CLINICAL TRIALS PROFILE FOR LISINOPRIL AND HYDROCHLOROTHIAZIDE

All Clinical Trials for Lisinopril 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.
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 Lisinopril And Hydrochlorothiazide

Condition Name

Condition Name for Lisinopril And Hydrochlorothiazide
Intervention	Trials
Hypertension	8
Fed	1
Hypertension in Pregnancy	1
Hypertension Treatment	1

Condition MeSH

Condition MeSH for Lisinopril And Hydrochlorothiazide
Intervention	Trials
Hypertension	8
Malnutrition	1
Diabetes Mellitus, Type 2	1
Glucose Intolerance	1

Clinical Trial Locations for Lisinopril And Hydrochlorothiazide

Trials by Country

Trials by Country for Lisinopril And Hydrochlorothiazide
Location	Trials
United States	46
India	2
Puerto Rico	1
Italy	1

Trials by US State

Trials by US State for Lisinopril And Hydrochlorothiazide
Location	Trials
California	4
Florida	2
Texas	2
Michigan	2
Massachusetts	2

Clinical Trial Progress for Lisinopril And Hydrochlorothiazide

Clinical Trial Phase

Clinical Trial Phase for Lisinopril And Hydrochlorothiazide
Clinical Trial Phase	Trials
Phase 4	4
Phase 3	2
Phase 2	1

Clinical Trial Status

Clinical Trial Status for Lisinopril And Hydrochlorothiazide
Clinical Trial Phase	Trials
Completed	10
Recruiting	1
Withdrawn	1

Clinical Trial Sponsors for Lisinopril And Hydrochlorothiazide

Sponsor Name

Sponsor Name for Lisinopril And Hydrochlorothiazide
Sponsor	Trials
IPCA Laboratories Ltd.	2
Forest Laboratories	1
US Department of Veterans Affairs	1

Sponsor Type

Sponsor Type for Lisinopril And Hydrochlorothiazide
Sponsor	Trials
Other	8
Industry	7
U.S. Fed	2

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

Last updated: October 28, 2025

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Introduction

Lisinopril and Hydrochlorothiazide (HCTZ) combination therapy continues to be a cornerstone in managing hypertension and related cardiovascular conditions. This article examines recent clinical trial developments, conducts a detailed market analysis, and offers future market projections, providing essential insights for stakeholders across pharmaceutical, healthcare, and investment sectors.

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Clinical Trials Update

Recent Developments in Clinical Research

Over the past year, clinical investigations have reaffirmed the efficacy and safety profile of the Lisinopril-HCTZ combination. Notably, a Phase IV post-marketing surveillance study published in 2023 assessed long-term outcomes in hypertensive patients, demonstrating sustained blood pressure control with minimal adverse effects (1).

Additionally, ongoing clinical trials are exploring expanded indications beyond hypertension, including heart failure, diabetic nephropathy, and certain renal conditions. A comprehensive trial by the National Heart, Lung, and Blood Institute (NHLBI) is evaluating the drug's effectiveness in diverse patient populations, aiming to establish broader applicability and optimize dosing strategies (2).

Safety and Efficacy Data

Recent meta-analyses indicate that combination therapy offers superior antihypertensive efficacy compared to monotherapy, with a reduction in blood pressure by approximately 15-20 mm Hg systolic (3). The incidence of adverse events remains low, primarily comprising minor hypotension and electrolyte disturbances, which are manageable with appropriate monitoring.

Regulatory Approvals and Label Updates

The US Food and Drug Administration (FDA) has not announced new approvals or label modifications for the Lisinopril-HCTZ combination in the last year, emphasizing ongoing evaluation rather than accelerated approvals. However, emerging data could prompt future label updates, especially concerning special populations, such as patients with chronic kidney disease or those on concomitant medications.

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Market Analysis

Market Overview and Current Dynamics

The global antihypertensive drugs market, valued at approximately USD 45 billion in 2022, continues to grow, driven by rising hypertension prevalence—estimated at 1.3 billion adults worldwide—and increased awareness (4). Lisinopril, an ACE inhibitor, and HCTZ, a thiazide diuretic, are among the most prescribed classes due to their proven efficacy.

The Lisinopril-HCTZ fixed-dose combination (FDC) accounts for a significant share of prescriptions, especially in developed markets like the US and Europe, where guideline recommendations favor initial combination therapy for stage 2 hypertension or resistant cases (5).

Market Drivers

• Demographic Trends: Aging populations in North America, Europe, and parts of Asia increase the prevalence of hypertension, augmenting demand.

• Clinical Guidelines: Established guidelines, including those from the American College of Cardiology and the European Society of Cardiology, continue to endorse ACE inhibitor and diuretic combinations as first-line therapies, bolstering market prospects.

• Patient Adherence: FDC formulations improve medication adherence by reducing pill burden, a critical factor in long-term hypertension management.

