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

December 6, 2019 updated by: Hospital de Clinicas de Porto Alegre

Efficacy of Chlorthalidone and Hydrochlorothiazide in Combination With Amiloride in Multiple Doses on Blood Pressure in Patients With Primary Hypertension: a Factorial Randomized Controlled Trial.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
84

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Brazil
    • RS
      • Porto Alegre, RS, Brazil, 90035 903
        • Recruiting
        • Hospital de Clínicas de Porto Alegre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Chlorthalidone 25 mg
Chlorthalidone 25 mg taken orally in the morning for 12 weeks.
Other Names:
  • Chlorthalidone
Drug: Amiloride 20 mg
Amiloride 20 mg taken orally in the morning for 12 weeks.
Other Names:
  • Amiloride
Active Comparator: 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.
Drug: Chlorthalidone 25 mg
Chlorthalidone 25 mg taken orally in the morning for 12 weeks.
Other Names:
  • Chlorthalidone
Drug: Amiloride 10 mg
Amiloride 10 mg taken orally in the morning for 12 weeks.
Other Names:
  • Amiloride
Active Comparator: 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.
Drug: Amiloride 20 mg
Amiloride 20 mg taken orally in the morning for 12 weeks.
Other Names:
  • Amiloride
Drug: Hydrochlorothiazide 50 mg
Hydrochlorothiazide 50 mg taken orally in the morning for 12 weeks.
Other Names:
  • Hydrochlorothiazide
Active Comparator: 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.
Drug: Amiloride 10 mg
Amiloride 10 mg taken orally in the morning for 12 weeks.
Other Names:
  • Amiloride
Drug: Hydrochlorothiazide 50 mg
Hydrochlorothiazide 50 mg taken orally in the morning for 12 weeks.
Other Names:
  • Hydrochlorothiazide

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean change from baseline in 24-h systolic blood pressure measured by ABPM.
Time Frame: 12 weeks
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.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in 24-h diastolic blood pressure measured by ABPM.
12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean change from baseline in daytime and nighttime blood pressure measured by ABPM.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in daytime and nighttime systolic and diastolic blood pressure measured by ABPM.
12 weeks
Mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure.
12 weeks
Proportion of participants reporting adverse events.
Time Frame: 12 weeks
Difference between treatment arms in the proportion of participants reporting adverse events.
12 weeks
Mean change from baseline in total cholesterol.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum total cholesterol, measured in mg/dL.
12 weeks
Mean change from baseline in HDL cholesterol (HDL-C).
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum HDL cholesterol (HDL-C), measured in mg/dL.
12 weeks
Mean change from baseline in LDL cholesterol (LDL-C).
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum LDL cholesterol (LDL-C), measured in mg/dL.
12 weeks
Mean change from baseline in triglycerides.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum triglycerides, measured in mg/dL.
12 weeks
Mean change from baseline in creatinine.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum creatinine, measured in mg/dL.
12 weeks
Mean change from baseline in urea.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum urea, measured in mg/dL.
12 weeks
Mean change from baseline in potassium.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum potassium, measured in mEq/L.
12 weeks
Mean change from baseline in sodium.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum sodium, measured in mg/dL.
12 weeks
Mean change from baseline in magnesium.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum magnesium, measured in mg/dL.
12 weeks
Mean change from baseline in uric acid.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in serum uric acid, measured in mg/dL.
12 weeks
Mean change from baseline in fasting plasma glucose.
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in fasting plasma glucose, measured in mg/dL.
12 weeks
Mean change from baseline in hemoglobin A1c (HbA1c).
Time Frame: 12 weeks
Difference between the treatment arms in mean change from baseline in hemoglobin A1c (HbA1c), measured in percentage.
12 weeks
Proportion of participants achieving blood pressure control.
Time Frame: 12 weeks.
Difference between treatment arms in the proportion of participants achieving blood pressure control. Blood pressure control will be defined as <140/90 mmHg and <130/80 mmHg for office BP and 24-h ABPM, respectively.
12 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospital de Clinicas de Porto Alegre

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Instituto de Cardiologia do Rio Grande do Sul

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Flavio Fuchs, MD, PhD, Hospital de Clínicas de Porto Alegre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 13, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 22, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 25, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 9, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2016-0553

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

This trial is in accordance with the compliance of the reproducibility standards accordingly to the International Committee of Medical Journal Editors (ICMJE). The investigators intend to publish the results in an open-access journal, indexed at the Directory of Open Access Journals, with the copyrights transferred to the authors (CC By 4.0). Also, all materials, raw and treated data, statistical code and outputs will be publicly shared without restrictions to access the data neither expiration date. The repository was not chosen yet and will be provided in further amendments or in the final report of this study. All laboratory specimens, reports, data collection, process, and administrative forms will be identified by a coded identification number to maintain participant confidentiality. After full data analysis, all subject identifiers will be erased.

IPD Sharing Time Frame

The individual participant dataset will become available at a public repository up to six months after the first study publication.

IPD Sharing Access Criteria

A simple registration will grant access to study datasets. The website for these files is not defined at the time of registration.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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