CLINICAL TRIALS PROFILE FOR HYDROCHLOROTHIAZIDE; LISINOPRIL

All Clinical Trials for HYDROCHLOROTHIAZIDE; LISINOPRIL

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.
NCT00171535 ↗	Efficacy and Safety of Valsartan/Amlodipine Combination in Patients With Severe Hypertension	Completed	Novartis	Phase 3	2004-10-01	This study will assess the effectiveness and safety of different combination antihypertensive treatments in patients with severe hypertension
NCT00408512 ↗	Pharmacosurveillance and Pharmacogenetics of First-line Diuretics in Hypertension: The StayOnDiur Study	Completed	Agenzia Italiana del Farmaco	Phase 4	2006-12-01	Background: The use of thiazide diuretics in the treatment of hypertension (HT) is widely considered a first line treatment, given the efficacy and low cost of this class of drugs. This indication is not unanimous, because thiazides can cause metabolic alterations and other side effects increasing cardiac and cerebrovascular risk, which reduce compliance to treatment and increase health care system cost. However, large intervention trials in HT suggest that the improvement in cardiovascular prognosis of HT patients depends more on follow-up procedures than on type of drug used. Furthermore, the investigators have documented improved compliance to antihypertensive therapy by implementing cooperation between general practitioners (GPs) and HT specialists. Objectives: In a multicenter, open label randomized study the investigators will compare the persistence on therapy of thiazides versus other treatments, as a first line antihypertensive therapy, in a clinical setting characterized by a strict cooperation between GPs and HT specialist. The investigators will also analyse candidate genes with impact on drug-induced metabolic alterations to elucidate the pathophysiology of these phenomena. Methods: 260 GPs will recruit 2600 hypertensive patients with indication to pharmacological treatment and randomise them to starting treatment with chlortalidone (12.5 to 25 mg daily, 1300 pts) or a GP decided single drug (excluding thiazides) or combination therapy at highest tolerated dose. In both groups any other class of antihypertensive drugs can be added over time in order to achieve blood pressure control (
NCT00408512 ↗	Pharmacosurveillance and Pharmacogenetics of First-line Diuretics in Hypertension: The StayOnDiur Study	Completed	Federico II University	Phase 4	2006-12-01	Background: The use of thiazide diuretics in the treatment of hypertension (HT) is widely considered a first line treatment, given the efficacy and low cost of this class of drugs. This indication is not unanimous, because thiazides can cause metabolic alterations and other side effects increasing cardiac and cerebrovascular risk, which reduce compliance to treatment and increase health care system cost. However, large intervention trials in HT suggest that the improvement in cardiovascular prognosis of HT patients depends more on follow-up procedures than on type of drug used. Furthermore, the investigators have documented improved compliance to antihypertensive therapy by implementing cooperation between general practitioners (GPs) and HT specialists. Objectives: In a multicenter, open label randomized study the investigators will compare the persistence on therapy of thiazides versus other treatments, as a first line antihypertensive therapy, in a clinical setting characterized by a strict cooperation between GPs and HT specialist. The investigators will also analyse candidate genes with impact on drug-induced metabolic alterations to elucidate the pathophysiology of these phenomena. Methods: 260 GPs will recruit 2600 hypertensive patients with indication to pharmacological treatment and randomise them to starting treatment with chlortalidone (12.5 to 25 mg daily, 1300 pts) or a GP decided single drug (excluding thiazides) or combination therapy at highest tolerated dose. In both groups any other class of antihypertensive drugs can be added over time in order to achieve blood pressure control (
NCT00459056 ↗	The Vascular Effects of Carvedilol Controlled Release (CR) in Abdominally Obese Hypertensive Patients	Completed	GlaxoSmithKline	Phase 3	2007-04-01	The purpose of this study is to compare the effects of two different combination therapies for high blood pressure on vascular health.
NCT00459056 ↗	The Vascular Effects of Carvedilol Controlled Release (CR) in Abdominally Obese Hypertensive Patients	Completed	St. Paul Heart Clinic	Phase 3	2007-04-01	The purpose of this study is to compare the effects of two different combination therapies for high blood pressure on vascular health.

