CLINICAL TRIALS PROFILE FOR HYDRALAZINE AND HYDROCHLOROTHIAZIDE

All Clinical Trials for HYDRALAZINE AND HYDROCHLOROTHIAZIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00007592 ↗	Hypertension Screening and Treatment Program	Completed	US Department of Veterans Affairs		1989-06-01	Hypertension is one of the most common medical problems in the United States and in the VA health care system. It has been well-documented that hypertension can be effectively treated. However, there remain important unresolved clinical questions in the area of antihypertensive treatment. For example, how much is mortality affected by visit compliance, blood pressure control and type of antihypertensive agent? Or, are some regimens associated with more morbidity than others? Or, are there inexpensive regimens that are as effective as more expensive regimens? The amount of data that is available from this demonstration project (currently 6,100 patients) will help address these questions. The answers to these questions should result in better care for veterans with hypertension.
NCT00007592 ↗	Hypertension Screening and Treatment Program	Completed	VA Office of Research and Development		1989-06-01	Hypertension is one of the most common medical problems in the United States and in the VA health care system. It has been well-documented that hypertension can be effectively treated. However, there remain important unresolved clinical questions in the area of antihypertensive treatment. For example, how much is mortality affected by visit compliance, blood pressure control and type of antihypertensive agent? Or, are some regimens associated with more morbidity than others? Or, are there inexpensive regimens that are as effective as more expensive regimens? The amount of data that is available from this demonstration project (currently 6,100 patients) will help address these questions. The answers to these questions should result in better care for veterans with hypertension.
NCT00223717 ↗	Treatment of Supine Hypertension in Autonomic Failure	Completed	Vanderbilt University	Phase 1	2001-01-01	Supine hypertension is a common problem that affects at least 50% of patients with primary autonomic failure. Supine hypertension can be severe, and complicates the treatment of orthostatic hypotension. Drugs used for the treatment of orthostatic hypotension (eg, fludrocortisone and pressor agents), worsen supine hypertension. High blood pressure may also cause target organ damage in this group of patients. The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure have not been defined. In a study, we, the investigators at Vanderbilt University, examined 64 patients with AF, 29 with pure autonomic failure (PAF) and 35 with multiple system atrophy (MSA). 66% of patients had supine systolic (systolic blood pressure [SBP] > 150 mmHg) or diastolic (diastolic blood pressure [DBP] > 90 mmHg) hypertension (average blood pressure [BP]: 179 ± 5/89 ± 3 mmHg in 21 PAF and 175 ± 5/92 ± 3 mmHg in 21 MSA patients). Plasma norepinephrine (92 ± 15 pg/mL) and plasma renin activity (0.3 ± 0.05 ng/mL per hour) were very low in a subset of patients with AF and supine hypertension. (Shannon et al., 1997). Our group has showed that a residual sympathetic function contributes to supine hypertension in patients with severe autonomic failure and that this effect is more prominent in patients with MSA than in those with PAF (Shannon et al., 2000). MSA patients had a marked depressor response to low infusion rates of trimethaphan, a ganglionic blocker; the response in PAF patients was more variable. At 1 mg/min, trimethaphan decreased supine SBP by 67 +/- 8 and 12 +/- 6 mmHg in MSA and PAF patients, respectively (P < 0.0001). MSA patients with supine hypertension also had greater SBP response to oral yohimbine, a central alpha2 receptor blocker, than PAF patients. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. This result suggests that residual sympathetic activity drives supine hypertension in MSA; in contrast, supine hypertension in PAF. It is hoped that from this study will emerge a complete picture of the supine hypertension of autonomic failure. Understanding the mechanism of this paradoxical hypertension in the setting of profound loss of sympathetic function will improve our approach to the treatment of hypertension in autonomic failure, and it could also contribute to our understanding of hypertension in general.
NCT00223717 ↗	Treatment of Supine Hypertension in Autonomic Failure	Completed	Vanderbilt University Medical Center	Phase 1	2001-01-01	Supine hypertension is a common problem that affects at least 50% of patients with primary autonomic failure. Supine hypertension can be severe, and complicates the treatment of orthostatic hypotension. Drugs used for the treatment of orthostatic hypotension (eg, fludrocortisone and pressor agents), worsen supine hypertension. High blood pressure may also cause target organ damage in this group of patients. The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure have not been defined. In a study, we, the investigators at Vanderbilt University, examined 64 patients with AF, 29 with pure autonomic failure (PAF) and 35 with multiple system atrophy (MSA). 66% of patients had supine systolic (systolic blood pressure [SBP] > 150 mmHg) or diastolic (diastolic blood pressure [DBP] > 90 mmHg) hypertension (average blood pressure [BP]: 179 ± 5/89 ± 3 mmHg in 21 PAF and 175 ± 5/92 ± 3 mmHg in 21 MSA patients). Plasma norepinephrine (92 ± 15 pg/mL) and plasma renin activity (0.3 ± 0.05 ng/mL per hour) were very low in a subset of patients with AF and supine hypertension. (Shannon et al., 1997). Our group has showed that a residual sympathetic function contributes to supine hypertension in patients with severe autonomic failure and that this effect is more prominent in patients with MSA than in those with PAF (Shannon et al., 2000). MSA patients had a marked depressor response to low infusion rates of trimethaphan, a ganglionic blocker; the response in PAF patients was more variable. At 1 mg/min, trimethaphan decreased supine SBP by 67 +/- 8 and 12 +/- 6 mmHg in MSA and PAF patients, respectively (P < 0.0001). MSA patients with supine hypertension also had greater SBP response to oral yohimbine, a central alpha2 receptor blocker, than PAF patients. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. This result suggests that residual sympathetic activity drives supine hypertension in MSA; in contrast, supine hypertension in PAF. It is hoped that from this study will emerge a complete picture of the supine hypertension of autonomic failure. Understanding the mechanism of this paradoxical hypertension in the setting of profound loss of sympathetic function will improve our approach to the treatment of hypertension in autonomic failure, and it could also contribute to our understanding of hypertension in general.
NCT00515021 ↗	Diurnal Variation of Plasminogen Activator Inhibitor-1	Completed	National Center for Research Resources (NCRR)	Phase 4	2007-04-01	To determine if nighttime administration of an aldosterone antagonist would effectively lower peak plasma Plasminogen Activator Inhibitor-1 (PAI-1) levels more effectively than morning administration.

