Efficacy of Chlorthalidone and Hydrochlorothiazide Combined With Amiloride on Blood Pressure in Primary Hypertension.

Hospital de Clinicas de Porto Alegre

Status and phase: Unknown; Phase 3

Conditions: Hypertension

Treatments: Drug: Amiloride 10 mg; Drug: Hydrochlorothiazide 50 mg; Drug: Amiloride 20 mg; Drug: Chlorthalidone 25 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03928145

2016-0553

Details and patient eligibility

About

Thiazide diuretics have demonstrated favorable blood pressure lowering efficacy, safety profile and low cost, but it is still unclear what are the equivalence of doses of their more common agents, chlorthalidone and hydrochlorothiazide. Besides, concernments about adverse metabolic effects such as hypokalemia, hyperglycemia and hyperlipidemia do exist, which may be attenuated with the concomitant administration of a potassium-sparing diuretic, such as amiloride. In addition to control adverse effects of thiazides, amiloride could offer an additional blood pressure lowering effect, but the efficacy of different doses was not fully established. This study aims to investigate the blood pressure lowering efficacy of chlorthalidone and hydrochlorothiazide, in combination with amiloride in different doses, for the initial management in patients with primary hypertension.

Full description

This is a factorial (2x2) randomized double-blinded clinical trial comparing the association of a thiazide diuretic (chlorthalidone 25 mg/day or hydrochlorothiazide 50 mg/day) with a potassium-sparing diuretic (amiloride 10 mg/day or amiloride 20 mg/day) as first drug option in patients aged 30 to 75 years with primary hypertension. The thiazide diuretic and amiloride will be combined in a single capsule. The capsules will be of the same size and color, so that neither the researcher nor the patients can distinguish the treatment by their appearance. The primary outcome will be the mean change from baseline in 24-h systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM). The secondary outcomes will be the mean change from baseline in daytime and nighttime systolic and diastolic blood pressure measured by ABPM, mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure, incidence of adverse events, variation of laboratory parameters and proportion of patients who achieved blood pressure control (<140/90 mmHg and <130/80 mmHg for office blood pressure and 24-h ABPM, respectively). The follow-up will last 12 weeks. For a P alpha of 0.05, power of 80%, and standard deviation of 9 mmHg, and absolute difference of 6 mmHg on systolic blood pressure on 24-h ABPM, it will be necessary to study a total of 76 patients. The sample size will be increased by 10% to compensate losses, resulting in 84 patients being randomized in total (42 for each arm).

Enrollment: 84 estimated patients

Sex: All

Ages: 30 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults (age 30 to 75 years).
• Diagnosis of primary hypertension based on ABPM (mean 24-h systolic BP ≥130 mmHg or mean 24-h diastolic BP ≥80 mmHg).
• No current use of antihypertensive medication.

Exclusion criteria

• Low life expectancy.
• Other indications for the use of diuretics.
• Intolerance or contraindications to the study drugs.
• Cardiovascular disease (heart failure, myocardial infarction or stroke).
• Secondary hypertension.
• Chronic kidney disease and / or abnormal renal function (creatinine >1.5 mg/dL).
• Hyperkalemia (serum potassium >5.5 mEq/L).
• Gout.
• Previous antihypertensive treatment with more than one drug.
• Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg measured through office blood pressure.
• Pregnancy or prospective pregnancy during the study.
• Lactating women.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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84 participants in 4 patient groups

Chlorthalidone 25 mg + amiloride 20 mg

Experimental group

Description:

Chlorthalidone 25 mg plus amiloride 20 mg combined in a single capsule, taken orally in the morning, for 12 weeks.

Treatment:

Drug: Chlorthalidone 25 mg

Drug: Amiloride 20 mg

Chlorthalidone 25 mg + amiloride 10 mg

Active Comparator group

Description:

Chlorthalidone 25 mg plus amiloride 10 mg combined in a single capsule, taken orally in the morning, for 12 weeks.

Treatment:

Drug: Chlorthalidone 25 mg

Drug: Amiloride 10 mg

Hydrochlorothiazide 50 mg + amiloride 20 mg

Active Comparator group

Description:

Hydrochlorothiazide 50 mg plus amiloride 20 mg combined in a single capsule, taken orally in the morning, for 12 weeks.

Treatment:

Drug: Amiloride 20 mg

Drug: Hydrochlorothiazide 50 mg

Hydrochlorothiazide 50 mg + amiloride 10 mg

Active Comparator group

Description:

Hydrochlorothiazide 50 mg plus amiloride 10 mg combined in a single capsule, taken orally in the morning, for 12 weeks.

Treatment:

Drug: Hydrochlorothiazide 50 mg

Drug: Amiloride 10 mg