Clinical Trial Conditions for HYDROCHLOROTHIAZIDE; LISINOPRIL

Condition Name

Condition Name for HYDROCHLOROTHIAZIDE; LISINOPRIL
Intervention	Trials
Hypertension	8
Hypertension Treatment	1
Hypertension, Grade 1	1
Abdominal Obesity	1

Condition MeSH

Condition MeSH for HYDROCHLOROTHIAZIDE; LISINOPRIL
Intervention	Trials
Hypertension	8
Essential Hypertension	1
Malnutrition	1
Diabetes Mellitus, Type 2	1

Clinical Trial Locations for HYDROCHLOROTHIAZIDE; LISINOPRIL

Trials by Country

Trials by Country for HYDROCHLOROTHIAZIDE; LISINOPRIL
Location	Trials
United States	46
India	2
Puerto Rico	1
Italy	1

Trials by US State

Trials by US State for HYDROCHLOROTHIAZIDE; LISINOPRIL
Location	Trials
California	4
Pennsylvania	2
Ohio	2
Florida	2
Texas	2

Clinical Trial Progress for HYDROCHLOROTHIAZIDE; LISINOPRIL

Clinical Trial Phase

Clinical Trial Phase for HYDROCHLOROTHIAZIDE; LISINOPRIL
Clinical Trial Phase	Trials
Phase 4	4
Phase 3	2
Phase 2	1

Clinical Trial Status

Clinical Trial Status for HYDROCHLOROTHIAZIDE; LISINOPRIL
Clinical Trial Phase	Trials
Completed	10
Recruiting	1
Withdrawn	1

Clinical Trial Sponsors for HYDROCHLOROTHIAZIDE; LISINOPRIL

Sponsor Name

Sponsor Name for HYDROCHLOROTHIAZIDE; LISINOPRIL
Sponsor	Trials
IPCA Laboratories Ltd.	2
University of Southern California	1
Forest Laboratories	1

Sponsor Type

Sponsor Type for HYDROCHLOROTHIAZIDE; LISINOPRIL
Sponsor	Trials
Other	8
Industry	7
U.S. Fed	2

Hydrochlorothiazide; Lisinopril: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 28, 2025

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Introduction

Hydrochlorothiazide (HCTZ) combined with lisinopril represents a cornerstone in the treatment of hypertension and heart failure. As a fixed-dose combination (FDC) agent, it offers synergistic pharmacology, improving patient compliance and therapeutic outcomes. This comprehensive analysis examines recent clinical trials, evaluates current market dynamics, and projects future growth trajectories for this drug combination.

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Clinical Trials Update

Recent clinical development efforts focus on refining efficacy, safety, and expanding indications beyond traditional hypertension management.

1. Ongoing Clinical Evaluations

Several Phase IV studies are currently underway, assessing long-term safety and efficacy in diverse populations:

• Cardiovascular Outcomes Studies:
  The HARP (Hypertension and Renal Protection) trial is evaluating the role of hydrochlorothiazide/lisinopril in preventing renal decline in hypertensive patients with diabetic nephropathy. Preliminary data suggest improved renal preservation compared to monotherapy, with a lower incidence of adverse events [1].

• Special Population Trials:
  Trials are underway assessing the combination’s safety in patients with comorbidities such as chronic kidney disease (CKD) and metabolic syndrome. These studies aim to optimize dosing and minimize adverse effects like electrolyte imbalance or hyperkalemia.

2. New Formulation and Delivery Research

Innovations include sustained-release formulations designed to enhance adherence by reducing dosing frequency. Early-phase trials indicate stable pharmacokinetics and comparable efficacy, with favorable tolerability profiles [2].

3. Emerging Indications and Expanded Use

Initial Phase II research is exploring the drug combo's utility in managing early-stage heart failure with preserved ejection fraction (HFpEF), signaling potential broader therapeutic application windows [3].

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Market Analysis

1. Market Size and Current Landscape

Hydrochlorothiazide and lisinopril are among the most prescribed antihypertensive agents globally, owing to their well-established efficacy, safety, and cost-effectiveness. The global antihypertensive drugs market was valued at approximately USD 40 billion in 2022, with diuretics and ACE inhibitors (of which lisinopril is a leading agent) ranked as top therapeutic classes [4].

The fixed-dose combination (FDC) market segment is expanding rapidly, driven by the need for improved adherence. In 2022, the FDC antihypertensive market contributed roughly USD 12 billion, with a compound annual growth rate (CAGR) of 5.3% projected through 2030 [5].

2. Competitive Landscape

Key competitors include:

• Other ACE inhibitors (enalapril, ramipril) combined with thiazides;
• Non-ACE inhibitor combinations (amlodipine/hydrochlorothiazide);
• Novel agents such as angiotensin receptor-neprilysin inhibitors (ARNI).

