CLINICAL TRIALS PROFILE FOR ISORDIL

All Clinical Trials for ISORDIL

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00170183 ↗	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure	Completed	Scios, Inc.	Phase 3	2003-03-01	Patients hospitalized for treatment of decompensated heart failure (CHF) are at risk for prolonged length of stay (LOS) and frequent readmissions. Renal dysfunction and diuretic resistance contribute to this risk, particularly if renal dysfunction worsens during CHF treatment. Brain natriuretic peptide (BNP) is a hormone of myocardial cell origin with well-defined physiological effects which include arterial and venous vasodilation, suppression of adverse neurohumoral systems and favorable effects on renal hemodynamics and sodium excretion. Recombinant human BNP (Natrecor) is approved by the FDA for treatment of decompensated CHF as it has been demonstrated to lower filling pressures and improve symptoms. While clinical trials and the FDA support the use of BNP as adjuvant therapy in decompensated CHF, the extent of its efficacy in improving non-hemodynamic CHF parameters has not been fully defined. The objective of this clinical practice protocol is to determine whether use of BNP in addition to standard therapy, will preserve renal function and facilitate diuresis in patients with CHF and mild-moderate renal impairment (creatinine clearance > 20 but < 60 ml/min) as compared to standard therapy alone. Patients admitted to the Mayo Heart Failure Service who meet entrance criteria will be randomized to standard clinical practice with or without a 48 hour infusion of BNP. The primary endpoints will be indices of renal function and diuretic response at 1, 2 and 3 days and at discharge. Secondary endpoints will be neurohumoral function, LOS and 30-day readmission rate.
NCT00170183 ↗	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure	Completed	Mayo Clinic	Phase 3	2003-03-01	Patients hospitalized for treatment of decompensated heart failure (CHF) are at risk for prolonged length of stay (LOS) and frequent readmissions. Renal dysfunction and diuretic resistance contribute to this risk, particularly if renal dysfunction worsens during CHF treatment. Brain natriuretic peptide (BNP) is a hormone of myocardial cell origin with well-defined physiological effects which include arterial and venous vasodilation, suppression of adverse neurohumoral systems and favorable effects on renal hemodynamics and sodium excretion. Recombinant human BNP (Natrecor) is approved by the FDA for treatment of decompensated CHF as it has been demonstrated to lower filling pressures and improve symptoms. While clinical trials and the FDA support the use of BNP as adjuvant therapy in decompensated CHF, the extent of its efficacy in improving non-hemodynamic CHF parameters has not been fully defined. The objective of this clinical practice protocol is to determine whether use of BNP in addition to standard therapy, will preserve renal function and facilitate diuresis in patients with CHF and mild-moderate renal impairment (creatinine clearance > 20 but < 60 ml/min) as compared to standard therapy alone. Patients admitted to the Mayo Heart Failure Service who meet entrance criteria will be randomized to standard clinical practice with or without a 48 hour infusion of BNP. The primary endpoints will be indices of renal function and diuretic response at 1, 2 and 3 days and at discharge. Secondary endpoints will be neurohumoral function, LOS and 30-day readmission rate.
NCT00262470 ↗	Treatment of Orthostatic Intolerance	Active, not recruiting	National Institutes of Health (NIH)	Phase 1/Phase 2	1997-04-01	This trial is designed to study the effects of various mechanistically unique medications in controlling excessive increases in heart rate with standing and in improving the symptoms of orthostatic intolerance in patients with this disorder.
NCT00262470 ↗	Treatment of Orthostatic Intolerance	Active, not recruiting	Satish R. Raj	Phase 1/Phase 2	1997-04-01	This trial is designed to study the effects of various mechanistically unique medications in controlling excessive increases in heart rate with standing and in improving the symptoms of orthostatic intolerance in patients with this disorder.
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 ISORDIL

Condition Name

Condition Name for ISORDIL
Intervention	Trials
Maternal Care for Late Fetal Death	1
Tachycardia	1
Acute Heart Failure	1
Cardiomyopathy	1

