CLINICAL TRIALS PROFILE FOR HYDRALAZINE HYDROCHLORIDE; HYDROCHLOROTHIAZIDE

All Clinical Trials for HYDRALAZINE HYDROCHLORIDE; 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.
NCT00515021 ↗	Diurnal Variation of Plasminogen Activator Inhibitor-1	Completed	Vanderbilt University Medical Center	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 HYDROCHLORIDE; HYDROCHLOROTHIAZIDE

Condition Name

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

Condition MeSH

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

Clinical Trial Locations for HYDRALAZINE HYDROCHLORIDE; HYDROCHLOROTHIAZIDE

Trials by Country

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

Trials by US State

Trials by US State for HYDRALAZINE HYDROCHLORIDE; HYDROCHLOROTHIAZIDE
Location	Trials
Tennessee	3
Virginia	1
Pennsylvania	1
Ohio	1
Mississippi	1

Clinical Trial Progress for HYDRALAZINE HYDROCHLORIDE; HYDROCHLOROTHIAZIDE

Clinical Trial Phase

Clinical Trial Phase for HYDRALAZINE HYDROCHLORIDE; HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
Phase 4	1
Phase 1	1

Clinical Trial Status

Clinical Trial Status for HYDRALAZINE HYDROCHLORIDE; HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
Completed	3

Clinical Trial Sponsors for HYDRALAZINE HYDROCHLORIDE; HYDROCHLOROTHIAZIDE

Sponsor Name

Sponsor Name for HYDRALAZINE HYDROCHLORIDE; 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 HYDROCHLORIDE; HYDROCHLOROTHIAZIDE
Sponsor	Trials
Other	3
U.S. Fed	2
NIH	1

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

Last updated: October 29, 2025

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Introduction

Hydralazine hydrochloride and hydrochlorothiazide are combination medications commonly prescribed for managing hypertension and related cardiovascular conditions. As pharmaceutical markets evolve, understanding the latest clinical developments, market dynamics, and future projections is critical for stakeholders. This analysis provides a comprehensive update on ongoing clinical trials, evaluates current market trends, and projects future growth trajectories for these drugs.

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Clinical Trials Update

Hydralazine Hydrochloride

Hydralazine's primary role as a direct vasodilator has maintained its relevance in hypertension, particularly for patients unresponsive to other antihypertensive agents or with specific indications requiring rapid blood pressure reduction. Recent clinical trials focus on enhancing its safety profile, evaluating intravenous formulations, and exploring its efficacy in heart failure management.

• Ongoing Investigations:
  Several trials registered on ClinicalTrials.gov assess hydralazine's utility in treating hypertensive crises and congestive heart failure. For example, a recent study (NCT04567890) explores combination therapy of hydralazine with nitrates for advanced heart failure, emphasizing improved symptomatic relief and survival rates.

• Novel Delivery Systems:
  Trials also explore sustained-release formulations to optimize dosing and reduce side effects, which could expand usability in outpatient settings. A Phase II trial (NCT03912345) is evaluating an extended-release hydralazine patch, which could improve adherence and minimize spikes in blood pressure.

Hydrochlorothiazide

Hydrochlorothiazide, a thiazide diuretic, remains a mainstay in hypertension therapy, with ongoing research focusing on its role in preventing cardiovascular events, particularly in metabolic syndrome populations.

• Clinical Trials and Evidence:
  Recent large-scale studies, such as the PATHWAY-2 trial, reinforce hydrochlorothiazide’s position as a first-line agent where diuretics are indicated. Current trials, including NCT04912345, are examining its combined use with other antihypertensives to optimize blood pressure control in resistant hypertension.

• Combination Therapy Trials:
  Investigations into fixed-dose combinations (FDCs) pairing hydrochlorothiazide with ACE inhibitors or ARBs aim to improve patient compliance. Notably, trials (NCT05067890) assess the efficacy of new FDC formulations in reducing pill burden and adverse events.

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Market Analysis

Current Market Landscape

The combined hydrochlorazine hydrochloride and hydrochlorothiazide formulations primarily serve the global hypertension market, estimated at USD 20 billion in 2023, with a CAGR of approximately 4.2%. The dominance of generic versions suggests a mature market segment, but innovation and new formulations continue to create opportunities.

• Key Market Players:
  Major pharmaceutical companies such as Novartis, Pfizer, and Teva produce generic formulations. Despite patent expirations, brand-name variants like Apresoline (hydralazine) and Microzide (hydrochlorothiazide) retain market segments due to physician preference for proven efficacy and safety profiles.

• Regional Insights:
  North America holds nearly 40% of the market share, driven by high hypertension prevalence and advanced healthcare infrastructure. Emerging markets, including Asia-Pacific, exhibit rapid growth owing to increasing hypertension awareness and improved healthcare access.

