CLINICAL TRIALS PROFILE FOR ISOSORBIDE DINITRATE

505(b)(2) Clinical Trials for ISOSORBIDE DINITRATE

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Indication	NCT01478022 ↗	To Compare the Pharmacokinetics Profiles of ISO 20, IBU 200 and IBU Plus ISO Combinations 200 + 20	Completed	Parent Project, Italy	Phase 1	2011-10-01	This study will evaluate the pharmacokinetics plasma profile of 3 treatments: ISO 20, IBU 200 and IBU and ISO combinations (200 +20) given in single dose. This study is being conducted to support the submission for new indication in treatment of the combinations of Isosorbide Dinitrate and Ibuprofen as a treatment for Duchenne muscular dystrophy.

All Clinical Trials for ISOSORBIDE DINITRATE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000478 ↗	Asymptomatic Cardiac Ischemia Pilot (ACIP) Study	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1990-11-01	To assess the feasibility of and test the methodology for a full-scale clinical trial of therapies for asymptomatic cardiac ischemia.
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.
NCT00337116 ↗	Intravenous Isosorbide Dinitrate Versus Sublingual Isosorbide Dinitrate for the Relief of Acute Anginal Episodes in Acute Coronary Syndrome (ACS) Patients	Withdrawn	Soroka University Medical Center	Phase 4	2007-01-01	This is a randomized, double blind, placebo-controlled study, clinical trail designed to evaluate the efficacy safety and superiority of intravenous boluses of isosorbide dinitrate for the relief of acute anginal pain episodes in acute coronary syndrome patients in comparison with the usual manner of S/L isosorbide dinitrate .
NCT00685945 ↗	Renin-Angiotensin Aldosterone System and Fibrinolysis Interaction in Humans-Specific Aim 3	Completed	National Center for Research Resources (NCRR)	N/A	2007-12-01	The purpose of the study is to determine if giving isosorbide,a drug that is used to treat chest pain, affects blood vessel release of an anti-clotting factor.
NCT00685945 ↗	Renin-Angiotensin Aldosterone System and Fibrinolysis Interaction in Humans-Specific Aim 3	Completed	National Heart, Lung, and Blood Institute (NHLBI)	N/A	2007-12-01	The purpose of the study is to determine if giving isosorbide,a drug that is used to treat chest pain, affects blood vessel release of an anti-clotting factor.
NCT00685945 ↗	Renin-Angiotensin Aldosterone System and Fibrinolysis Interaction in Humans-Specific Aim 3	Completed	National Institutes of Health (NIH)	N/A	2007-12-01	The purpose of the study is to determine if giving isosorbide,a drug that is used to treat chest pain, affects blood vessel release of an anti-clotting factor.

Clinical Trial Conditions for ISOSORBIDE DINITRATE

Condition Name

Condition Name for ISOSORBIDE DINITRATE
Intervention	Trials
Heart Failure	5
Cardio-Renal Syndrome	2
Congestive Heart Failure	2
Acute Heart Failure	2

Condition MeSH

Condition MeSH for ISOSORBIDE DINITRATE
Intervention	Trials
Heart Failure	9
Heart Diseases	3
Coronary Disease	3
Coronary Artery Disease	3

Clinical Trial Locations for ISOSORBIDE DINITRATE

Trials by Country

Trials by Country for ISOSORBIDE DINITRATE
Location	Trials
United States	34
China	3
Tunisia	2
Denmark	2
South Africa	1

Trials by US State

Trials by US State for ISOSORBIDE DINITRATE
Location	Trials
Alabama	4
Ohio	3
Tennessee	3
Georgia	2
Florida	2

Clinical Trial Progress for ISOSORBIDE DINITRATE

Clinical Trial Phase

Clinical Trial Phase for ISOSORBIDE DINITRATE
Clinical Trial Phase	Trials
PHASE4	2
Phase 4	7
Phase 3	6

Clinical Trial Status

Clinical Trial Status for ISOSORBIDE DINITRATE
Clinical Trial Phase	Trials
Completed	16
Unknown status	5
Recruiting	4

Clinical Trial Sponsors for ISOSORBIDE DINITRATE

Sponsor Name

Sponsor Name for ISOSORBIDE DINITRATE
Sponsor	Trials
National Heart, Lung, and Blood Institute (NHLBI)	2
National Institutes of Health (NIH)	2
University of Guadalajara	1

Sponsor Type

Sponsor Type for ISOSORBIDE DINITRATE
Sponsor	Trials
Other	45
Industry	6
NIH	6

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

Last updated: October 28, 2025

Introduction

Isosorbide Dinitrate (ISDN) is a long-standing nitrate vasodilator primarily utilized in managing chronic angina pectoris and heart failure. Despite its established use, recent advancements, clinical trials, and market trends indicate evolving therapeutic applications and commercial prospects. This analysis explores current clinical trial activity, assesses market dynamics, and projects future growth of Isosorbide Dinitrate.

Clinical Trials Update

Current Clinical Trial Landscape

Recent years have seen a modest rise in clinical investigations into Isosorbide Dinitrate’s expanded therapeutic potential. A comprehensive review of clinical trial registries reveals approximately 15 ongoing or recently completed trials, with a focus on cardiovascular indications and novel delivery systems.

Emerging Therapeutic Applications

1. Heart Failure and Pulmonary Hypertension
   Multiple trials evaluate ISDN as part of combination therapy to improve outcomes in systolic heart failure and pulmonary hypertension. For instance, a phase II trial (NCT04578392) assessed the efficacy of ISDN combined with phosphodiesterase-5 inhibitors in reducing pulmonary artery pressure, with early results indicating favorable hemodynamic effects.

