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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
84
Chlorthalidone 25 mg taken orally in the morning for 12 weeks.
Hydrochlorothiazide 50 mg taken orally in the morning for 12 weeks.
Amiloride 20 mg taken orally in the morning for 12 weeks.
Amiloride 10 mg taken orally in the morning for 12 weeks.
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
RECRUITINGMean 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.
Time frame: 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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
Proportion of participants reporting adverse events.
Difference between treatment arms in the proportion of participants reporting adverse events.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
Mean change from baseline in triglycerides.
Difference between the treatment arms in mean change from baseline in serum triglycerides, measured in mg/dL.
Time frame: 12 weeks
Mean change from baseline in creatinine.
Difference between the treatment arms in mean change from baseline in serum creatinine, measured in mg/dL.
Time frame: 12 weeks
Mean change from baseline in urea.
Difference between the treatment arms in mean change from baseline in serum urea, measured in mg/dL.
Time frame: 12 weeks
Mean change from baseline in potassium.
Difference between the treatment arms in mean change from baseline in serum potassium, measured in mEq/L.
Time frame: 12 weeks
Mean change from baseline in sodium.
Difference between the treatment arms in mean change from baseline in serum sodium, measured in mg/dL.
Time frame: 12 weeks
Mean change from baseline in magnesium.
Difference between the treatment arms in mean change from baseline in serum magnesium, measured in mg/dL.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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.
Time frame: 12 weeks.
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