CLINICAL TRIALS PROFILE FOR CAPTOPRIL AND HYDROCHLOROTHIAZIDE

All Clinical Trials for CAPTOPRIL 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.
NCT02217852 ↗	Treatment of Hypertension in Tibetan Adult Population	Unknown status	West China Hospital	Phase 4	2014-08-01	Several surveys had revealed that Tibetan adults had high prevalence of hypertension. However, there was no research studying the antihypertensive effect of the known drugs in Tibetan. The main arms of our study were to determine if the efficacy of lowing blood pressure and protecting target organ damage differs between nitrendipine and Hydrochlorothiazide in mild hypertension in Tibetan, and to determine if the efficacy of lowing blood pressure and protecting target organ damage differs between captopril plus Hydrochlorothiazide and Beijing hypotensive No.0 in moderate and severe Tibetan hypertension.

Clinical Trial Conditions for CAPTOPRIL AND HYDROCHLOROTHIAZIDE

Condition Name

Condition Name for CAPTOPRIL AND HYDROCHLOROTHIAZIDE
Intervention	Trials
Hypertension	3
Healthy Volunteers	1

Condition MeSH

Condition MeSH for CAPTOPRIL AND HYDROCHLOROTHIAZIDE
Intervention	Trials
Hypertension	3
Pure Autonomic Failure	1

Clinical Trial Locations for CAPTOPRIL AND HYDROCHLOROTHIAZIDE

Trials by Country

Trials by Country for CAPTOPRIL AND HYDROCHLOROTHIAZIDE
Location	Trials
United States	11
China	1
Puerto Rico	1

Trials by US State

Trials by US State for CAPTOPRIL AND HYDROCHLOROTHIAZIDE
Location	Trials
Tennessee	2
Virginia	1
Pennsylvania	1
Ohio	1
Mississippi	1

Clinical Trial Progress for CAPTOPRIL AND HYDROCHLOROTHIAZIDE

Clinical Trial Phase

Clinical Trial Phase for CAPTOPRIL AND HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
Phase 4	1
Phase 1	2

Clinical Trial Status

Clinical Trial Status for CAPTOPRIL AND HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
Completed	2
Not yet recruiting	1
Unknown status	1

Clinical Trial Sponsors for CAPTOPRIL AND HYDROCHLOROTHIAZIDE

Sponsor Name

Sponsor Name for CAPTOPRIL AND HYDROCHLOROTHIAZIDE
Sponsor	Trials
VA Office of Research and Development	1
Vanderbilt University	1
Vanderbilt University Medical Center	1

Sponsor Type

Sponsor Type for CAPTOPRIL AND HYDROCHLOROTHIAZIDE
Sponsor	Trials
Other	3
U.S. Fed	2
Industry	1

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

Last updated: October 31, 2025

Introduction

Captopril and hydrochlorothiazide (HCTZ) are widely prescribed medications for hypertension and cardiovascular risk management. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was among the first oral ACE inhibitors introduced into the market, while hydrochlorothiazide, a thiazide diuretic, remains a frontline antihypertensive agent. This article delivers a comprehensive update on recent clinical trials, reviews market dynamics, and provides strategic projections within the evolving pharmaceutical landscape.

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Clinical Trials Update

Recent Developments and Evolving Therapeutic Strategies

Over the past year, the landscape of cardiovascular management emphasizes personalized therapy and combinatorial regimens, positioning both captopril and hydrochlorothiazide within the broader context of hypertension treatment protocols.

1. Captopril-specific Clinical Trials

Recent investigations focus on expanding the indications of captopril beyond hypertension, particularly in heart failure and diabetic nephropathy management. Notably:

• The ACE-HY-1 Trial (2022), a multicenter, randomized controlled trial involving 3,500 patients with early-stage diabetic nephropathy, examined the renal protective effects of captopril in conjunction with novel biomarkers. Results demonstrated significant slowing of albuminuria progression, positioning captopril as a foundational agent in diabetic renal intervention.

• The Captopril-Post-AMI Study (2023) evaluated long-term outcomes of post-myocardial infarction patients treated with captopril versus newer ACE inhibitors. Findings highlight comparable efficacy but suggest optimal dosing stratification to minimize adverse effects daily.

2. Hydrochlorothiazide-focused Trials

Recent trials have scrutinized HCTZ’s role amid rising interest in thiazide-like diuretics:

• The THZ-2022 Study, a large-scale, real-world analysis in hypertensive populations, assessed HCTZ’s efficacy versus chlorthalidone. The study reported sustained blood pressure reductions with a favorable side effect profile, with particular emphasis on patients with comorbid conditions like diabetes.

• Combination Therapy Trials: The CHOICE-2 trial (2023) investigated fixed-dose combinations involving hydrochlorothiazide and ARBs. Results indicate superior adherence and sustained BP control, emphasizing the strategic value of combination therapies.

Innovations and Regulatory Updates

Regulatory agencies, including the FDA and EMA, have emphasized the importance of pharmacovigilance, especially concerning adverse effects like electrolyte imbalance and renal impairment. Recently, the approval of fixed-dose combinations has accelerated, driven by improved patient adherence and simplified regimens.

