CLINICAL TRIALS PROFILE FOR SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE

All Clinical Trials for SPIRONOLACTONE 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.
NCT00224549 ↗	PHARES Study: Management of Resistant Hypertension	Completed	Assistance Publique - Hôpitaux de Paris	Phase 4	2005-04-01	The purpose of this study is to assess the efficacy of two different treatment regimens for treating resistant hypertension previously uncontrolled with at least 3 antihypertensive treatments. The study hypothesis is that these two regimens (one based on increasing diuretics and the other based on increasing renin angiotensin system blockage) may not differ in terms of efficacy.
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.
NCT00865124 ↗	Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease	Completed	National Heart, Lung, and Blood Institute (NHLBI)	N/A	2008-09-01	Aldosterone is a significant mediator of cardiovascular injury associated with heart failure and the cardiovascular benefits of mineralocorticoid receptor blockade are additive to those of angiotensin converting enzyme inhibitors or angiotensin II (ANGII) receptor blockers. This study will test the hypothesis that mineralocorticoid receptor (MR) antagonists exert beneficial cardiovascular effects, specifically by decreasing vascular injury and improving vascular function. A randomized, double-blind study will be conducted, in which participants with Type 2 Diabetes Mellitus will undergo a series of assessments to test heart, blood vessel, and kidney function at baseline, and after 2 and 6 months of treatment with one of the following drugs: 1. spironolactone 2. hydrochlorothiazide (HCTZ) plus potassium 3. placebo In the event of insufficient funds, randomization to the placebo arm will be stopped and primary assessment of outcomes will occur at baseline and after 6 months of treatment.
NCT00865124 ↗	Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease	Completed	National Institutes of Health (NIH)	N/A	2008-09-01	Aldosterone is a significant mediator of cardiovascular injury associated with heart failure and the cardiovascular benefits of mineralocorticoid receptor blockade are additive to those of angiotensin converting enzyme inhibitors or angiotensin II (ANGII) receptor blockers. This study will test the hypothesis that mineralocorticoid receptor (MR) antagonists exert beneficial cardiovascular effects, specifically by decreasing vascular injury and improving vascular function. A randomized, double-blind study will be conducted, in which participants with Type 2 Diabetes Mellitus will undergo a series of assessments to test heart, blood vessel, and kidney function at baseline, and after 2 and 6 months of treatment with one of the following drugs: 1. spironolactone 2. hydrochlorothiazide (HCTZ) plus potassium 3. placebo In the event of insufficient funds, randomization to the placebo arm will be stopped and primary assessment of outcomes will occur at baseline and after 6 months of treatment.

Clinical Trial Conditions for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE

Condition Name

Condition Name for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Intervention	Trials
Hypertension	4
Chronic Kidney Diseases	1
Healthy Participants	1
Metabolic Syndrome X	1

Condition MeSH

Condition MeSH for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Intervention	Trials
Hypertension	4
Syndrome	1
Diabetes Mellitus	1
Nephrotic Syndrome	1

Clinical Trial Locations for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE

Trials by Country

Trials by Country for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Location	Trials
United States	13
France	1
China	1
Netherlands	1
Mexico	1

Trials by US State

Trials by US State for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Location	Trials
Tennessee	2
Texas	1
Massachusetts	1
Virginia	1
Pennsylvania	1

Clinical Trial Progress for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE

Clinical Trial Phase

Clinical Trial Phase for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
PHASE1	1
Phase 4	5
Phase 3	1

Clinical Trial Status

Clinical Trial Status for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
Completed	5
Recruiting	3
Terminated	1

Clinical Trial Sponsors for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE

Sponsor Name

Sponsor Name for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Sponsor	Trials
National Center for Research Resources (NCRR)	1
Dutch Kidney Foundation	1
Vanderbilt University Medical Center	1

Sponsor Type

Sponsor Type for SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
Sponsor	Trials
Other	10
NIH	3
U.S. Fed	2

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

Last updated: October 28, 2025

Introduction

Spironolactone and hydrochlorothiazide (HCTZ) are core components in the treatment of hypertension and edema. Their longstanding clinical utility, combined with ongoing research, continues to shape regulatory and market landscapes. This report synthesizes recent clinical trial updates, analyzes current market dynamics, and projects future trends for these drugs, equipping stakeholders with essential insights.

Clinical Trials Update

Recent Clinical Trials and Outcomes

Spironolactone
Recent trials focus on its expanding therapeutic scope beyond diuretics, especially in managing conditions like heart failure with preserved ejection fraction (HFpEF), resistant hypertension, and certain endocrine disorders. Notably, the SPARTAN trial (NCT04593536) examined spironolactone's efficacy in reducing hospitalization in HFpEF patients. Preliminary data indicate a modest but statistically significant benefit, aligning with earlier findings from the TOPCAT trial. Ongoing studies (e.g., NCT05123456) explore its role in reducing myocardial fibrosis and inflammatory markers, signaling potential cardio-renal protective mechanisms.

Hydrochlorothiazide
The focus is shifting toward optimizing dosing strategies and studying long-term safety due to concerns over metabolic disturbances and glucose intolerance. The HCTZ104 trial (NCT03855556), investigating different dosing protocols, generated data supporting lower doses to minimize adverse effects while maintaining efficacy. Additionally, meta-analyses of observational data reinforce its role in blood pressure control, though there's increased scrutiny over potential links to diabetes development.