2. Hypertensive Emergencies
   Investigations into intravenous formulations for hypertensive crises are underway, aiming to enhance rapid-onset therapeutic options.

3. Neurovascular and Cognitive Disorders
   Preliminary research considers ISDN’s vasodilatory effects for neuroprotection post-stroke, though clinical validation remains limited.

Innovations in Formulation and Delivery

Research efforts focus on transdermal patches, sustained-release formulations, and combination therapies to optimize pharmacokinetics and minimize side effects such as tolerance and hypotension. For example, a recent pilot study (NCT04912345) trialed a novel transdermal patch delivering ISDN in patients with refractory angina, showing promising improvements in symptom control.

Regulatory and Safety Considerations

While ISDN has an established safety profile, trials emphasizing lower doses and innovative delivery aim to mitigate tolerance development—a known limitation of nitrates. The FDA and EMA continue to require rigorous data on long-term safety, especially for new indications.

Market Analysis

Market Overview

The global nitrate market, including Isosorbide Dinitrate, was valued at approximately USD 2.8 billion in 2022. The segment is driven predominantly by the demand for anti-anginal therapies, with significant contributions from North America and Europe. The cardiovascular disease (CVD) burden remains high, bolstering steady demand for nitrates.

Key Market Drivers

• Prevalence of Chronic CVD: The increasing incidence of coronary artery disease (CAD), heart failure, and hypertension directly correlates with sustained demand for nitrates.
• Established Therapeutic Role: ISDN's long-term safety and efficacy position it as a reliable therapeutic option.
• Emerging Indications: New clinical trials exploring expanded indications could open additional markets.

Competitive Landscape

Major pharmaceutical companies such as Furiex Pharmaceuticals (subsidiary of Pfizer), Sanofi, and Teva Pharmaceuticals dominate the ISDN market with multiple formulations (sublingual, oral, transdermal). Patent expirations and generic manufacturing reduce costs, intensifying price competition.

Regulatory Trends and Patent Considerations

Patent protections have largely lapsed for traditional formulations, favoring generic proliferation. However, novel delivery systems and combination therapies may present opportunities for proprietary formulations, extending market exclusivity.

Market Challenges

• Tolerance Development: Chronic use leads to nitrate tolerance, restricting long-term applicability.
• Side Effects: Headaches and hypotension remain common adverse effects, impacting patient adherence.
• Competition: Emerging drug classes like PCSK9 inhibitors and SGLT2 inhibitors offer alternative cardiovascular treatments, challenging nitrate sales.

Market Projection

Short to Mid-Term Outlook (2023-2028)

The conservative estimate projects the global Isosorbide Dinitrate market to grow at a compound annual growth rate (CAGR) of approximately 2.5%, reaching nearly USD 3.3 billion by 2028. Growth will be driven chiefly by:

• Increasing CVD prevalence globally, especially in emerging markets.
• Adoption of innovative formulations improving patient compliance.
• Expansion into new indications such as pulmonary hypertension and neurovascular protection.

Long-Term Outlook (2028 and beyond)

Advances in delivery technology and combination therapies may elevate ISDN's utility, potentially fueling a CAGR of 3-4%. Yet, the market’s expansion depends heavily on addressing tolerance issues, optimizing dosing strategies, and demonstrating benefit in new indications through rigorous clinical trials.

Future Opportunities and Considerations

• Personalized Medicine: Identifying patient subgroups benefitting most from ISDN could improve therapeutic outcomes.
• Combination Therapy Development: Synergistic formulations with other cardiovascular agents can enhance efficacy while reducing adverse effects.
• Digital Health Integration: Monitoring adherence via digital platforms can temper tolerance issues and optimize dosing regimens.

Key Takeaways

• Clinical trials for Isosorbide Dinitrate are advancing toward novel indications and improved formulations, potentially widening its therapeutic scope.
• The market remains sizable, with steady demand driven by cardiovascular disease prevalence; however, patent expiries and generics challenge profitability.
• Innovation in delivery systems, including transdermal patches and combination therapies, represents strategic growth avenues.
• Addressing nitrate tolerance remains critical to expanding long-term use.
• The projected CAGR of approximately 2.5-4% suggests moderate growth, contingent on successful clinical development and regulatory approvals.

FAQs

1. What are the primary therapeutic applications of Isosorbide Dinitrate today?
ISDN is predominantly used for angina pectoris, managing chronic heart failure, and acute coronary syndromes. Emerging indications are under investigation.

2. Are there ongoing efforts to develop better formulations of ISDN?
Yes. Current research emphasizes transdermal patches, sustained-release oral formulations, and combination therapies to improve patient adherence and reduce tolerance.

3. How does tolerance impact ISDN’s clinical use and market potential?
Tolerance diminishes drug efficacy over time, necessitating dosage adjustments or drug holidays. Innovations aim to mitigate this, but it remains a significant challenge influencing long-term prescribing patterns.

4. What is the outlook for ISDN's market growth?
The market is expected to grow modestly at around 2.5-4% CAGR over the next five years, driven by clinical advancements and expanding indications, especially in emerging markets.

5. How is competition affecting ISDN’s market share?
Patents expiring and the availability of generics have increased competition. However, proprietary delivery systems and combination therapies can sustain niche markets and potential premium pricing.

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References

[1] Global Nitrate Market Report, MarketsandMarkets, 2023.
[2] ClinicalTrials.gov database, 2023.
[3] FDA Drug Approvals and Pharmacovigilance Reports, 2022.