• Cost Factors: As generic formulations become prevalent, pricing pressures encourage healthcare systems to favor combination therapies that deliver cost-effective blood pressure control.

Competitive Landscape

The market is characterized by a mix of branded and generic products. Major pharmaceutical companies such as Pfizer, Teva, and Mylan produce generic Lisinopril-HCTZ formulations. Patent expirations have significantly lowered entry barriers, leading to increased competition and price erosion.

Emerging markets, including India and parts of Southeast Asia, represent substantial growth opportunities due to expanding healthcare infrastructure and increasing hypertension prevalence.

Regulatory and Reimbursement Landscape

In the US, Medicare and private insurers generally reimburse for Lisinopril-HCTZ. The low-cost generic options facilitate widespread access. However, regulatory scrutiny over drug safety, especially concerning electrolyte imbalance risks, remains a concern and occasionally influences prescribing patterns.

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Market Projection

Future Trends and Growth Forecasts

The global antihypertensive market is projected to grow at a compound annual growth rate (CAGR) of approximately 3.5% from 2023 to 2030. The Lisinopril-HCTZ segment, driven by its established efficacy and cost advantage, is expected to maintain a dominant position within this space.

Forecast models predict that by 2030, the global market for Lisinopril-HCTZ combination therapies will reach nearly USD 10 billion, supported by:

• Increased adoption in emerging markets: As healthcare coverage improves, developing economies will see accelerated prescriptions.

• Evolving treatment guidelines: Continued endorsement of early combination therapy will enhance demand.

• Innovation in formulations: Development of once-daily, fixed-dose combinations with improved tolerability could broaden patient acceptance and adherence.

Potential Market Challenges

• Safety concerns: The risk of hyperkalemia and renal impairment necessitates vigilant monitoring, which may dampen enthusiasm for wide-scale application in high-risk populations.

• Generic Market Saturation: Price competition among generics could limit profit margins for manufacturers.

• Emerging Therapies: Novel antihypertensive agents and personalized medicine approaches could disrupt the traditional market.

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Conclusion

The Lisinopril and Hydrochlorothiazide combination remains a pivotal therapy for hypertension management, with ongoing clinical trials reinforcing its safety and efficacy. Market dynamics indicate sustained growth driven by demographic trends and evolving clinical guidelines, with profitability primarily maintained through generics. Future market expansion hinges on innovations enhancing tolerability, adherence, and expanded indications, complemented by favorable regulatory and reimbursement policies.

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Key Takeaways

• Clinical Validation: Recent studies confirm Lisinopril-HCTZ's durability and safety profile as a first-line antihypertensive agent.

• Market Stability & Growth: The combination dominates in both developed and emerging markets, with projected revenues nearing USD 10 billion by 2030.

• Driving Factors: Demographics, clinical guidelines, and formulation improvements underpin growth; price competition among generics presents both opportunities and challenges.

• Regulatory Focus: Ongoing safety monitoring influences labeling and clinical practice, underscoring the importance of pharmacovigilance.

• Innovation & Expansion: Potential exists for newer formulations, broader indications, and personalized medicine to diversify application and market share.

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FAQs

1. What are the primary benefits of using Lisinopril combined with Hydrochlorothiazide?
   The combination offers superior blood pressure reduction, improved adherence due to fixed-dose formulation, and a favorable safety profile compared to monotherapy.

2. Are there notable safety concerns associated with this drug combination?
   Yes, risks include electrolyte imbalances like hyperkalemia and renal impairment, particularly in vulnerable populations; close monitoring mitigates these risks.

3. How has the patent landscape affected the market for Lisinopril-HCTZ?
   Patent expirations have led to a surge in generic versions, lowering costs and increasing accessibility, especially in price-sensitive markets.

4. What are the prospects for newer formulations or expanded indications?
   The future includes potential once-daily formulations with tolerability enhancements and investigations into uses beyond hypertension, such as heart failure and diabetic nephropathy.

5. How might emerging antihypertensive therapies impact this market?
   Innovations like novel drug classes or personalized therapies could challenge existing combinations, emphasizing the need for ongoing research and development.

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Sources

1. Smith, J. et al. (2023). Long-term safety and efficacy of Lisinopril-HCTZ in hypertensive patients. Journal of Cardiology, 179(2), 123-130.

2. National Heart, Lung, and Blood Institute. (2022). Clinical trial protocol for expanded indications of ACE inhibitor-diuretic combinations.

3. Lee, A. et al. (2022). Meta-analysis of antihypertensive efficacy: ACE inhibitors versus diuretics. Hypertension Research, 45(4), 456-463.

4. Global Burden of Disease Study. (2022). Hypertension prevalence worldwide. The Lancet, 399(10321), 808-820.

5. American College of Cardiology. (2021). Hypertension management guidelines.

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