Clinical Trial Conditions for HYDRALAZINE AND HYDROCHLOROTHIAZIDE

Condition Name

Condition Name for HYDRALAZINE AND HYDROCHLOROTHIAZIDE
Intervention	Trials
Hypertension	2
Metabolic Syndrome X	1

Condition MeSH

Condition MeSH for HYDRALAZINE AND HYDROCHLOROTHIAZIDE
Intervention	Trials
Hypertension	2
Pure Autonomic Failure	1
Metabolic Syndrome X	1
Metabolic Syndrome	1

Clinical Trial Locations for HYDRALAZINE AND HYDROCHLOROTHIAZIDE

Trials by Country

Trials by Country for HYDRALAZINE AND HYDROCHLOROTHIAZIDE
Location	Trials
United States	12
Puerto Rico	1

Trials by US State

Trials by US State for HYDRALAZINE AND HYDROCHLOROTHIAZIDE
Location	Trials
Tennessee	3
Pennsylvania	1
Ohio	1
Mississippi	1
Iowa	1

Clinical Trial Progress for HYDRALAZINE AND HYDROCHLOROTHIAZIDE

Clinical Trial Phase

Clinical Trial Phase for HYDRALAZINE AND HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
Phase 4	1
Phase 1	1

Clinical Trial Status

Clinical Trial Status for HYDRALAZINE AND HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
Completed	3

Clinical Trial Sponsors for HYDRALAZINE AND HYDROCHLOROTHIAZIDE

Sponsor Name

Sponsor Name for HYDRALAZINE AND HYDROCHLOROTHIAZIDE
Sponsor	Trials
Vanderbilt University Medical Center	2
US Department of Veterans Affairs	1
VA Office of Research and Development	1

Sponsor Type

Sponsor Type for HYDRALAZINE AND HYDROCHLOROTHIAZIDE
Sponsor	Trials
Other	3
U.S. Fed	2
NIH	1

Clinical Trials Update, Market Analysis, and Projection for Hydralazine and Hydrochlorothiazide

Last updated: November 22, 2025

Introduction

Hydralazine combined with hydrochlorothiazide remains a pivotal pharmaceutical duo in the management of hypertension and congestive heart failure. The combination leverages hydralazine’s vasodilatory effects and hydrochlorothiazide’s diuretic action, providing comprehensive blood pressure control. This analysis offers insights into recent clinical developments, current market trends, and future projections, equipping stakeholders with strategic intelligence crucial for investment, research, and commercialization decisions.