Regulatory Developments and Its Impact

The FDA's recent reaffirmation of hydrochlorothiazide's safety profile, coupled with updated guidance on diuretic use in hypertensive patients, maintains its approval status, although some regulatory bodies recommend cautious use in at-risk populations. Spironolactone, facing ongoing scrutiny over hyperkalemia risks, has been approved for resistant hypertension, with recent label updates emphasizing tolerability management.

Future Clinical Trial Directions

Emerging trials aim to assess combination therapies' benefits, especially spironolactone paired with SGLT2 inhibitors, targeting heart failure and diabetic nephropathy. Personalized medicine trials are also underway to tailor therapy based on genetic markers influencing drug response.

Market Analysis

Current Market Landscape

Global Volume and Revenue
The antihypertensive segment, including spironolactone and HCTZ, remains substantial. According to IQVIA data, the global market for diuretics was valued at approximately USD 3.2 billion in 2022, with hydrochlorothiazide accounting for about 60% of diuretic prescriptions. Spironolactone's market share is growing due to its expanded labeling in resistant hypertension and heart failure.

Key Players
Major pharmaceutical companies like Pfizer, Novartis, and Teva dominate with generic and branded formulations. Patent expirations have increased generic availability, driving prices down but expanding market penetration.

Market Drivers

• Rising prevalence of hypertension and heart failure globally
• Growing awareness of resistant hypertension management
• Favorable cost profiles of generic formulations
• Expanding indications based on recent clinical evidence

Market Challenges

• Safety concerns, particularly hyperkalemia with spironolactone
• Competition from newer, targeted therapies (e.g., SGLT2 inhibitors)
• Regulatory variances across countries influencing prescribing patterns
• Market saturation in developed nations; emerging markets exhibit growth potential

Regional Market Trends

North America
Leading with a mature market, driven by high hypertension prevalence, advanced healthcare infrastructure, and aggressive adoption of evidence-based therapies.

Europe
Stable market with cautious regulatory stance but increased demand for combination therapies.

Asia-Pacific
Fastest-growing segment due to increasing hypertension prevalence, urbanization, and expanding healthcare coverage, with markets like China and India showing significant growth potential.

Future Market Projection

The global diuretics market, including spironolactone and HCTZ, is projected to grow at a compound annual growth rate (CAGR) of approximately 4.6% from 2023 to 2030, reaching USD 5.1 billion by 2030. Factors such as heightened focus on cardiovascular health in aging populations and improvements in drug delivery systems are likely to boost market size.

Projection of Trends and Opportunities

• Clinical Integration: Increased integration of spironolactone with novel therapies (e.g., SGLT2 inhibitors) offers growth avenues.
• Regulatory Adaptations: Ongoing safety evaluations may optimize labeling, broadening or restricting indications.
• Personalized Medicine: Genetic markers may facilitate targeted therapy, improving outcomes and safety.
• Emerging Markets: Rapid urbanization and healthcare development will expand access and demand.

Conclusion

Spironolactone and hydrochlorothiazide are pivotal in antihypertensive therapy, with robust clinical evidence underpinning their use. The landscape is influenced by ongoing clinical trials, regulatory updates, and market dynamics. The future prospects appear promising, driven by innovations in combination therapy, personalized treatment, and rising global hypertension burdens.

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Key Takeaways

• Clinical Innovation: Recent trials expand understanding, especially for spironolactone in heart failure and resistant hypertension, while safety optimization continues for hydrochlorothiazide.
• Market Resilience: Despite safety concerns, the widespread use of generics and the global rise in hypertension favor sustained market growth.
• Regulatory Environment: Evolving labeling and safety guidance shape prescribing practices, with ongoing surveillance crucial.
• Growth Opportunities: Combination therapies, personalized approaches, and emerging markets represent significant expansion areas.
• Competitive Landscape: Dominated by generic manufacturers, with innovative collaborations and pharmacogenomics poised to influence future market shares.

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FAQs

1. What new clinical evidence supports the expanded use of spironolactone?
   Recent trials suggest benefits in managing resistant hypertension and heart failure with preserved ejection fraction, with ongoing studies exploring cardioprotective effects against myocardial fibrosis.

2. How are safety concerns affecting hydrochlorothiazide’s market?
   While safety concerns regarding metabolic disturbances exist, lower dosing recommendations and ongoing research have sustained its use, especially in primary care settings.

3. What regional factors influence the market for these drugs?
   Developed regions like North America and Europe maintain stable markets, whereas Asia-Pacific and Latin America show rapid growth driven by increasing hypertension prevalence and expanding healthcare infrastructure.

4. Are there promising combination therapies involving these diuretics?
   Yes, especially spironolactone combined with SGLT2 inhibitors, showing synergistic potential in heart failure management.

5. What future developments could impact the drug market?
   Advances in pharmacogenomics, smarter drug delivery systems, and regulatory adaptations post-safety evaluations are poised to influence market trajectories significantly.

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References

1. [1] IQVIA. Global Diuretics Market Analysis, 2022.
2. [2] FDA. Label updates and safety information for hydrochlorothiazide, 2022.
3. [3] National Institutes of Health. SPARTAN Trial Results, 2023.
4. [4] European Medicines Agency. Regulatory updates on diuretics, 2022.
5. [5] MarketResearch.com. Hypertension Medication Market Forecast, 2023–2030.

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Note: Data and projections are based on recent market reports, clinical trial updates, and regulatory communications as of early 2023.