Table of contents

• Clinical trial overview
• Studies in hypertension
• Studies in kidney disease
• Other patient groups and comparisons
• Trial phases and main endpoints
• Who participates in these studies

Clinical trial overview

The trial data show that Hydrochlorothiazide is being studied in several different settings, mainly around blood pressure and kidney-related care.^[1][2][3] The studies are interventional, which means researchers assign a treatment and then measure the results.^[1]

Most of the Hydrochlorothiazide research in this set is in people with hypertension, including primary hypertension, arterial hypertension, and uncontrolled hypertension with chronic kidney disease.^[1][3][4] There is also a Phase 1 study in healthy volunteers and a Phase 3 study in acute heart failure that includes Hydrochlorothiazide as one of the study drugs.^[5][6]

Studies in hypertension

Several trials focus on high blood pressure and ask whether Hydrochlorothiazide helps improve blood pressure control.^[1][3][4] One Phase 3 study in primary hypertension uses blood and urine biomarker profiles to predict which treatment group has a bigger drop in 24-hour blood pressure, including the Hydrochlorothiazide group.^[3]

Another completed study in arterial hypertension compared single-pill combinations that included Hydrochlorothiazide and measured the change in 24-hour systolic blood pressure, which is the top blood pressure number.^[4] The trial also looked at blood pressure variability and office blood pressure control, which means how much blood pressure changes over time and whether it is controlled during clinic visits.^[4]

A separate authorised study in difficult-to-treat hypertension evaluates current treatment, switching to triple single-pill combinations, and different add-on drug strategies, but Hydrochlorothiazide is not listed as an intervention in that trial data.^[1] It is included here only because the condition is closely related to the blood pressure research theme in this set.^[1]

Studies in kidney disease

Hydrochlorothiazide is also being studied in people with kidney disease, especially those with autosomal dominant polycystic kidney disease (ADPKD) and those with chronic kidney disease plus uncontrolled hypertension.^[2][5] In the HYDRO-PROTECT study, researchers are testing Hydrochlorothiazide together with tolvaptan and comparing it with placebo to see whether kidney function decline changes over time.^[2]

The main endpoint in HYDRO-PROTECT is the rate of kidney function decline, also called the eGFR slope, which measures how fast kidney function falls each year.^[2] The study also aims to learn about tolerability, including aquaresis, which means water loss in the urine, and quality of life.^[2]

In the THINK trial, Hydrochlorothiazide is one of several diuretic options being studied in patients with moderate to severe chronic kidney disease and uncontrolled hypertension.^[5] The main result is a time-to-event composite endpoint, which means the study follows patients until one of several serious outcomes happens, such as end-stage kidney disease, a large drop in eGFR, cardiovascular events, or death.^[5]

Other patient groups and comparisons

One Phase 3 study in hypertrophic cardiomyopathy compares Hydrochlorothiazide with valsartan in patients who also have arterial hypertension.^[6] The main outcome is the change in peak LVOT gradient at rest, which is a measure of how much blood flow is blocked out of the left side of the heart.^[6]

A Phase 3 study in acute heart failure includes Hydrochlorothiazide as one of the treatment options in a hospital setting.^[7] Its main endpoint is whether congestion is absent after the first 72 hours of intravenous diuretic treatment, using the ADVOR scale.^[7]

There is also a Phase 1 bioequivalence trial in healthy volunteers that compared two formulations of Hydrochlorothiazide.^[8] This type of study does not test disease treatment; it checks whether two products behave similarly in the body.^[8]

Trial phases and main endpoints

The Hydrochlorothiazide studies in this dataset include Phase 1, Phase 3, and low-intervention designs.^{[2][3][4][5][6][7]} Phase 1 appears in the bioequivalence study with healthy volunteers, while Phase 3 appears in the larger patient studies.^{[8][2][3][5][6][7]}

The main endpoints vary by study, but many are focused on blood pressure, kidney function, or clinical events.^{[2][3][4][5][6][7]} Examples include 24-hour blood pressure control, 24-hour systolic blood pressure change, eGFR slope, peak LVOT gradient, congestion resolution, and bioequivalence measures such as AUC and Cmax.^{[2][3][4][5][6][7][8]}

Who participates in these studies

The target populations are different across the trials, but they are clearly defined in the source data.^{[2][3][4][5][6][7][8]} They include adults with hypertension, patients with chronic kidney disease, people with ADPKD, patients with hypertrophic cardiomyopathy, people with acute heart failure, and healthy volunteers.^{[2][3][4][5][6][7][8]}

Some studies use placebo, which helps show whether the treatment really makes a difference, while others compare Hydrochlorothiazide with another active treatment or with a treatment strategy that includes several drugs.^[2][4][6]