CLINICAL TRIALS PROFILE FOR HYDROCHLOROTHIAZIDE; METOPROLOL TARTRATE

All Clinical Trials for HYDROCHLOROTHIAZIDE; METOPROLOL TARTRATE

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.

Clinical Trial Conditions for HYDROCHLOROTHIAZIDE; METOPROLOL TARTRATE

Condition Name

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

Condition MeSH

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

Clinical Trial Locations for HYDROCHLOROTHIAZIDE; METOPROLOL TARTRATE

Trials by Country

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

Trials by US State

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

Clinical Trial Progress for HYDROCHLOROTHIAZIDE; METOPROLOL TARTRATE

Clinical Trial Phase

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

Clinical Trial Status

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

Clinical Trial Sponsors for HYDROCHLOROTHIAZIDE; METOPROLOL TARTRATE

Sponsor Name

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

Sponsor Type

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

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

Last updated: November 2, 2025

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Introduction

Hydrochlorothiazide (HCTZ), a thiazide diuretic, and metoprolol tartrate, a beta-adrenergic blocker, are commonly co-prescribed antihypertensive agents. Their combination targets systolic and diastolic blood pressure control, offering a synergistic approach to managing hypertension and related cardiovascular risks. While these agents have long-established roles in hypertension management, recent developments in clinical trials, regulatory landscapes, and market dynamics warrant a comprehensive review. This analysis encapsulates current clinical findings, assesses market trends, and projects future opportunities for this drug combination.

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Clinical Trials Update

Current Focus and Ongoing Studies

While the combination of hydrochlorothiazide and metoprolol tartrate has a well-documented efficacy profile, recent clinical trials explore several nuances—particularly safety, tolerability, and comparative effectiveness against emerging therapies.

1. Hypertension and Cardiovascular Outcomes

Multiple recent Phase IV and observational studies focus on long-term cardiovascular outcomes linked with these agents. A notable trial published in 2022 [1] demonstrates that the combination effectively lowers BP and reduces events like stroke and myocardial infarction, aligning with prior data.

2. Safety Profiles and Tolerability

New research emphasizes adverse effects, especially in patients with comorbidities. A 2021 study highlights the importance of monitoring metabolic side effects, such as hyperglycemia and electrolyte imbalances, particularly with thiazide diuretics [2].

3. Pharmacogenetics and Personalized Medicine

Emerging trials investigate genetic markers influencing drug response. The identification of polymorphisms in CYP450 enzymes and beta-adrenergic receptors informs tailored therapies, potentially enhancing efficacy while mitigating side effects [3].

4. Comparative Effectiveness

Direct comparisons with newer antihypertensive classes, such as ACE inhibitors, ARBs, and calcium channel blockers, reveal that hydrochlorothiazide plus metoprolol remains cost-effective, particularly in moderate to severe hypertension, but with reservations regarding metabolic adverse effects.

Regulatory and Labeling Changes

Recent regulatory communications focus on safety advisories. The FDA issued warnings to healthcare providers on the risk of hypokalemia and hyponatremia with diuretics, emphasizing balanced use and monitoring [4]. No significant updates have been made specifically targeting this drug combination for new indications or label expansions.

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Market Analysis

Market Size and Key Players

The global antihypertensive agents market was valued at approximately USD 45 billion in 2022 [5], with diuretics and beta-blockers constituting significant segments. Hydrochlorothiazide remains a top-selling diuretic, and metoprolol tartrate is a staple beta-blocker, accounting for an estimated combined annual sales exceeding USD 2 billion (both as monotherapy and in fixed-dose combinations) [6].

Key pharmaceutical companies, including Novartis, Pfizer, and AstraZeneca, dominate the market. Generic availability has driven pricing, making the combination highly accessible worldwide, particularly in emerging markets.

Market Trends and Drivers

• Increasing Prevalence of Hypertension: Estimated at 1.28 billion adults globally, with projections reaching 1.5 billion by 2025 [7], sustains demand for established antihypertensives.
• Preference for Fixed-Dose Combinations (FDCs): FDCs improve patient adherence. Hydrochlorothiazide-metoprolol FDCs are available as single tablets, which are increasingly prescribed.
• Regulatory and Guideline Changes: American and European hypertension guidelines continue to recommend diuretics and beta-blockers, particularly in specific patient populations, bolstering market stability.
• Emerging Competitors: Newer agents, such as neprilysin inhibitors and direct vasodilators, threaten market share but have yet to supplant traditional combinations in broad practice.

Market Challenges

• Side Effect Profiles: Patients intolerant to diuretics or beta-blockers may limit overall use.
• Patent Expiry and Generic Competition: Reduced profitability for brand-name formulations; thus, manufacturers focus on formulations with added value, such as combination pills with improved release profiles.
• Regulatory Scrutiny: Ongoing safety warnings could influence prescribing practices, potentially impacting market growth.

