Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 63820 for:    Recruiting, Not yet recruiting, Available Studies
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03928145
Recruitment Status : Not yet recruiting
First Posted : April 25, 2019
Last Update Posted : April 25, 2019
Sponsor:
Collaborator:
Instituto de Cardiologia do Rio Grande do Sul
Information provided by (Responsible Party):
Hospital de Clinicas de Porto Alegre

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 Intervention/treatment Phase
Hypertension Drug: Chlorthalidone 25 mg Drug: Hydrochlorothiazide 50 mg Drug: Amiloride 20 mg Drug: Amiloride 10 mg 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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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)
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.
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.
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: Chlorthalidone

Drug: Amiloride 20 mg
Amiloride 20 mg taken orally in the morning for 12 weeks.
Other Name: 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 Name: Chlorthalidone

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

Drug: Amiloride 20 mg
Amiloride 20 mg taken orally in the morning for 12 weeks.
Other Name: Amiloride

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.
Other Name: Hydrochlorothiazide

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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   30 Years 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).
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03928145


Contacts
Layout table for location contacts
Contact: Flavio Fuchs, MD, PhD +55 51 3359.8344 ffuchs@hcpa.edu.br

Locations
Layout table for location information
Brazil
Hospital de Clinicas de Porto Alegre Not yet recruiting
Porto Alegre, RS, Brazil, 90035 903
Contact: Flavio Fuchs, MD, PhD    +55 51 3359.8344    ffuchs@hcpa.edu.br   
Sponsors and Collaborators
Hospital de Clinicas de Porto Alegre
Instituto de Cardiologia do Rio Grande do Sul
Investigators
Layout table for investigator information
Principal Investigator: Flavio Fuchs, MD, PhD Hospital de Clinicas de Porto Alegre

Layout table for additonal 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: April 25, 2019
Last Verified: April 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.

Layout table for additional information
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:
Hypertension
Treatment
Chlorthalidone
Hydrochlorothiazide
Amiloride

Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension
Essential Hypertension
Vascular Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Chlorthalidone
Amiloride
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Acid Sensing Ion Channel Blockers
Sodium Channel Blockers
Epithelial Sodium Channel Blockers
Diuretics, Potassium Sparing