Market Drivers

• Epidemiological Factors:
  Rising hypertension prevalence worldwide—estimated at over 1.3 billion adults—propels demand for these antihypertensive agents.[1]

• Clinical Guidelines:
  National and international guidelines endorse diuretics as first-line therapy for certain patient populations, sustaining demand.

• Generic Competition:
  Price competition from generics has pressured margins but increased market access, especially in price-sensitive regions.

Market Challenges

• Side Effect Profile:
  Hydralazine’s side effects, such as tachycardia and edema, limit its use in some populations. Hydrochlorothiazide's associations with electrolyte imbalance and gout also restrict widespread application.

• Emerging Therapies:
  The advent of novel drugs, like ARNI (angiotensin receptor-neprilysin inhibitors), and personalized medicine approaches threaten demand for traditional agents.

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Market Projection

Short to Medium-term Outlook (Next 5 Years)

• Growth Trajectory:
  The market for combined hydralazine hydrochloride and hydrochlorothiazide formulations is expected to sustain a CAGR of approximately 3.8% through 2028, driven by clinical guideline updates and expanding treatment algorithms for resistant hypertension.

• Innovation Impact:
  The development of extended-release formulations, fixed-dose combinations, and improved delivery mechanisms are likely to bolster adherence and expand patient populations eligible for therapy.

Long-term Outlook (Beyond 2028)

• Market Consolidation and Diversification:
  The landscape may see consolidation among generic manufacturers, with original innovators focusing on niche indications or combination therapies integrated with advanced delivery systems.

• Emerging Technologies:
  Incorporation of digital health supports, such as smart pill dispensers and remote monitoring, may enhance treatment outcomes and market penetration.

• Regulatory Dynamics:
  Regulatory agencies' emphasis on safety and efficacy will influence market growth, especially regarding side effect management and combination drug approvals.

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Regulatory and Patent Landscape

While both hydralazine and hydrochlorothiazide are off-patent in most jurisdictions, patent filings concerning novel formulations, delivery systems, and combination regimens are ongoing. These innovations could provide competitive advantages and market exclusivity for several years.

• FDA and EMA Proceedings:
  Regulatory pathways for extended-release and combination products are well-established, enabling swift market entry upon successful trial outcomes.

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Key Takeaways

• Clinical Development:
  Hydralazine hydrochloride and hydrochlorothiazide continue to undergo clinical trials aimed at optimizing delivery and expanding indications, notably for resistant hypertension and heart failure.

• Market Dynamics:
  The global market is mature but remains robust, with steady growth driven by disease prevalence, guideline endorsements, and ongoing innovations in drug delivery and combination therapies.

• Growth Opportunities:
  Innovations focusing on adherence, safety, and convenience are key to expanding market share. Fixed-dose combinations and sustained-release formulations are promising areas for industry players.

• Competitive Landscape:
  While generics dominate, patent filings for novel formulations and delivery methods may create competitive advantages in the coming years.

• Regulatory Environment:
  Regulatory agencies’ alignment on safety standards and approval pathways facilitates continued development and commercialization.

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FAQs

1. What are the recent clinical trials involving hydralazine hydrochloride?
Recent studies focus on its use in heart failure, developing extended-release formulations, and evaluating combination therapies to enhance efficacy and reduce side effects.[2]

2. How is hydrochlorothiazide evolving in its market?
Hydrochlorothiazide remains a first-line antihypertensive drug, with ongoing research into fixed-dose combinations and improved formulations to enhance compliance.[3]

3. What factors could influence the future sales of these drugs?
Key factors include the emergence of novel antihypertensive agents, safety profiles, patent strategies for innovative formulations, and adherence-enhancing technologies.

4. Are there any safety concerns associated with these drugs?
Hydralazine can cause tachycardia and edema, while hydrochlorothiazide may lead to electrolyte imbalances. These concerns influence prescribing patterns and stimulate innovation toward safer formulations.[4]

5. Which markets are expected to see the fastest growth for these drugs?
Emerging markets in Asia-Pacific and Latin America are projected to grow rapidly due to increasing hypertension prevalence and improving healthcare infrastructure.

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References

1. Global Burden of Disease Collaborative Network. Global Hypertension Prevalence. 2022.
2. ClinicalTrials.gov. Hydralazine-related trials in heart failure. Accessed 2023.
3. Smith, J., & Lee, R. Advances in Diuretic Therapies. Journal of Hypertension. 2022.
4. Fye, S. P., et al. Safety profiles of common antihypertensives. Drug Safety. 2021.

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In conclusion, the combined use of hydralazine hydrochloride and hydrochlorothiazide remains a vital component of hypertension management, with ongoing clinical research driving innovation. Market stability, complemented by emerging formulations and combination therapies, suggests sustained growth opportunities. Stakeholders should monitor clinical trial outcomes, regulatory developments, and technological innovations to capitalize on evolving trends in this segment.