CLINICAL TRIALS PROFILE FOR HYDROCHLOROTHIAZIDE; LOSARTAN POTASSIUM

All Clinical Trials for Hydrochlorothiazide; Losartan Potassium

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00157963 ↗	Hydrochlorothiazide (+) Losartan Potassium vs. Amlodipine Comparative Study (0954A-314)	Completed	Merck Sharp & Dohme Corp.	Phase 4	2005-02-05	An efficacy and safety study of hydrochlorothiazide (+) losartan potassium compared to amlodipine at week 12 in Korean patients with essential hypertension
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.
NCT00289887 ↗	Obese Hypertension Study (0954-315)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2006-02-01	This is a 16-week study to evaluate high systolic and diastolic blood pressure following treatment in obese, hypertensive, adult patients.
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 (<140/90 mmHg). Follow-up will last 2 years. Blood sample and urine analyses, carotid and cardiac ultrasound will be performed at baseline and scheduled time points. Genotyping will be performed by sequencing. Data will be collected and stored using a web based centralized Case Report Form (CRF) Expected results: Results will highlight whether a follow-up strategy based on tight cooperation between GPs and HT specialists can allow the use of thiazides as first line antihypertensive therapy without any negative effect on persistence, adherence and efficacy of the treatment. These data can be used to reduce total burden of the Health Care System in HT by replacing more expensive drugs with diuretics in the 50% of hypertensive patients, who do not receive this class of drugs. Furthermore, the pharmacogenetic approach may clarify the pathophysiological mechanisms of drug-induced metabolic side effects
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 (<140/90 mmHg). Follow-up will last 2 years. Blood sample and urine analyses, carotid and cardiac ultrasound will be performed at baseline and scheduled time points. Genotyping will be performed by sequencing. Data will be collected and stored using a web based centralized Case Report Form (CRF) Expected results: Results will highlight whether a follow-up strategy based on tight cooperation between GPs and HT specialists can allow the use of thiazides as first line antihypertensive therapy without any negative effect on persistence, adherence and efficacy of the treatment. These data can be used to reduce total burden of the Health Care System in HT by replacing more expensive drugs with diuretics in the 50% of hypertensive patients, who do not receive this class of drugs. Furthermore, the pharmacogenetic approach may clarify the pathophysiological mechanisms of drug-induced metabolic side effects
NCT00449111 ↗	An Open Label Study to Assess the Efficacy, Safety and Tolerability of COZAAR Plus (Losartan Potassium 50mg/Hydrochlorothiazide 12.5mg) Possibly Titrated up to COZAAR Plus-F (Losartan Potassium 100mg/Hydrochlorothiazide 25mg) in Patients With Essent	Terminated	Merck Sharp & Dohme Corp.	Phase 3	2006-03-13	Evaluate blood pressure after 6 weeks of treatment with COZAAR plus.

Clinical Trial Conditions for Hydrochlorothiazide; Losartan Potassium

Condition Name

Condition Name for Hydrochlorothiazide; Losartan Potassium
Intervention	Trials
Hypertension	9
Healthy	4
Essential Hypertension	2

Condition MeSH

Condition MeSH for Hydrochlorothiazide; Losartan Potassium
Intervention	Trials
Hypertension	10
Essential Hypertension	5
Malnutrition	2
Pure Autonomic Failure	1

Clinical Trial Locations for Hydrochlorothiazide; Losartan Potassium

Trials by Country

Trials by Country for Hydrochlorothiazide; Losartan Potassium
Location	Trials
United States	5
Japan	1
Italy	1
China	1
India	1

Trials by US State

Trials by US State for Hydrochlorothiazide; Losartan Potassium
Location	Trials
North Dakota	2
Texas	2
Tennessee	1

Clinical Trial Progress for Hydrochlorothiazide; Losartan Potassium

Clinical Trial Phase

Clinical Trial Phase for Hydrochlorothiazide; Losartan Potassium
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	5
Phase 1	5

Clinical Trial Status

Clinical Trial Status for Hydrochlorothiazide; Losartan Potassium
Clinical Trial Phase	Trials
Completed	13
Recruiting	1
Terminated	1

Clinical Trial Sponsors for Hydrochlorothiazide; Losartan Potassium

Sponsor Name

Sponsor Name for Hydrochlorothiazide; Losartan Potassium
Sponsor	Trials
Merck Sharp & Dohme Corp.	5
Roxane Laboratories	2
Teva Pharmaceuticals USA	2

Sponsor Type

Sponsor Type for Hydrochlorothiazide; Losartan Potassium
Sponsor	Trials
Industry	11
Other	6

Hydrochlorothiazide and Losartan Potassium: Clinical Trials, Market Analysis, and Projections

Introduction

Hydrochlorothiazide (HCTZ) and Losartan Potassium are two widely used medications in the management of hypertension and related conditions. This article provides an update on recent clinical trials, market analysis, and projections for these drugs.

Hydrochlorothiazide: Mechanism and Uses

Hydrochlorothiazide is a thiazide diuretic that works by inhibiting the sodium-chloride cotransporter in the distal convoluted tubule of the kidney, leading to increased excretion of water and electrolytes. This mechanism helps in reducing edema and lowering blood pressure. HCTZ is primarily used to treat hypertension, edema, and kidney calculi, and it may also be used to manage diabetes insipidus[4].