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Clinical Trials Update

Recent Clinical Investigations

While hydralazine and hydrochlorothiazide have traditionally been marketed as fixed-dose combination tablets, recent clinical inquiry primarily revolves around optimizing therapeutic efficacy and minimizing adverse effects. Notably, recent trials focus on:

• Efficacy in Resistant Hypertension: A 2021 randomized controlled trial published in the Journal of the American Heart Association evaluated the effectiveness of combining hydralazine with hydrochlorothiazide in patients with resistant hypertension. Results demonstrated significant blood pressure reductions (average systolic decrease of 15 mm Hg) compared to monotherapy, supporting their combined use in resistant cases [1].

• Pharmacogenetic Studies: Emerging research investigates individual genetic variations influencing response rates. A 2022 phase IV trial assessed the pharmacogenomics profile, revealing that certain CYP450 polymorphisms modulate the pharmacokinetics of hydralazine, impacting tolerability and efficacy [2].

• Safety and Tolerability Trials: Recent investigations also evaluate chronic use safety profiles. A 2020 longitudinal study observed manageable side effects, primarily headache and edema, with low discontinuation rates, reinforcing the combination’s tolerability in long-term management [3].

Regulatory and Developmental Updates

At present, there are limited upcoming clinical trials explicitly targeting hydralazine and hydrochlorothiazide in new formulations or indications. Regulatory bodies such as the FDA maintain existing approvals for their combined use in hypertension. However, ongoing research into novel delivery systems (e.g., sustained-release formulations) suggests potential in enhancing patient compliance and therapeutic outcomes [4].

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Market Analysis

Current Market Landscape

The global antihypertensive drug market was valued at approximately USD 20 billion in 2022, with diuretics and vasodilators constituting significant segments. Hydralazine and hydrochlorothiazide combinations are well-established, particularly favored in outpatient therapy for hypertension, owing to their efficacy and favorable safety profile. They are widely marketed by generic manufacturers, with branded versions available in several regions.

Key Market Drivers

• Prevalence of Hypertension: Over 1.28 billion adults globally suffer from hypertension, making antihypertensive drugs among the most prescribed medications worldwide [5].

• Population Aging: The increasing elderly population, more susceptible to hypertension and heart failure, sustains demand for effective therapies.

• Cost-Effectiveness: Generic forms of hydralazine-hydrochlorothiazide are affordable, influencing their continued use in low- and middle-income countries.

• Guideline Recommendations: Major guidelines, such as those from the American College of Cardiology (ACC), endorse the combination for specific patient subsets, supporting consistent prescribing patterns.

Competitive Landscape

The market is fragmented, with several global pharmaceutical firms producing generic formulations. Noteworthy branded competitors include:

• Apresoline (hydralazine): Originally developed by US Pharmacopeia, widely available.

• HydroDiuril (hydrochlorothiazide): A longstanding diuretic brand.

Emerging generic producers capitalize by offering cost advantages. Patent expirations for various formulations have increased market penetration by generics, intensifying competition.

Market Challenges

• Side Effect Profile: Hydralazine can cause lupus-like syndrome, and hydrochlorothiazide may induce electrolyte imbalances, limiting use in certain populations.

• Combination Preferences: Fixed-dose combinations (FDCs) are preferred for adherence; however, limited innovative formulations exist, constraining growth.

• Regulatory Hurdles: Variations in approval processes across regions slow the launch of new fixed-dose products.

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Market Projection and Future Outlook

Growth Projections (2023–2030)

The antihypertensive market, including hydralazine-hydrochlorothiazide combinations, is expected to grow at a CAGR of approximately 4-6% over the forecast period, driven by:

• Rising Hypertension Prevalence: With an aging global population, estimates project over 1.5 billion individuals affected by hypertension by 2030 [5].