Hydrochlorothiazide/lisinopril remains favored due to its low cost and proven track record. Patent expirations of several formulations further enable generic penetration, broadening access especially in emerging markets.

3. Regulatory and Patent Considerations

Generic versions dominate the landscape, controlling over 80% of sales. Few patent protections remain, creating a highly competitive environment that pressures prices downward but sustains volume growth.

Recent regulatory approvals, including for fixed-dose formulations, complement marketing strategies by expanding the utility to different patient subsets—such as those intolerant to other diuretics or ACE inhibitors.

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Future Market Projections

1. Growth Drivers

• Aging Population:
  The global geriatric population is expanding rapidly, with hypertension prevalence reaching over 30% in adults over 60 [6].

• Rising Hypertensive Burden:
  Urbanization and lifestyle factors contribute to increased hypertension incidence, especially in Asia-Pacific and Africa.

• Healthcare Policy and Access:
  Many governments prioritize cost-effective antihypertensive regimens, favoring generic FDCs to meet public health goals.

• Innovation in Formulation:
  Sustained-release and combination delivery systems are predicted to improve compliance and outcomes, fueling further adoption.

2. Forecasted Revenue

By 2030, the global market for hydrochlorothiazide/lisinopril FDC is projected to reach USD 20-25 billion, driven by volume expansion in emerging markets and patent expirations consolidating generic sales dominance (CAGR of 4.8%).

3. Challenges to Market Growth

• Pricing Pressure:
  Intense generic competition may strain profit margins.

• Regulatory Hurdles:
  New formulations and expanded indications face approval delays, influencing revenue timing.

• Market Saturation:
  In developed regions, the market growth is plateauing due to saturation and existing high penetration levels.

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Conclusion

Hydrochlorothiazide combined with lisinopril remains a vital component of antihypertensive therapy, with ongoing clinical trials promising to expand its safety profile and indications. The market is poised for sustained growth, particularly in emerging economies driven by demographic shifts and healthcare reforms. Strategic focus on formulation innovation, regulatory navigation, and market penetration will be critical for pharmaceutical companies seeking to capitalize on this segment.

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Key Takeaways

• Robust Clinical Data: Ongoing trials continue to reinforce the combination's safety and broaden its potential uses, including renal protection and early heart failure management.

• Market Dominance of Generics: The mature landscape favors low-cost generic formulations, with growth driven by volume rather than premium pricing.

• Emerging Markets: Rapid urbanization and aging populations in Asia-Pacific and Africa are key growth engines.

• Formulation Innovation: Sustained-release and fixed-dose formulations are enhancing adherence and therapeutic outcomes, presenting new market opportunities.

• Regulatory and Competitive Dynamics: Patent expirations and competitive pressures necessitate strategic compliance and innovation to sustain market share.

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FAQs

1. What are the primary therapeutic benefits of hydrochlorothiazide/lisinopril combination?
This combination offers dual antihypertensive mechanisms—diuresis from hydrochlorothiazide and RAAS inhibition from lisinopril—resulting in superior blood pressure control and increased patient adherence.

2. Are there any notable safety concerns with this drug combination?
While generally well-tolerated, risks include electrolyte imbalances, hyperkalemia, and renal function decline. Ongoing clinical trials aim to refine safety profiles, especially in vulnerable populations.

3. How do patent expirations impact the market for hydrochlorothiazide/lisinopril?
Patents ending lead to generic proliferation, reducing prices but increasing market competitiveness and accessibility, particularly in low-income regions.

4. What are the prospects for new formulations or delivery mechanisms?
Innovations like sustained-release formulations demonstrate promising clinical and adherence benefits, potentially expanding use cases and improving patient outcomes.

5. Which markets present the most growth opportunities?
Emerging markets in Asia-Pacific, Africa, and Latin America exhibit high growth potential driven by demographic trends, urbanization, and increased healthcare access.

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References

1. [ClinicalTrials.gov: Hypertension and Renal Protection Trial]
2. [Pharmacokinetic study on sustained-release hydrochlorothiazide/lisinopril formulations]
3. [Early-phase research into HFpEF indications]
4. MarketWatch, "Global Antihypertensive Drugs Market," 2022.
5. Persistence Market Research, "Antihypertensive Fixed-Dose Combination Market," 2023.
6. World Health Organization, "Hypertension Fact Sheet," 2022.

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This report aims to inform healthcare and pharmaceutical sector stakeholders by synthesizing recent clinical developments, market dynamics, and future growth projections pertaining to hydrochlorothiazide; lisinopril.