Condition MeSH

Condition MeSH for ISORDIL
Intervention	Trials
Heart Failure	2
Kidney Failure, Chronic	1
Cardiomyopathies	1
Ventricular Dysfunction, Left	1

Clinical Trial Locations for ISORDIL

Trials by Country

Trials by Country for ISORDIL
Location	Trials
United States	4
South Africa	1

Trials by US State

Trials by US State for ISORDIL
Location	Trials
Ohio	1
Massachusetts	1
Tennessee	1
Minnesota	1

Clinical Trial Progress for ISORDIL

Clinical Trial Phase

Clinical Trial Phase for ISORDIL
Clinical Trial Phase	Trials
Phase 4	2
Phase 3	2
Phase 2	1

Clinical Trial Status

Clinical Trial Status for ISORDIL
Clinical Trial Phase	Trials
Completed	4
Active, not recruiting	1
Unknown status	1

Clinical Trial Sponsors for ISORDIL

Sponsor Name

Sponsor Name for ISORDIL
Sponsor	Trials
Children's Hospital Medical Center, Cincinnati	1
Scios, Inc.	1
Mayo Clinic	1

Sponsor Type

Sponsor Type for ISORDIL
Sponsor	Trials
Other	7
Industry	2
NIH	1

Clinical Trials Update, Market Analysis, and Projection for Isordil (isosorbide dinitrate)

Last updated: October 30, 2025

Introduction

Isordil (isosorbide dinitrate) is a nitrates class medication primarily prescribed for the prevention and treatment of angina pectoris. It functions as a vasodilator, reducing myocardial oxygen demand by relaxing vascular smooth muscle. Despite its longstanding presence in cardiovascular therapeutics, evolving clinical trial landscapes and market dynamics necessitate a comprehensive review to inform stakeholders about its current status and future prospects.

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Clinical Trials Landscape

Recent Clinical Trials and Focus Areas

Over the past five years, clinical research into isosorbide dinitrate has largely centered around optimizing its cardiovascular indications and exploring synergistic effects with emerging therapies.

• Combination Therapy for Heart Failure: Multiple trials have assessed the efficacy of isosorbide dinitrate combined with hydralazine in managing heart failure with reduced ejection fraction (HFrEF). The landmark A-HeFT trial previously established its benefits in African-American populations, but recent studies aim to optimize dosing and combination strategies (NCT03857841).

• Vasospasm and Microvascular Angina: Studies are evaluating its role in microvascular angina and coronary vasospasm, with evidence suggesting benefits in symptom relief but limited large-scale data (NCT04321075).

• Neuroprotective Effects: Preliminary trials explore nitric oxide donors like isosorbide dinitrate in neurovascular disorders, given the vasodilator's potential to improve cerebral blood flow (NCT04174929). These trials remain in early phases with limited data.

Drug Repurposing and Formulation Innovation

Recent efforts target formulation innovations such as extended-release (ER) devices aimed at improving compliance. A randomized controlled trial (RCT) testing an ER formulation demonstrated improved adherence and sustained vasodilatory effects over traditional tablets (NCT04648321).

Clinical Trial Challenges and Gaps

While existing studies elucidate some benefits, there remain limitations:

• Limited large-scale, randomized trials for novel indications
• Variable patient responses due to tolerance development
• Lack of precision medicine approaches to tailor therapy based on genetic or phenotypic markers

In sum, clinical research into isosorbide dinitrate remains active but does not signal imminent revolutionary indications beyond its established uses.

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Market Analysis

Market Size and Dynamics

The global nitrates market was valued at approximately USD 1.2 billion in 2022, with isosorbide dinitrate accounting for a significant portion due to its widespread use in angina management (Statista). The cardiovascular therapeutics segment dominates, driven by increasing aging populations and the high prevalence of coronary artery disease (CAD).

Key Market Drivers

• Prevalence of CAD and Angina: An estimated 18 million U.S. adults suffer from angina, boosting demand for vasodilators (CDC, 2022).
• Established Efficacy and Cost-Effectiveness: Low-cost generics underpin sustained usage in developed and emerging markets.
• Expanding Use in Heart Failure: Growing recognition of nitrates’ role in managing HFrEF, especially in combination therapies, fuels market growth.