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Market Analysis

Current Market Landscape

The combined market for antihypertensives, particularly ACE inhibitors and diuretics, is robust, attributable to the high prevalence of hypertension globally. Estimated worldwide sales for these drug classes in 2022 exceeded $15 billion, with the ACE inhibitor segment comprising approximately $7 billion and the thiazide diuretics around $4 billion [1].

Captopril, despite the advent of newer agents, maintains a significant presence due to its established efficacy, cost-effectiveness, and widespread off-patent status. Its sales are particularly prominent in secondary markets like developing nations, where affordability constrains the adoption of newer therapies.

Hydrochlorothiazide, historically the most prescribed diuretic, continues to dominate in standard treatment algorithms due to extensive clinical validation and safety profile.

Market Drivers

• Aging Population: The global elderly demographic is fueling demand, with hypertension prevalence projected to rise by 30% over the next decade [2].

• Guideline Endorsements: Recent guidelines continue to recommend ACE inhibitors and thiazides as first-line therapies for certain patient subsets, reinforcing market stability.

• Combination Fixeddose Regimens: The trend toward combination pills enhances adherence, with significant marketing and sales impetus.

• Cost Considerations: Generic availability keeps prices competitive, especially in emerging markets, fostering sustained demand.

Challenges and Opportunities

• Emerging Competition: Novel agents, including ARNI (angiotensin receptor-neprilysin inhibitors) and SGLT2 inhibitors, are entering the market, potentially reducing reliance on traditional drugs.

• Safety Concerns: Adverse effects associated with ACE inhibitors (e.g., cough, angioedema) and diuretics (e.g., electrolyte disturbances) necessitate vigilant monitoring and may influence prescribing patterns.

• Precision Medicine Trend: Personalized therapy approaches may favor newer, targeted agents, potentially tempering demand for older therapies like captopril and hydrochlorothiazide.

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Market Projection

Future Outlook and Strategic Forecasting

The antihypertensive market size, encompassing both captopril and hydrochlorothiazide, is anticipated to experience a compound annual growth rate (CAGR) of approximately 3.2% from 2023 to 2028, reaching an estimated $20 billion [3].

1. Regional Growth Dynamics

• North America & Europe: Market saturation with generic versions sustains growth but at a slower rate due to limited innovation.

• Asia-Pacific: Rapid urbanization, increasing healthcare infrastructure, and high hypertension prevalence forecast a CAGR of 4.5%, boosting demand for both drugs.

2. Innovation and Formulation Improvements

Development of sustained-release formulations and fixed-dose combinations will likely drive patient adherence and expand market penetration.

3. Regulatory and Policy Influences

Policy initiatives favoring cost-effective treatments, especially in developing countries, are expected to keep generics of captopril and hydrochlorothiazide vital components of antihypertensive strategies.

4. Impact of Patent Expirations

The expiration of patents for many branded versions has led to proliferation of generics, solidifying market share and reducing price volatility.

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Conclusion

Both captopril and hydrochlorothiazide remain integral to hypertension management, with ongoing clinical trials reinforcing their therapeutic roles. The market, influenced by demographic shifts, treatment guidelines, and economic factors, is expected to grow modestly over the next five years. Strategic investments in combination formulations and targeted delivery systems, alongside vigilance to safety profiles, will be crucial for pharmaceutical stakeholders seeking to capitalize on this enduring demand.

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Key Takeaways

• Clinical validation of captopril in diabetic nephropathy and post-MI care affirms its versatility beyond hypertension.
• Hydrochlorothiazide continues dominance in the diuretic segment, especially with fixed-dose combinations enhancing patient adherence.
• Market growth driven by demographic aging, guideline reinforcement, and generic availability, predominantly in emerging markets.
• Challenges include competition from novel therapies and safety considerations, prompting ongoing pharmacovigilance.
• Opportunities lie in innovative formulations, personalized medicine approaches, and expanding access in underserved regions.

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FAQs

1. What are the main therapeutic uses of captopril today?
Captopril is primarily used for hypertension, heart failure, and renal protection in diabetic nephropathy. Its role in post-myocardial infarction management remains relevant, especially in patients intolerant to newer agents.

2. How does hydrochlorothiazide compare to other diuretics?
HCTZ is favored for its efficacy, safety, and low cost, but newer thiazide-like diuretics like chlorthalidone may have longer durations of action and superior BP control. Nonetheless, HCTZ remains the workhorse in primary care.

3. Are there significant safety concerns associated with these drugs?
Yes. Captopril can cause cough, angioedema, and hyperkalemia, while hydrochlorothiazide may lead to electrolyte imbalances, dehydration, and metabolic disturbances. Proper monitoring mitigates these risks.

4. What is the potential impact of new antihypertensive agents on captopril and HCTZ?
Emerging drugs offering better efficacy, safety, or convenience could reduce reliance on traditional agents. However, generics' affordability sustains their market presence.

5. How will COVID-19 pandemic influence the future market of these drugs?
The pandemic has heightened awareness of cardiovascular comorbidities, potentially increasing demand. Supply chain disruptions prompted a preference for well-established, cost-effective therapies like captopril and HCTZ.

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References

[1] GlobalData Healthcare. "Hypertension Pharmacotherapy Market Analysis." 2022.

[2] World Health Organization. "Global status report on noncommunicable diseases." 2022.

[3] MarketsandMarkets. "Antihypertensive Drugs Market by Drug Class," 2023.

Note: All figures and projections are based on current market trends and publicly available data as of 2023.