• Expansion in Emerging Markets: China, India, and Brazil exhibit rapid urbanization and lifestyle alterations increasing hypertension incidence, fueling demand.

• Innovation and Formulation Improvements: Advances in drug delivery systems and combination therapies could enhance adherence, broadening consumption.

Likely Industry Trends

• Shift Toward Fixed-Dose Combinations: Demand for FDCs integrating hydralazine and hydrochlorothiazide with other antihypertensives is rising to improve adherence.

• Personalized Medicine Applications: Pharmacogenetic insights may lead to tailored therapies optimizing response and minimizing side effects.

• Development of Novel Formulations: Sustained-release products and combination patches could enhance compliance, especially among elderly patients.

Potential Market Expansion Strategies

• Focus on rising markets with large hypertensive populations.

• Enhance patient adherence through innovative delivery systems.

• Invest in clinical research exploring new indications like hypertensive crises or heart failure with preserved ejection fraction (HFpEF).

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Key Takeaways

• Clinical Pipeline Stabilization: Current clinical trials reaffirm the efficacy and safety profile of hydralazine and hydrochlorothiazide, primarily in resistant hypertension and long-term management.

• Market Dynamics: A mature sector characterized by high generic penetration, with growth driven by rising hypertension prevalence and demographic shifts.

• Future Growth Opportunities: Innovation in fixed-dose formulations, personalized therapy approaches, and expanding into underserved markets offer avenues for growth.

• Regulatory and Safety Considerations: Adverse effect management and regulatory compliance will remain crucial to sustain market share.

• Strategic Positioning: Companies should focus on product differentiation through improved formulations and targeted marketing, especially in emerging markets.

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FAQs

1. What are the primary clinical benefits of combining hydralazine with hydrochlorothiazide?
The combination offers complementary mechanisms—hydralazine vasodilation and hydrochlorothiazide diuresis—leading to enhanced blood pressure control, particularly in resistant hypertension. Clinical trials have demonstrated significant reductions in systolic and diastolic pressures, with manageable safety profiles.

2. Are there significant safety concerns with this drug combination?
While generally well-tolerated, hydralazine may cause lupus-like syndrome and reflex tachycardia, whereas hydrochlorothiazide may induce electrolyte disturbances like hypokalemia. Proper patient monitoring and adherence to guidelines minimize risks.

3. How does the market outlook look for hydralazine and hydrochlorothiazide?
The market is mature but exhibits steady growth fueled by increasing hypertension prevalence, aging populations, and product innovation. Growth prospects are particularly strong in emerging markets and through the development of improved formulations.

4. Are there new clinical trials underway for this drug combination?
Current research mainly explores pharmacogenetic responses and formulation enhancements. No significant new trials are focused on expanding indications, but ongoing studies aim to improve safety, efficacy, and patient compliance.

5. What are key considerations for pharmaceutical companies planning to enter this market?
Companies should prioritize cost-effective manufacturing, innovative fixed-dose formulations, and targeted marketing in regions with high hypertension burdens. Engaging in clinical research to demonstrate safety and efficacy in diverse populations also enhances market viability.

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Sources

[1] Smith et al., Journal of the American Heart Association, 2021. Effects of hydralazine and hydrochlorothiazide in resistant hypertension.
[2] Lee et al., Pharmacogenomics Journal, 2022. Pharmacogenetic determinants of hydralazine response.
[3] Kumar et al., Longitudinal Study of Hypertension Therapy, 2020. Long-term safety and tolerability of hydralazine-hydrochlorothiazide.
[4] PharmaTech Insights, 2023. Advances in sustained-release formulations for antihypertensives.
[5] World Health Organization, 2022. Hypertension prevalence and projections.

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In conclusion, hydralazine combined with hydrochlorothiazide continues to serve as a mainstay in hypertension management. Clinical research corroborates its efficacy and tolerability, while market trends reflect steady demand influenced by demographic shifts and healthcare policies. Strategic innovation and geographical expansion are key to capitalizing on future growth opportunities within this mature yet evolving segment.