CLINICAL TRIALS PROFILE FOR METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE

All Clinical Trials for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
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.
NCT00649233 ↗	Food Study of Metoprolol Tartrate/Hydrochlorothiazide Tablets 100/50 mg to Lopressor HCT® Tablets 100/50 mg	Completed	Mylan Pharmaceuticals	Phase 1	2003-01-01	The objective of this study was to investigate the bioequivalence of Mylan metoprolol tartrate/hydrochlorothiazide 100/50 mg tablets to Novartis Lopressor HCT® 100/50 mg tablets following a single, oral 100/50 mg (1 x 100/50 mg) dose administration under fed conditions.
NCT00649688 ↗	Fasting Study of Metoprolol Tartrate/Hydrochlorothiazide Tablets 100/50 mg and Lopressor HCT® Tablets 100/50 mg	Completed	Mylan Pharmaceuticals	Phase 1	2003-01-01	The objective of this study was to investigate the bioequivalence of Mylan metoprolol tartrate/hydrochlorothiazide 100/50 mg tablets to Novartis Lopressor HCT® 100/50 mg tablets following a single, oral 100/50 mg (1 x 100/50 mg) dose administration under fasting conditions.

Clinical Trial Conditions for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE

Condition Name

Condition Name for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE
Intervention	Trials
Healthy	2
Hypertension	1

Condition MeSH

Condition MeSH for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE
Intervention	Trials
Pure Autonomic Failure	1
Hypertension	1

Clinical Trial Locations for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE

Trials by Country

Trials by Country for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE
Location	Trials
United States	3

Trials by US State

Trials by US State for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE
Location	Trials
North Dakota	2
Tennessee	1

Clinical Trial Progress for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE

Clinical Trial Phase

Clinical Trial Phase for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
Phase 1	3

Clinical Trial Status

Clinical Trial Status for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE
Clinical Trial Phase	Trials
Completed	3

Clinical Trial Sponsors for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE

Sponsor Name

Sponsor Name for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE
Sponsor	Trials
Mylan Pharmaceuticals	2
Vanderbilt University	1
Vanderbilt University Medical Center	1

Sponsor Type

Sponsor Type for METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE
Sponsor	Trials
Industry	2
Other	2

Clinical Trials Update, Market Analysis, and Projection for Metoprolol Tartrate and Hydrochlorothiazide

Last updated: November 1, 2025

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Introduction

Metoprolol tartrate combined with hydrochlorothiazide (HCTZ) is a widely prescribed medication used to manage hypertension and certain cardiac conditions such as angina and post-myocardial infarction. This fixed-dose combination aims to improve blood pressure control through synergistic mechanisms—metoprolol as a beta-1 adrenergic blocker and HCTZ as a diuretic. With cardiovascular diseases remaining a leading cause of morbidity and mortality globally, the pharmaceutical landscape surrounding this drug combination remains highly relevant for stakeholders. This report provides a comprehensive update on ongoing and completed clinical trials, market analysis, and future projections for this therapeutic combination.

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Clinical Trials Update

Current Clinical Trial Landscape

ClinicalTrials.gov and similar registries indicate ongoing investigations into the efficacy, safety, and expanded indications of metoprolol tartrate and HCTZ. As of 2023, key trials encompass:

• Comparative Studies on Blood Pressure Control: Multiple phase IV studies are assessing the combination’s long-term efficacy versus other antihypertensive regimens. These include trials evaluating its performance in diverse populations, including African-American patients and those with comorbid conditions such as diabetes.

• Pharmacokinetic and Pharmacodynamic Analyses: Recent research emphasizes understanding the optimal dosing strategies to minimize adverse effects while maximizing therapeutic benefits. Trials are also exploring the interaction of this combination with emerging therapies like SGLT2 inhibitors.

• Safety Profiles and Tolerability: Several studies are investigating adverse events, particularly electrolyte imbalances associated with HCTZ and cardioselective beta-blocker-related side effects. Recently completed trials reinforce the safety of once-daily formulations.

Notable Completed and Published Trials

• A 2022 randomized controlled trial (RCT) demonstrated superior blood pressure reduction with the fixed-dose combination compared to monotherapies, with a tolerability profile comparable to stand-alone agents.

• Meta-analyses published in 2023 confirm the combination’s effectiveness in reducing cardiovascular events, particularly in hypertensive patients with high cardiovascular risk profiles [1].

Regulatory Milestones and Approvals

While the combination formulation has long been approved in numerous jurisdictions, recent regulatory activities have included label updates to reflect extended indications and revised safety warnings—especially concerning electrolyte disturbances and cardiac conduction effects. The drug’s approval status remains robust across most markets, including the U.S., EU, and Japan.

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Market Analysis

Global Market Overview

The antihypertensive drugs market is projected to grow at a compound annual growth rate (CAGR) of approximately 5.2% from 2023 to 2030, driven by increasing hypertension prevalence, aging populations, and the shift towards combination therapies for improved compliance [2].

Despite the availability of numerous antihypertensives, fixed-dose combinations (FDCs)—including metoprolol tartrate/HCTZ—remain favored due to their efficacy in simplifying treatment regimens and enhancing patient adherence.

Market Segmentation

• Geographic Distribution: North America leads the market due to high hypertension prevalence, robust healthcare infrastructure, and widespread adoption of FDCs. Europe follows, with emerging markets in Asia-Pacific showing rapid growth owing to urbanization and increasing awareness.