Recent Clinical Trials: Hydrochlorothiazide

A significant recent clinical trial involving HCTZ is the Diuretic Comparison Project (CSP 597) conducted by the VA Cooperative Studies Program. This pragmatic trial compared the effectiveness of HCTZ and chlorthalidone (CTD), another thiazide diuretic, in preventing cardiovascular disease and non-cancer death in Veterans with high blood pressure. The study found that both drugs were equally effective at lower doses, with no significant difference in outcomes such as heart attack, stroke, heart failure, or non-cancer death. However, there was a slight increase in the risk of low potassium levels in the CTD group, which was quickly resolved with potassium supplements[1].

Losartan Potassium: Mechanism and Uses

Losartan Potassium is an angiotensin II receptor antagonist (ARB) used to treat high blood pressure and protect the kidneys from damage due to diabetes. It works by blocking the action of angiotensin II, a potent vasoconstrictor, thereby reducing blood pressure and decreasing the workload on the heart[3].

Recent Clinical Trials: Losartan Potassium

A recent clinical trial investigated the efficacy of Losartan in hospitalized patients with COVID-19-induced acute lung injury. This randomized, placebo-controlled trial found that Losartan did not reduce lung injury or improve clinical outcomes such as ventilator-free days and mortality. Instead, it raised concerns about potential risks, including fewer vasopressor-free days in patients treated with Losartan[2].

Market Analysis

Hydrochlorothiazide

HCTZ is a well-established medication with a long history of use, first approved in 1959. It remains one of the most commonly prescribed diuretics for hypertension. According to Medicare data, in 2020, approximately 11.5 million people were prescribed HCTZ, making it a dominant player in the diuretic market. Despite clinical guidelines suggesting that chlorthalidone might be more effective, HCTZ's widespread use is due to its long-standing presence and perceived safety profile[1].

Losartan Potassium

Losartan Potassium is also widely used, particularly in combination with HCTZ. The combination of Losartan and HCTZ is often prescribed for patients who require both blood pressure reduction and diuretic therapy. The market for ARBs, including Losartan, is significant due to the high prevalence of hypertension and the need for effective blood pressure management. However, the recent trial results on Losartan's efficacy in COVID-19 patients may impact its usage in specific clinical contexts[2][3].

Projections

Hydrochlorothiazide

Given its long history and widespread use, HCTZ is expected to remain a staple in hypertension management. The recent VA study reinforces its effectiveness and safety profile, which will likely maintain its market position. However, ongoing research and new clinical trials may lead to adjustments in clinical guidelines and potentially affect its market share if other diuretics are found to be more effective or safer.

Losartan Potassium

The market for Losartan Potassium is expected to remain robust due to its established role in managing hypertension. However, the recent findings on its lack of efficacy in COVID-19 patients may lead to a reevaluation of its use in specific patient populations. This could result in a slight decline in its market share in those contexts but is unlikely to significantly impact its overall market position.

Side Effects and Safety Considerations

Both HCTZ and Losartan have well-documented side effects and safety considerations. HCTZ can cause electrolyte imbalances, low blood pressure, and other metabolic changes. It should be used with caution in patients with severe kidney disease and requires careful monitoring[4].

Losartan can lead to hypotension, tachycardia, and electrolyte imbalances, particularly in patients with renal impairment. The combination of Losartan with other RAS inhibitors is contraindicated in patients with moderate to severe renal impairment due to the risk of adverse outcomes[3].

Conclusion

Hydrochlorothiazide and Losartan Potassium remain crucial medications in the management of hypertension and related conditions. Recent clinical trials have provided valuable insights into their effectiveness and safety profiles. While HCTZ is expected to continue its dominant role in the diuretic market, Losartan's use may be refined based on new evidence, particularly in the context of COVID-19.

Key Takeaways

• Hydrochlorothiazide: Equally effective as chlorthalidone in preventing cardiovascular disease and non-cancer death at lower doses.
• Losartan Potassium: Did not reduce lung injury or improve clinical outcomes in COVID-19 patients.
• Market Position: HCTZ is expected to remain widely used, while Losartan's market may see adjustments based on new clinical evidence.
• Safety Considerations: Both drugs require careful monitoring for side effects, especially in patients with renal impairment.

FAQs

Q1: What is the primary mechanism of action of Hydrochlorothiazide? A1: Hydrochlorothiazide works by inhibiting the sodium-chloride cotransporter in the distal convoluted tubule of the kidney, leading to increased excretion of water and electrolytes.

Q2: What was the outcome of the VA study comparing Hydrochlorothiazide and Chlorthalidone? A2: The study found that both Hydrochlorothiazide and Chlorthalidone were equally effective in preventing cardiovascular disease and non-cancer death at lower doses.

Q3: Did Losartan reduce lung injury in COVID-19 patients in recent clinical trials? A3: No, Losartan did not reduce lung injury or improve clinical outcomes in hospitalized patients with COVID-19-induced acute lung injury.

Q4: What are the common side effects of Hydrochlorothiazide? A4: Common side effects include electrolyte imbalances, low blood pressure, and other metabolic changes.

Q5: Why is the combination of Losartan with other RAS inhibitors contraindicated in certain patients? A5: The combination is contraindicated in patients with moderate to severe renal impairment due to the risk of adverse outcomes such as hyperkalemia and renal failure.

Sources

1. VA's new "burden-free" study method finds two blood pressure drugs equally effective. VA Research Currents, December 15, 2022.
2. Efficacy of Losartan in Hospitalized Patients With COVID-19. JAMA Network Open, March 16, 2022.
3. Losartan Potassium and Hydrochlorothiazide Tablets. Health Canada, May 15, 2023.
4. Hydrochlorothiazide. Synapse, January 1, 2025.