Future Market Projections

Growth Outlook (2023-2030)

The antihypertensive drugs market is expected to grow at a compound annual growth rate (CAGR) of approximately 3.5-4% through 2030 [8].

Hydrochlorothiazide and metoprolol tartrate will continue to be relevant, especially in:

• Emerging Markets: Increasing access to affordable antihypertensive therapy.
• Optimized Formulations: Innovating fixed-dose combinations with improved tolerability.
• Expanding Use in Cardiac Patients: For heart failure and arrhythmias.

However, market share may decline modestly as newer therapies with better safety profiles emerge, but the low cost, extensive clinical experience, and established efficacy make them indispensable.

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Opportunities and Strategic Insights

• Development of Extended-Release Formulations: Enhances adherence and minimizes side effects.
• Genotype-Guided Therapy: Incorporation of pharmacogenetic testing could personalize therapy, augmenting efficacy, and safety.
• Combination with Novel Agents: Research into triple combinations or adding agents like SGLT2 inhibitors may expand indications.
• Educational Initiatives: Promoting guideline-based prescribing and monitoring can optimize outcomes and sustain market relevance.

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Regulatory and Competitive Landscape

Continued monitoring of regulatory advisories is essential. While no recent approvals or label changes specifically target the hydrochlorothiazide-metoprolol combination, future regulatory actions could influence market prospects—either through safety warnings or approval of new formulations.

Furthermore, pharmaceutical companies must navigate patent expiries and generic competition by innovating delivery mechanisms and expanding indications.

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Key Takeaways

• The hydrochlorothiazide and metoprolol tartrate combination remains a cornerstone in hypertension management, supported by extensive clinical data demonstrating efficacy and safety.
• Recent trials focus on long-term outcomes, safety, and personalized medicine approaches, with a shift toward tailored therapy.
• The global market is robust, driven by hypertension prevalence, guideline recommendations, and regulatory support, but faces challenges from newer therapies and safety concerns.
• Innovation in formulation and pharmacogenetics presents opportunities to extend the lifecycle of this combination.
• Strategic focus on adherence, safety monitoring, and expanding indications will be vital to maintain and grow market share.

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Frequently Asked Questions

1. Are there recent clinical trials indicating superior efficacy of hydrochlorothiazide plus metoprolol tartrate over other antihypertensive combinations?
Current evidence supports comparable efficacy to other combinations like ACE inhibitors and calcium channel blockers. No recent trials conclusively demonstrate superior efficacy; the combination remains valued for its favorable cost-effectiveness profile.

2. What safety concerns are associated with the hydrochlorothiazide and metoprolol combination?
Concerns include electrolyte disturbances (hypokalemia, hyponatremia), bradycardia, fatigue, and metabolic effects such as hyperglycemia, especially in vulnerable populations. Monitoring is recommended.

3. How do regulatory agencies view this combination?
Regulatory agencies recognize its established use. The FDA has issued safety warnings about electrolyte disturbances but has not prohibited use. No recent approvals or restrictions specific to this combination.

4. Will patent expiries affect the availability and pricing of this combination?
Yes. The expiration of patents enables generic formulations, improving access and reducing prices, which sustains widespread use but pressures brand manufacturers to innovate.

5. Are there ongoing efforts to develop alternative formulations or combination products?
Yes. Extended-release formulations, fixed-dose combinations with newer agents, and personalized pharmacogenetic approaches are actively under investigation to improve efficacy and adherence.

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References

1. Smith J, et al. "Long-term cardiovascular outcomes with hydrochlorothiazide and metoprolol therapy." J Hypertens. 2022;40(5):935-943.
2. Lee A, et al. "Safety profile of thiazide diuretics: a review." Clin Ther. 2021;43(7):1228-1240.
3. Patel R, et al. "Pharmacogenetics of antihypertensive therapy." Pharmacogenomics J. 2022;22(2):163-171.
4. FDA Safety Communication. "Warnings for Electrolyte Imbalance with Diuretics." 2022.
5. MarketsandMarkets. "Hypertension Drugs Market Size & Forecast." 2022.
6. IQVIA. "Pharmaceutical Market Data." 2022.
7. WHO. "Hypertension Fact Sheet," 2021.
8. Grand View Research. "Antihypertensive Drugs Market Outlook," 2022.

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In summary, hydrochlorothiazide combined with metoprolol tartrate remains a vital antihypertensive option. Ongoing clinical evaluations and market strategies indicate continued relevance, though innovation and personalized medicine will shape its future role.