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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/14/2021.

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

Clinicaltrials.gov identifier NCT03928145

Recruitment Status Recruiting

First Posted April 25, 2019

Last update posted December 9, 2019

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.

  • Condition or Disease:Hypertension
  • Intervention/Treatment: Drug: Chlorthalidone 25 mg
    Drug: Hydrochlorothiazide 50 mg
    Drug: Amiloride 20 mg
    Drug: Amiloride 10 mg
  • Phase: Phase 3
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 Design
  • Study Type: Interventional
  • Estimated Enrollment: 84 participants
  • Allocation: Randomized
  • Intervention Model: Factorial Assignment
  • Intervention 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Primary Purpose: Treatment
  • 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.
  • Actual Study Start Date: November 2019
  • Estimated Primary Completion Date: July 2021
  • Estimated Study Completion Date: July 2021
Arms and interventions
Arm Intervention/treatment
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.

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

Drug: Amiloride 20 mg
Amiloride 20 mg taken orally in the morning for 12 weeks.
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: Hydrochlorothiazide 50 mg
Hydrochlorothiazide 50 mg taken orally in the morning for 12 weeks.

Drug: Amiloride 10 mg
Amiloride 10 mg taken orally in the morning for 12 weeks.
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: Hydrochlorothiazide 50 mg
Hydrochlorothiazide 50 mg taken orally in the morning for 12 weeks.

Drug: Amiloride 20 mg
Amiloride 20 mg taken orally in the morning for 12 weeks.
Outcome Measures
  • Primary Outcome Measures: 1. 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.
  • 2. 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.
  • Secondary Outcome Measures: 1. 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.
  • 2. 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.
  • 3. Proportion of participants reporting adverse events. [ Time Frame: 12 weeks ]
    Difference between treatment arms in the proportion of participants reporting adverse events.
  • 4. 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.
  • 5. 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.
  • 6. 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.
  • 7. 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.
  • 8. 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.
  • 9. 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.
  • 10. 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.
  • 11. 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. 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.
  • 13. 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.
  • 14. 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.
  • 15. 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.
  • 16. 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.
Eligibility Criteria
  • Ages Eligible for Study: 30 to 75 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
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.

Contacts and Locations
Contacts

Contact: Flavio Fuchs, MD, PhD +55 51 3359.8344 ffuchs@hcpa.edu.br

Locations

Brazil, RS
Hospital de Clinicas de Porto Alegre
Porto Alegre

Sponsors and Collaborators

Hospital de Clinicas de Porto Alegre

Instituto de Cardiologia do Rio Grande do Sul

Investigators

Principal Investigator: Flavio Fuchs, MD, PhD Hospital de Clinicas de Porto Alegre

More Information
  • Responsible Party: Hospital de Clinicas de Porto Alegre
  • ClinicalTrials.gov Identifier: NCT03928145 History of Changes
  • Other Study ID Numbers: 2016-0553
  • First Posted: April 25, 2019 Key Record Dates
  • Last Update Posted: December 9, 2019
  • Last Verified: December 2019
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Yes
  • 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.
  • 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.
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Hospital de Clinicas de Porto Alegre: Hydrochlorothiazide
    Amiloride
    Treatment
    Hypertension
    Chlorthalidone
  • Additional relevant MeSH terms: Hypertension Essential Hypertension