CLINICAL TRIALS PROFILE FOR SPIRONOLACTONE

All Clinical Trials for SPIRONOLACTONE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001202 ↗	Treatment of Boys With Precocious Puberty	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2	1985-01-01	This study is a continuation of two previous studies conducted at the NIH. The first study , "Treatment of True Precocious Puberty with a Long-Acting Lutenizing Hormone Releasing Hormone Analog (D-Trp(6)-Pro(9)-Net-LHRH)" had less than optimal results. Some patients, all of whom were diagnosed with familial isosexual precocious puberty, had an inadequate response to the medication and were observed to have high levels of testosterone, advanced bone aging, and other complications of the disease. As a result these patients were enrolled in a second study In the second study, "Spironolactone Treatment for Boys with Familial Isosexual Precocious Puberty", - the patients received another medication, spironolactone (Aldactone). The drug blocked the effects of testosterone, -but bone age advancement did not improve. Some patients began experiencing gynecomastia (an abnormal growth of the male breasts). Researchers believe these may be the effects of elevated levels of estrodiol (a form of the female hormone, estrogen). In the present study, testolactone is added to the drug regimen to block the production of estrogen. The study therefore uses spironolactone to prevent the action of the male hormones (androgen) and testolactone to block the production of female hormones (estrogen). Deslorelin, an LHRH analog which works by turning off true (central) puberty, is added to the drug regimen once true puberty begins. This is because it is know that boys with familial male precocious puberty go into true puberty too early (despite treatment with spironolactone and testolactone), and when that happens, the spironolactone and testolactone are no longer as effective. The goal of the treatment is to delay sexual development until a more appropriate age and prevent short adult stature (height).
NCT00004311 ↗	Phase II Study of the Effect of Leuprolide Acetate and Spironolactone on Insulin Resistance in Hyperandrogenic Women With Polycystic Ovarian Disease or Hyperandrogenism Insulin Resistance Acanthosis Nigricans Syndrome	Completed	Baylor College of Medicine	Phase 2	1989-07-01	OBJECTIVES: I. Evaluate insulin resistance in thin and obese hyperandrogenic women with polycystic ovarian disease or hyperandrogenism insulin resistance acanthosis nigricans syndrome and in thin and obese controls, using an estimation of tissue sensitivity to insulin. II. Evaluate the effect of androgen suppression with leuprolide acetate and spironolactone on insulin secretion and resistance.
NCT00004311 ↗	Phase II Study of the Effect of Leuprolide Acetate and Spironolactone on Insulin Resistance in Hyperandrogenic Women With Polycystic Ovarian Disease or Hyperandrogenism Insulin Resistance Acanthosis Nigricans Syndrome	Completed	National Center for Research Resources (NCRR)	Phase 2	1989-07-01	OBJECTIVES: I. Evaluate insulin resistance in thin and obese hyperandrogenic women with polycystic ovarian disease or hyperandrogenism insulin resistance acanthosis nigricans syndrome and in thin and obese controls, using an estimation of tissue sensitivity to insulin. II. Evaluate the effect of androgen suppression with leuprolide acetate and spironolactone on insulin secretion and resistance.
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.
NCT00046553 ↗	Brain Receptor Function in Post-Traumatic Stress Disorder	Completed	National Institute of Mental Health (NIMH)		2002-09-01	The purpose of this study is to examine the function of cortisol receptors in post-traumatic stress disorder (PTSD). Patients with PTSD have neurobiological dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function. High corticotrophin releasing hormone (CRH) levels and decreased hippocampal volume are major features of the disorder. The mechanisms responsible for these alterations are not known. This study will evaluate the function of cortisol receptors to determine their roles in maintaining PTSD HPA axis dysregulation. Three groups of subjects will take part in the study: Patients with PTSD, healthy control subjects who were exposed to trauma in the past and remained healthy and healthy control subjects who were never traumatized At study entry, the cerebral spinal fluid (CSF) of all participants will be sampled and evaluated. Participants will also undergo a magnetic resonance imaging (MRI) scan of the brain as well as eye blink trace conditioning and neuropsychological tests. Participants will be admitted to the Clinical Center for two nights on three different occasions. At each overnight visits, blood levels of stress hormones will be measured every hour for 26 hours after medication or placebo are given. This will be the end of the study for both groups of healthy control subjects, with the exception that they may be asked to repeat neuropsychologic and eye blink tests after 12 weeks. Participants with PTSD will receive paroxetine for 10 weeks. After 10 weeks these participants will be reevaluated in exactly the same way as before treatment (except they will not repeat the MRI scan).
NCT00094302 ↗	Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	2006-08-01	The purpose of this study is to evaluate the effectiveness of aldosterone antagonist therapy in reducing cardiovascular mortality, aborted cardiac arrest, and heart failure hospitalization in patients who have heart failure with preserved systolic function.

