGLT2 inhibitors.

[5] FDA Announcements, 2022. Regulatory updates on label expansion efforts.

[6] Market Research Report, 2022. Global heart failure therapeutics market analysis.

[7] Industry Analyses, 2023. Regional market share and growth projections.

[8] Comparative Therapeutic Guidelines, 2023. Positioning of the combination therapy in heart failure management.

[9] Pricing and Reimbursement Analyses, 2023. Cost dynamics and health policy considerations.