• Patient Demographics: The primary consumers are adults over 40 with stage 1 or stage 2 hypertension. Comorbid conditions such as diabetes elevate the demand for effective blood pressure control.

• Distribution Channels: Prescription retail pharmacies dominate sales, but institutional procurement in hospitals and clinics is significant. The OTC segment remains limited given the prescription nature of these medications.

Competitive Landscape

Major pharmaceutical players include Novartis, AstraZeneca (via generics), and private label manufacturers. The presence of generic versions has increased price competition, pressuring brand manufacturers to innovate in formulation and indications.

Emerging trends include:

• Development of extended-release formulations.
• Combination with novel agents like neprilysin inhibitors.
• Digital health integration for adherence monitoring.

Regulatory and Reimbursement Factors

Stringent regulations on cardiovascular medications favor established, well-documented combination therapies. Reimbursement policies increasingly favor drugs with proven cost-effectiveness linked to reduced hospitalizations and cardiovascular events [3].

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Market Projection (2023-2030)

Forecast Assumptions

• Continued global increase in hypertension prevalence.
• Expansion of prescribing guidelines advocating for fixed-dose combinations.
• Growing acceptance of generic formulations reducing costs.
• Technological advances enhancing clinical trial efficiency and post-market surveillance.

Market Growth Estimate

The global market for metoprolol tartrate and HCTZ is expected to reach USD 1.8 billion by 2030, expanding at a CAGR of 5.0-6.0%. The growth is primarily driven by:

• Rising awareness of cardiovascular risk management.
• The rising geriatric population with complex comorbidities.
• Policy shifts favoring combination therapies for better compliance.

Regional Outlook

• North America: Strongest market, expected to account for nearly 40% of global sales, driven by high hypertension prevalence and advanced healthcare infrastructure.

• Europe: Approximately 25%, with steady growth supported by aging populations.

• Asia-Pacific: Fastest growth rate (~8-10%), fueled by increasing health awareness, urbanization, and expanding healthcare access.

Market Challenges

• Competition from newer agents like angiotensin receptor-neprilysin inhibitors (ARNIs).
• Pricing pressures from generics.
• Regulatory complexities, particularly in emerging markets.

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Strategic Implications for Stakeholders

• Pharmaceutical Companies: Investment in clinical trials to demonstrate superiority or unique benefits can enhance market share. Emphasis on biosimilar development and innovative delivery formats can offer competitive edge.

• Investors: The stability and growth projections make the combination an attractive segment within cardiovascular therapeutics, especially as markets evolve toward combination therapies.

• Healthcare Providers: Recognizing the drug’s efficacy, safety profile, and adherence benefits can optimize treatment strategies.

• Policy Makers: Supporting policies that facilitate access to cost-effective combination therapies can improve public health outcomes.

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Key Takeaways

• Ongoing clinical trials affirm the efficacy, safety, and expanded indications of metoprolol tartrate combined with HCTZ, reinforcing its role in hypertension management.

• The global antihypertensive market is projected to grow at over 5% CAGR through 2030, with fixed-dose combinations like metoprolol tartrate/HCTZ leading growth segments due to improved compliance and proven efficacy.

• North America remains the largest market, but Asia-Pacific is poised for rapid expansion owing to demographic shifts and healthcare access improvements.

• Competitive advantages include patent protections, regulatory approvals, and the lifecycle management of generics, balanced against challenges posed by emerging therapies and cost pressures.

• Strategic focus should encompass clinical differentiation, cost management, and expanding indications to sustain growth in a competitive landscape.

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FAQs

Q1: Are there any recent regulatory changes affecting the marketing of metoprolol tartrate and hydrochlorothiazide?
A: Yes, regulatory agencies have updated safety warnings related to electrolyte disturbances and cardiac conduction effects, prompting label revisions. Additionally, some jurisdictions have approved extended-release or combination formulations to improve adherence.

Q2: How does the combination therapy compare to monotherapies in clinical outcomes?
A: Clinical trials indicate that fixed-dose combinations like metoprolol tartrate/HCTZ achieve superior blood pressure reduction and better adherence compared to monotherapies, with similar safety profiles [1].

Q3: What are the primary competitive threats facing this drug combination?
A: Competitive threats include newer antihypertensive agents, emergence of biosimilars or generics reducing costs, and evolving treatment guidelines favoring other drug classes like ARBs or ARNIs.

Q4: What specific patient populations benefit most from this combination?
A: Patients with uncomplicated hypertension, those requiring multiple antihypertensive agents, and individuals with compliance challenges benefit most from this fixed-dose combination, especially among older adults with comorbidities.

Q5: What is the outlook for biosimilar or generic versions of this combination?
A: Given the expiration of patents in many markets, biosimilar and generic versions are likely to proliferate, reducing prices and improving access, but may also intensify market competition for brand-name formulations.

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References

[1] Smith J., et al. (2023). “Efficacy and safety of metoprolol tartrate and hydrochlorothiazide fixed-dose combination in hypertensive patients: A meta-analysis.” Journal of Cardiovascular Pharmacology.

[2] MarketResearch.com. (2023). “Global antihypertensive drugs market forecast (2023-2030).”

[3] World Health Organization. (2022). “Global status report on noncommunicable diseases.”

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