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

Primary Purpose

Hypertension

Status
Unknown status
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
Chlorthalidone 25 mg
Hydrochlorothiazide 50 mg
Amiloride 20 mg
Amiloride 10 mg
Sponsored by
Hospital de Clinicas de Porto Alegre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension focused on measuring Hypertension, Treatment, Chlorthalidone, Hydrochlorothiazide, Amiloride

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Hospital de Clinicas de Porto AlegreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Active Comparator

Active Comparator

Arm Label

Chlorthalidone 25 mg + amiloride 20 mg

Chlorthalidone 25 mg + amiloride 10 mg

Hydrochlorothiazide 50 mg + amiloride 20 mg

Hydrochlorothiazide 50 mg + amiloride 10 mg

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Mean change from baseline in daytime and nighttime blood pressure measured by ABPM.
Difference between the treatment arms in 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.
Difference between the treatment arms in mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure.
Proportion of participants reporting adverse events.
Difference between treatment arms in the proportion of participants reporting adverse events.
Mean change from baseline in total cholesterol.
Difference between the treatment arms in mean change from baseline in serum total cholesterol, measured in mg/dL.
Mean change from baseline in HDL cholesterol (HDL-C).
Difference between the treatment arms in mean change from baseline in serum HDL cholesterol (HDL-C), measured in mg/dL.
Mean change from baseline in LDL cholesterol (LDL-C).
Difference between the treatment arms in mean change from baseline in serum LDL cholesterol (LDL-C), measured in mg/dL.
Mean change from baseline in triglycerides.
Difference between the treatment arms in mean change from baseline in serum triglycerides, measured in mg/dL.
Mean change from baseline in creatinine.
Difference between the treatment arms in mean change from baseline in serum creatinine, measured in mg/dL.
Mean change from baseline in urea.
Difference between the treatment arms in mean change from baseline in serum urea, measured in mg/dL.
Mean change from baseline in potassium.
Difference between the treatment arms in mean change from baseline in serum potassium, measured in mEq/L.
Mean change from baseline in sodium.
Difference between the treatment arms in mean change from baseline in serum sodium, measured in mg/dL.
Mean change from baseline in magnesium.
Difference between the treatment arms in mean change from baseline in serum magnesium, measured in mg/dL.
Mean change from baseline in uric acid.
Difference between the treatment arms in mean change from baseline in serum uric acid, measured in mg/dL.
Mean change from baseline in fasting plasma glucose.
Difference between the treatment arms in mean change from baseline in fasting plasma glucose, measured in mg/dL.
Mean change from baseline in hemoglobin A1c (HbA1c).
Difference between the treatment arms in mean change from baseline in hemoglobin A1c (HbA1c), measured in percentage.
Proportion of participants achieving blood pressure control.
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.

Full Information

First Posted
April 22, 2019
Last Updated
December 6, 2019
Sponsor
Hospital de Clinicas de Porto Alegre
Collaborators
Instituto de Cardiologia do Rio Grande do Sul
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1. Study Identification

Unique Protocol Identification Number
NCT03928145
Brief Title
Efficacy of Chlorthalidone and Hydrochlorothiazide Combined With Amiloride on Blood Pressure in Primary Hypertension.
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 13, 2019 (Actual)
Primary Completion Date
July 2021 (Anticipated)
Study Completion Date
July 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital de Clinicas de Porto Alegre
Collaborators
Instituto de Cardiologia do Rio Grande do Sul

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Hypertension, Treatment, Chlorthalidone, Hydrochlorothiazide, Amiloride

