CLINICAL TRIALS PROFILE FOR HYDROCHLOROTHIAZIDE; METOPROLOL TARTRATE

All Clinical Trials for HYDROCHLOROTHIAZIDE; METOPROLOL TARTRATE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
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.
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.

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
Hypertension	1
Pure Autonomic Failure	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 and Metoprolol Tartrate: Clinical Trials, Market Analysis, and Projections

Introduction

Hydrochlorothiazide and metoprolol tartrate are commonly used in combination to treat hypertension (high blood pressure) and other cardiovascular conditions. This article delves into the current clinical trials, market analysis, and future projections for this drug combination.

Clinical Trials

Several clinical trials have been conducted to evaluate the bioequivalence and efficacy of hydrochlorothiazide and metoprolol tartrate combinations.

Bioequivalence Studies

Two notable clinical trials were conducted by Mylan Pharmaceuticals, Inc. to compare the bioequivalence of Mylan's metoprolol tartrate/hydrochlorothiazide tablets with Novartis's Lopressor HCT® tablets.

• NCT00649233: This Phase 1 trial investigated the bioequivalence under fed conditions. The study aimed to determine if Mylan's 100/50 mg tablets were bioequivalent to Novartis's 100/50 mg tablets after a single oral dose in healthy volunteers[1].
• NCT00649688: This trial was similar but conducted under fasting conditions to assess bioequivalence in a different metabolic state[1].

These studies are crucial for ensuring that generic versions of the drug are as effective and safe as the brand-name versions.

Market Analysis

Market Size and Growth

The global metoprolol tartrate market, which includes combinations with hydrochlorothiazide, is projected to grow significantly.

• By 2027, the metoprolol tartrate market is estimated to reach $868.3 million, growing at a CAGR of 5.2% during the forecast period 2022-2027[2].
• Another report estimates the global metoprolol tartrate market to be valued at $6,101.4 million in 2022, with a CAGR of 3.3% from 2022 to 2030[3].

Market Drivers

Several factors are driving the growth of the metoprolol tartrate market:

• Increasing Prevalence of Hypertension: The rising number of adults with hypertension, particularly in low- and middle-income countries, is a significant driver. According to the World Health Organization (WHO), approximately 1.28 billion adults aged 30-79 years globally have hypertension[2][3].
• Growing Geriatric Population: The increasing elderly population, who are more prone to cardiovascular diseases, is another key factor[5].
• Sedentary Lifestyle: The rise in sedentary lifestyles among the general population contributes to the higher incidence of cardiovascular diseases, thereby increasing the demand for metoprolol tartrate[2][5].

Market Segmentation

The metoprolol tartrate market is segmented based on application, with the hypertension segment holding the largest market share.

• Hypertension: This segment dominates due to the widespread use of metoprolol tartrate for treating high blood pressure[2][3].
• Cardiovascular Diseases: The drug is also used to treat angina and improve survival after a heart attack, contributing to its market growth[2][3].

Geographical Analysis

Geographically, the market is led by North America, with the Asia-Pacific region expected to grow at the fastest CAGR.

• North America: This region accounted for the highest revenue share in 2021 due to the high prevalence of heart diseases[2].
• Asia-Pacific: The region is expected to grow rapidly due to the increasing application of metoprolol tartrate for treating hypertension and angina[2].

Projections and Future Outlook

Market Growth Projections

The metoprolol tartrate market is expected to continue growing due to several factors:

• Increasing Product Launches: New product launches by market players are anticipated to drive market growth[3].
• COVID-19 Impact: Research on using metoprolol tartrate for treating COVID-19-associated complications, such as Acute Respiratory Distress Syndrome (ARDS), may further boost the market[3].

Challenges and Restraints

Despite the positive outlook, there are challenges that could impede market growth:

• Side Effects: The rising side effects associated with metoprolol tartrate, such as bradycardia and worsening congestive heart failure, are significant concerns[4][5].
• Government Regulations: Stringent government regulations on metoprolol tartrate also pose a challenge to market growth[2][5].

Key Applications and Dosage

Dosage Forms and Strengths

Hydrochlorothiazide and metoprolol tartrate are available in various dosage forms and strengths:

• Tablets: Available in combinations such as 50/25 mg, 100/25 mg, and 100/50 mg[4].

Clinical Use

The combination is used to treat:

• Hypertension: To reduce high blood pressure and prevent heart strokes, heart attacks, and kidney problems[3][5].
• Angina: To treat chest pain and improve survival after a heart attack[3][5].

Safety and Precautions

Contraindications

The combination is contraindicated in patients with:

• Hypersensitivity: To metoprolol tartrate or hydrochlorothiazide or other sulfonamide-derived drugs[4].
• Cardiogenic Shock: Or decompensated heart failure[4].
• Sinus Bradycardia: Sick sinus syndrome, and greater than first-degree block unless a permanent pacemaker is in place[4].

Warnings and Precautions

• Abrupt Cessation: May exacerbate myocardial ischemia[4].
• Bradycardia: Including sinus pause, heart block, and cardiac arrest have occurred with the use of this combination[4].

"Metoprolol tartrate is a beta-adrenergic receptor blocking agent. The effective dosage range of Metoprolol Tartrate Tablets USP is 100 mg to 400 mg per day"[2].

Key Takeaways

• The metoprolol tartrate market, including combinations with hydrochlorothiazide, is projected to grow significantly due to increasing hypertension prevalence and a growing geriatric population.
• Clinical trials have established the bioequivalence of generic versions of the drug.
• The market is driven by factors such as new product launches and the COVID-19 pandemic, but faces challenges like side effects and government regulations.
• The combination is widely used for treating hypertension and angina, with specific dosage forms and strengths available.

FAQs

What are the primary uses of hydrochlorothiazide and metoprolol tartrate?

Hydrochlorothiazide and metoprolol tartrate are primarily used to treat hypertension (high blood pressure) and angina (chest pain), and to improve survival after a heart attack.

What are the common dosage forms and strengths of hydrochlorothiazide and metoprolol tartrate?

The combination is available in tablet forms with strengths such as 50/25 mg, 100/25 mg, and 100/50 mg.

What are the major drivers of the metoprolol tartrate market?

The major drivers include the increasing prevalence of hypertension, the growing geriatric population, and the rise in sedentary lifestyles.

What are the potential side effects of hydrochlorothiazide and metoprolol tartrate?

Potential side effects include bradycardia, worsening congestive heart failure, and increased post-implantation loss and decreased neonatal survival in animal studies.

Are there any contraindications for using hydrochlorothiazide and metoprolol tartrate?

Yes, the combination is contraindicated in patients with hypersensitivity to the drugs, cardiogenic shock, decompensated heart failure, sinus bradycardia, and greater than first-degree block unless a permanent pacemaker is in place.

Sources

1. Synapse by Patsnap - Hydrochlorothiazide/Metoprolol Tartrate - Drug Targets, Indications, Clinical Trials[1].
2. IndustryARC - Metoprolol Tartrate Market Size Report, 2022-2027[2].
3. Coherent Market Insights - Metoprolol Tartrate Market Size, Trends and Forecast to 2030[3].
4. FDA - Lopressor HCT Label[4].
5. Allied Market Research - Metoprolol Tartrate Market[5].