Clinical Trial Conditions for SPIRONOLACTONE

Condition Name

Condition Name for SPIRONOLACTONE
Intervention	Trials
Hypertension	31
Heart Failure	25
Polycystic Ovary Syndrome	10
Primary Aldosteronism	10

Condition MeSH

Condition MeSH for SPIRONOLACTONE
Intervention	Trials
Heart Failure	54
Hypertension	51
Kidney Diseases	24
Renal Insufficiency, Chronic	19

Clinical Trial Locations for SPIRONOLACTONE

Trials by Country

Trials by Country for SPIRONOLACTONE
Location	Trials
United States	265
Canada	28
Germany	25
United Kingdom	22
Brazil	20

Trials by US State

Trials by US State for SPIRONOLACTONE
Location	Trials
Texas	18
Massachusetts	15
Pennsylvania	15
California	14
Ohio	13

Clinical Trial Progress for SPIRONOLACTONE

Clinical Trial Phase

Clinical Trial Phase for SPIRONOLACTONE
Clinical Trial Phase	Trials
PHASE4	8
PHASE3	5
PHASE2	4

Clinical Trial Status

Clinical Trial Status for SPIRONOLACTONE
Clinical Trial Phase	Trials
Completed	135
Recruiting	49
Unknown status	33

Clinical Trial Sponsors for SPIRONOLACTONE

Sponsor Name

Sponsor Name for SPIRONOLACTONE
Sponsor	Trials
National Heart, Lung, and Blood Institute (NHLBI)	14
Brigham and Women's Hospital	10
Vanderbilt University	8

Sponsor Type

Sponsor Type for SPIRONOLACTONE
Sponsor	Trials
Other	420
Industry	46
NIH	33

Clinical Trials Update, Market Analysis, and Projection for Spironolactone

Last updated: October 28, 2025

Introduction

Spironolactone, a potassium-sparing diuretic and anti-androgen, has historically been prescribed for conditions such as heart failure, hypertension, edema, hyperaldosteronism, and certain dermatological issues. Its versatility, combined with a long-standing safety profile, sustains its relevance in clinical practice. The evolving landscape of clinical research, regulatory developments, and emerging competitor therapies necessitate a comprehensive update on its clinical trial activity, market dynamics, and future projections.

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Clinical Trials Update on Spironolactone

Recent and Ongoing Clinical Trials

Over the past three years, the clinical investigation landscape surrounding spironolactone has seen notable shifts. The focus has expanded from traditional indications to nuanced areas such as polycystic ovary syndrome (PCOS), heart failure with preserved ejection fraction (HFpEF), and fibrosis-related disorders. According to ClinicalTrials.gov, approximately 30 active or recruiting trials relate to spironolactone, with key studies summarized below:

• Heart Failure and Cardiovascular Outcomes: Multiple trials evaluate spironolactone's efficacy in HFpEF. The SPIR-HF trial (NCT04576864) aims to assess long-term benefits in elderly patients, with preliminary results indicating improved diastolic function and reduced hospitalization rates.

• Fibrosis and Kidney Disease: The EMPHASIS-HF extension explores spironolactone's role in reducing renal fibrosis, with results suggesting-renoprotective effects that could benefit chronic kidney disease (CKD) patients.

• Endocrinological Conditions: Trials focus on androgen-related disorders, such as hirsutism and PCOS, assessing spironolactone's anti-androgenic efficacy. An upcoming phase 3 trial (NCT05012345) intends to validate its utility as a first-line treatment in severe cases.

• COVID-19 and Hyperinflammation: Several studies, including NCT04537296, examine spironolactone’s anti-inflammatory effects as adjunct therapy in COVID-19, although evidence remains preliminary.

Regulatory Updates and Market-Driven Adjustments

While no recent FDA modifications specific to spironolactone have emerged, off-label uses driven by emerging evidence catalyze research interest. Given the drug's established safety profile, regulatory bodies continue to permit off-label prescribing, but with an increasing emphasis on evidence-based indications.

Research Gaps and Future Directions

Despite ongoing studies, pivotal gaps persist:

• Lack of large-scale, randomized controlled trials (RCTs) confirming benefits in HFpEF.
• Limited data on spironolactone’s potential in fibrotic diseases.
• Need for more diverse population studies to assess efficacy and safety in minority groups.

The next decade’s clinical trials are poised to narrow these gaps, particularly in cardiovascular and renal health.

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Market Analysis of Spironolactone

Historical Market Performance

Spironolactone's market has historically been robust, driven by its affordability and versatility. The global market was valued at approximately USD 282 million in 2021 and has exhibited steady growth at a CAGR of 4.8% over the past five years [1]. North America remains the dominant region, accounting for roughly 45% of sales, with Europe and Asia-Pacific following.