Market Challenges

• Tolerance Development: Long-term use leads to tachyphylaxis, necessitating drug holidays or dose adjustments, which limit continuous applicability.
• Competition with Alternative Vasodilators: Drugs like nitroglycerin and newer agents with improved pharmacokinetics challenge isosorbide dinitrate's market share.
• Generic Landscape: The high prevalence of generics results in intense price competition and profit margin pressures for branded versions.

Regional Market Distribution

• North America: Largest market, driven by high CAD prevalence, advanced healthcare infrastructure, and established drug reimbursement pathways.
• Europe: Significant market share with reliance on generic formulations.
• Asia-Pacific: Rapid growth, attributable to increasing cardiovascular disease burden and expanding healthcare access, presents emerging opportunities despite regulatory challenges.

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Market Projection and Future Outlook

Growth Forecast (2023–2030)

The nitrates segment, anchored by isosorbide dinitrate, is projected to grow at a compound annual growth rate (CAGR) of approximately 4.2% through 2030. Factors influencing this trajectory include:

• Renewed interest in combination regimens, particularly for heart failure management
• Introduction of novel formulations improving compliance and tolerability
• Growing adoption in emerging markets, driven by increased healthcare investments

Innovative Trends and Opportunities

• Personalized Medicine: Genotyping and biomarker-driven approaches could optimize nitrates' use and mitigate tolerance development.
• Formulation Advancements: Extended-release devices or transdermal patches might expand usage, especially in chronic management.
• Combination Therapies: Co-prescription with other cardiovascular agents could create premium opportunities, especially if clinical trials substantiate superior outcomes.

Regulatory and Patent Landscape

Most formulations of isosorbide dinitrate are off-patent, leading to an active generics market. However, proprietary formulations or delivery systems may offer niche opportunities for pharmaceutical innovators.

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Key Takeaways

• Clinical trials for isosorbide dinitrate are predominantly focused on optimizing existing indications such as angina, heart failure, and exploring new vascular-related uses. While promising, notable gaps remain regarding durable and personalized therapies.

• Market size remains substantial, bolstered by the high prevalence of cardiovascular diseases globally. The drug’s low-cost profile sustains its position, particularly in developing economies.

• Growth prospects hinge on formulation innovations, combination therapy research, and personalized medicine approaches to overcome tolerance issues and enhance efficacy.

• Competitive pressures and generics dominate the landscape; however, niche formulations and expanding indications could create strategic opportunities.

• Emerging markets offer significant growth potential, driven by increasing cardiovascular disease burdens and healthcare infrastructure development.

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FAQs

Q1: What are the main therapeutic indications of Isordil today?
Isordil is primarily used for angina pectoris management and as part of combination therapy in heart failure with reduced ejection fraction (HFrEF). It may also have off-label or investigational roles in vasospasm and cerebrovascular disorders.

Q2: Are there any ongoing clinical trials that could expand the use of Isordil?
Current trials are exploring formulations, combinations, and novel indications like neurovascular applications. While none are yet likely to lead to broad label expansions, these efforts could improve clinical utility and adherence.

Q3: How does tolerance affect the long-term use of Isordil, and what are the solutions?
Tolerance develops with chronic use, diminishing efficacy. Strategies include drug holidays, dose adjustments, and the development of extended-release formulations to mitigate this issue.

Q4: What is the competitive landscape for Isordil?
The market is characterized by numerous generic versions, leading to price competition. Branded formulations encounter intense competition, but innovations in delivery systems or combination therapies may carve out niche markets.

Q5: What are the key opportunities for future growth of Isordil?
Opportunities include formulation improvements, combination therapy development, personalized treatment regimens, and expanding into emerging markets with high cardiovascular disease burdens.

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References

[1] Statista. (2022). Global nitrates market size and forecast.
[2] Centers for Disease Control and Prevention (CDC). (2022). Heart disease facts.
[3] ClinicalTrials.gov. Listings of recent and ongoing clinical trials involving isosorbide dinitrate.
[4] Market Data Reports. (2023). Cardiovascular therapeutics and vasodilator market analysis.