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

NCT ID: NCT03928145

Last Updated: 2019-12-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-13
• Study Completion Date: 2021-07-31

Brief Summary

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.

Detailed 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).

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Chlorthalidone 25 mg + amiloride 20 mg

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

Group Type: EXPERIMENTAL

Chlorthalidone 25 mg

Intervention Type: DRUG

Chlorthalidone 25 mg taken orally in the morning for 12 weeks.

Amiloride 20 mg

Intervention Type: DRUG

Amiloride 20 mg taken orally in the morning for 12 weeks.

Chlorthalidone 25 mg + amiloride 10 mg

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

Group Type: ACTIVE_COMPARATOR

Chlorthalidone 25 mg

Intervention Type: DRUG

Chlorthalidone 25 mg taken orally in the morning for 12 weeks.

Amiloride 10 mg

Intervention Type: DRUG

Amiloride 10 mg taken orally in the morning for 12 weeks.

Hydrochlorothiazide 50 mg + amiloride 20 mg

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

Group Type: ACTIVE_COMPARATOR

Hydrochlorothiazide 50 mg

Intervention Type: DRUG

Hydrochlorothiazide 50 mg taken orally in the morning for 12 weeks.

Amiloride 20 mg

Intervention Type: DRUG

Amiloride 20 mg taken orally in the morning for 12 weeks.

Hydrochlorothiazide 50 mg + amiloride 10 mg

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

Group Type: ACTIVE_COMPARATOR

Hydrochlorothiazide 50 mg

Intervention Type: DRUG

Hydrochlorothiazide 50 mg taken orally in the morning for 12 weeks.

Amiloride 10 mg

Intervention Type: DRUG

Amiloride 10 mg taken orally in the morning for 12 weeks.

Interventions

Chlorthalidone 25 mg

Chlorthalidone 25 mg taken orally in the morning for 12 weeks.

Intervention Type: DRUG

Hydrochlorothiazide 50 mg

Hydrochlorothiazide 50 mg taken orally in the morning for 12 weeks.

Intervention Type: DRUG

Amiloride 20 mg

Amiloride 20 mg taken orally in the morning for 12 weeks.

Intervention Type: DRUG

Amiloride 10 mg

Amiloride 10 mg taken orally in the morning for 12 weeks.

Intervention Type: DRUG

Other Intervention Names

Chlorthalidone; Hydrochlorothiazide; Amiloride; Amiloride

Eligibility Criteria

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Cardiologia do Rio Grande do Sul

OTHER

Sponsor Role: collaborator

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Flavio Fuchs, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Clinicas de Porto Alegre

Locations

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Flavio Fuchs, MD, PhD

Role: CONTACT

ffuchs@hcpa.edu.br

+55 51 3359.8344

Facility Contacts

Flavio Fuchs, MD, PhD

Role: primary

ffuchs@hcpa.edu.br

+55 51 3359.8344

References

Martins VM, Helal L, Ferrari F, Bottino LG, Fuchs SC, Fuchs FD. Efficacy of chlorthalidone and hydrochlorothiazide in combination with amiloride in multiple doses on blood pressure in patients with primary hypertension: a protocol for a factorial randomized controlled trial. Trials. 2019 Dec 16;20(1):736. doi: 10.1186/s13063-019-3909-z.

Reference Type: DERIVED

PMID: 31843024 (View on PubMed)

Other Identifiers

2016-0553

Identifier Type: -

Identifier Source: org_study_id