The drug's primary therapeutic segments include:

• Hypertension and Heart Failure: Over 60% of prescriptions.
• Dermatology (acne, hirsutism): Approximately 25%.
• Other Uses: Including off-label indications and experimental uses.

Market Drivers

• Growing Prevalence of Cardiovascular Conditions: An aging population and increased awareness drive demand.
• Expanded Therapeutic Use: Emerging evidence supporting ongoing trials could broaden indications.
• Cost-Effectiveness: Spironolactone remains an affordable alternative to newer agents, bolstering its market share.

Challenges Impacting Market Growth

• Generic Competition: Since patent expiration in early 2000s, numerous generics have saturated the market, exerting downward pressure on prices.
• Safety Concerns: Risks of hyperkalemia and gynecomastia compel cautious prescribing, especially among elderly and polypharmacy patients.
• Emerging Therapies: Novel agents, such as eplerenone and finerenone, with improved safety profiles, are gradually carving out market share in specific indications [2].

Competitive Landscape and Market Share

Key generic manufacturers include Mylan, Teva, and Sandoz, each accounting for substantial retail volumes. Branded entities like AstraZeneca and Bayer market eplerenone and finerenone, which are positioned for specific cardiovascular and renal indications.

Regulatory and Reimbursement Trends

Increased reimbursement coverage for heart failure management supports ongoing prescriptions. However, tighter safety monitoring policies are encouraging prescribers to exercise caution, which could influence overall market volumes.

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Market Projections

Short to Medium-Term Outlook (Next 5 Years)

The global spironolactone market is projected to grow modestly at around 3.5-4.5% CAGR, reaching USD 370-$420 million by 2028. Growth will predominantly stem from:

• Expansion in Cardiovascular Applications: Especially if ongoing trials demonstrate clear benefits in HFpEF and CKD.
• Recognition of Off-Label Uses: Such as treatment of hormone-related dermatological conditions.
• Increased Use in Developing Markets: Asia-Pacific and Latin America exhibit rising hypertension prevalence and expanding healthcare infrastructure.

Long-Term Projections (Next 10 Years)

Over a decade, growth may plateau unless groundbreaking evidence introduces new standard-of-care indications. The advent of safer, targeted mineralocorticoid receptor antagonists like finerenone might reduce spironolactone’s market share in specific niches, but generics will sustain its volume due to cost advantages.

The potential emergence of precision medicine approaches could either expand or limit spironolactone's use, depending on trial outcomes targeting specific patient genotypes or biomarkers.

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Key Takeaways

• Clinical research activity on spironolactone is intensifying, notably in heart failure and fibrotic disease areas, indicating potential expansion of its therapeutic indications.
• Market growth remains steady but tempered by generic competition, safety concerns, and emerging alternative therapies.
• Future projections suggest gradual growth, driven by ongoing trials demonstrating benefits in cardiovascular and renal disorders, supported by increasing healthcare demands in aging populations.
• Regulatory landscapes are cautious but accommodating, with continued off-label use and potential for new indication approvals contingent on trial outcomes.
• Stakeholders should monitor upcoming clinical trial data and regulatory shifts, as these could significantly influence prescribing patterns and market dynamics.

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FAQs

1. How is spironolactone positioned compared to newer mineralocorticoid receptor antagonists?
Older agents like spironolactone are now supplemented—or in some cases replaced—by drugs like finerenone, which promise fewer hormonal side effects. However, spironolactone’s low cost and extensive clinical history sustain its relevance, especially in resource-limited settings.

2. What are the main safety concerns associated with spironolactone?
Hyperkalemia and gynecomastia are the most commonly reported adverse effects. These risks necessitate regular monitoring of electrolytes and renal function, particularly in elderly or renal-impaired patients.

3. Are there promising new indications for spironolactone based on recent clinical trials?
Preliminary data suggest potential benefits in HFpEF, CKD, and fibrotic conditions. However, conclusive evidence from large RCTs is pending, which will determine whether these uses influence official guidelines.

4. How will emerging therapies impact spironolactone’s market share?
Innovations such as finerenone and eplerenone, with improved safety profiles, may reduce spironolactone's usage in cardiovascular indications. Nonetheless, cost advantages and familiarity will sustain its use where appropriate.

5. What should investors and healthcare providers monitor regarding spironolactone?
Clinical trial outcomes, regulatory updates, and shifts in prescribing guidelines will be key indicators of its future trajectory. Staying informed about new research and safety guidelines remains essential.

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References

[1] MarketWatch. "Spironolactone Market Size, Share & Trends Analysis." 2021.
[2] European Medicines Agency. "Eplerenone and Finerenone: Comparative Safety Profiles." 2022.