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

NCT03928145 | Unknown Phase 3

• 1 other identifier: 2016-0553
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

Hypertension; Treatment; Chlorthalidone; Hydrochlorothiazide; Amiloride

Outcome Measures

Primary Outcomes (2)

• Mean change from baseline in 24-h systolic blood pressure measured by ABPM.

  Difference between the treatment arms in mean change from baseline in 24-h systolic blood pressure measured by ABPM.

  12 weeks

• Mean change from baseline in 24-h diastolic blood pressure measured by ABPM.

  Difference between the treatment arms in mean change from baseline in 24-h diastolic blood pressure measured by ABPM.

  12 weeks

Secondary Outcomes (16)

• Mean change from baseline in daytime and nighttime blood pressure measured by ABPM.

  12 weeks

• Mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure.

  12 weeks

• Proportion of participants reporting adverse events.

  12 weeks

• Mean change from baseline in total cholesterol.

  12 weeks

• Mean change from baseline in HDL cholesterol (HDL-C).

  12 weeks

Study Arms (4)

Chlorthalidone 25 mg + amiloride 20 mg

EXPERIMENTAL

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

Drug: Chlorthalidone 25 mg; Drug: Amiloride 20 mg

Chlorthalidone 25 mg + amiloride 10 mg

ACTIVE COMPARATOR

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

Drug: Chlorthalidone 25 mg; Drug: Amiloride 10 mg

Hydrochlorothiazide 50 mg + amiloride 20 mg

ACTIVE COMPARATOR

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

Drug: Hydrochlorothiazide 50 mg; Drug: Amiloride 20 mg

Hydrochlorothiazide 50 mg + amiloride 10 mg

ACTIVE COMPARATOR

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

Drug: Hydrochlorothiazide 50 mg; Drug: Amiloride 10 mg

Interventions

Chlorthalidone 25 mg DRUG

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

Also known as: Chlorthalidone

Chlorthalidone 25 mg + amiloride 10 mg; Chlorthalidone 25 mg + amiloride 20 mg

Hydrochlorothiazide 50 mg DRUG

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

Also known as: Hydrochlorothiazide

Hydrochlorothiazide 50 mg + amiloride 10 mg; Hydrochlorothiazide 50 mg + amiloride 20 mg

Amiloride 20 mg DRUG

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

Also known as: Amiloride

Chlorthalidone 25 mg + amiloride 20 mg; Hydrochlorothiazide 50 mg + amiloride 20 mg

Amiloride 10 mg DRUG

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

Also known as: Amiloride

Chlorthalidone 25 mg + amiloride 10 mg; Hydrochlorothiazide 50 mg + amiloride 10 mg

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• Instituto de Cardiologia do Rio Grande do Sul: collaborator

Study Sites (1)

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035 903, Brazil

RECRUITING

Related Publications (1)

• 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.

  PMID: 31843024 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Chlorthalidone; Hydrochlorothiazide; Amiloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Sulfones; Sulfur Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Thiazides; Pyrazines; Heterocyclic Compounds, 1-Ring

Study Officials

• Flavio Fuchs, MD, PhD

  Hospital de Clinicas de Porto Alegre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Flavio Fuchs, MD, PhD

CONTACT

+55 51 3359.8344; ffuchs@hcpa.edu.br

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study medication will have the same color, taste, consistency, odor and appearance. In this way, patients, care providers, outcome assessors and the entire research team will be blinded regarding the allocation to the treatment groups throughout the study.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The trial has a factorial design, where participants will receive two simultaneous interventions: a thiazide diuretic (chlorthalidone 25 mg or hydrochlorothiazide 50 mg) and a potassium-sparing diuretic (amiloride 10 mg or amiloride 20 mg). Randomization will be done in 1:1:1:1 ratio, and participants will be randomly assigned to four groups: a) chlorthalidone 25 mg + amiloride 10 mg; b) chlorthalidone 25 mg + amiloride 20 mg; c) hydrochlorothiazide 50 mg + amiloride 10 mg; and d) hydrochlorothiazide 50 mg + amiloride 20 mg.

Study Record Dates

• First Submitted: April 22, 2019
• First Posted: April 25, 2019
• Study Start: November 13, 2019
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: December 9, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: The individual participant dataset will become available at a public repository up to six months after the first study publication.
• Access Criteria: A simple registration will grant access to study datasets. The website for these files is not defined at the time of registration.

Locations

BR (1)