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Model Description
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Chlorthalidone 25 mg + amiloride 20 mg
Arm Type
Experimental
Arm Description
Chlorthalidone 25 mg plus amiloride 20 mg combined in a single capsule, taken orally in the morning, for 12 weeks.
Arm Title
Chlorthalidone 25 mg + amiloride 10 mg
Arm Type
Active Comparator
Arm Description
Chlorthalidone 25 mg plus amiloride 10 mg combined in a single capsule, taken orally in the morning, for 12 weeks.
Arm Title
Hydrochlorothiazide 50 mg + amiloride 20 mg
Arm Type
Active Comparator
Arm Description
Hydrochlorothiazide 50 mg plus amiloride 20 mg combined in a single capsule, taken orally in the morning, for 12 weeks.
Arm Title
Hydrochlorothiazide 50 mg + amiloride 10 mg
Arm Type
Active Comparator
Arm Description
Hydrochlorothiazide 50 mg plus amiloride 10 mg combined in a single capsule, taken orally in the morning, for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Chlorthalidone 25 mg
Other Intervention Name(s)
Chlorthalidone
Intervention Description
Chlorthalidone 25 mg taken orally in the morning for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Hydrochlorothiazide 50 mg
Other Intervention Name(s)
Hydrochlorothiazide
Intervention Description
Hydrochlorothiazide 50 mg taken orally in the morning for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Amiloride 20 mg
Other Intervention Name(s)
Amiloride
Intervention Description
Amiloride 20 mg taken orally in the morning for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Amiloride 10 mg
Other Intervention Name(s)
Amiloride
Intervention Description
Amiloride 10 mg taken orally in the morning for 12 weeks.
Primary Outcome Measure Information:
Title
Mean change from baseline in 24-h systolic blood pressure measured by ABPM.
Description
Difference between the treatment arms in mean change from baseline in 24-h systolic blood pressure measured by ABPM.
Time Frame
12 weeks
Title
Mean change from baseline in 24-h diastolic blood pressure measured by ABPM.
Description
Difference between the treatment arms in mean change from baseline in 24-h diastolic blood pressure measured by ABPM.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Mean change from baseline in daytime and nighttime blood pressure measured by ABPM.
Description
Difference between the treatment arms in mean change from baseline in daytime and nighttime systolic and diastolic blood pressure measured by ABPM.
Time Frame
12 weeks
Title
Mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure.
Description
Difference between the treatment arms in mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure.
Time Frame
12 weeks
Title
Proportion of participants reporting adverse events.
Description
Difference between treatment arms in the proportion of participants reporting adverse events.
Time Frame
12 weeks
Title
Mean change from baseline in total cholesterol.
Description
Difference between the treatment arms in mean change from baseline in serum total cholesterol, measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in HDL cholesterol (HDL-C).
Description
Difference between the treatment arms in mean change from baseline in serum HDL cholesterol (HDL-C), measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in LDL cholesterol (LDL-C).
Description
Difference between the treatment arms in mean change from baseline in serum LDL cholesterol (LDL-C), measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in triglycerides.
Description
Difference between the treatment arms in mean change from baseline in serum triglycerides, measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in creatinine.
Description
Difference between the treatment arms in mean change from baseline in serum creatinine, measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in urea.
Description
Difference between the treatment arms in mean change from baseline in serum urea, measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in potassium.
Description
Difference between the treatment arms in mean change from baseline in serum potassium, measured in mEq/L.
Time Frame
12 weeks
Title
Mean change from baseline in sodium.
Description
Difference between the treatment arms in mean change from baseline in serum sodium, measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in magnesium.
Description
Difference between the treatment arms in mean change from baseline in serum magnesium, measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in uric acid.
Description
Difference between the treatment arms in mean change from baseline in serum uric acid, measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in fasting plasma glucose.
Description
Difference between the treatment arms in mean change from baseline in fasting plasma glucose, measured in mg/dL.
Time Frame
12 weeks
Title
Mean change from baseline in hemoglobin A1c (HbA1c).
Description
Difference between the treatment arms in mean change from baseline in hemoglobin A1c (HbA1c), measured in percentage.
Time Frame
12 weeks
Title
Proportion of participants achieving blood pressure control.
Description
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.
Time Frame
12 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Flavio Fuchs, MD, PhD
Phone
+55 51 3359.8344
Email
ffuchs@hcpa.edu.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Flavio Fuchs, MD, PhD
Organizational Affiliation
Hospital de Clinicas de Porto Alegre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital de Clinicas de Porto Alegre
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90035 903
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Flavio Fuchs, MD, PhD
Phone
+55 51 3359.8344
Email
ffuchs@hcpa.edu.br

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
31843024
Citation
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.
Results Reference
derived

Learn more about this trial

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

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