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.
试验速览
- 阶段
- 3 期
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Mean change from baseline in 24-h systolic blood pressure measured by ABPM.
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
- •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.
研究组 & 干预措施
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.
干预措施: Chlorthalidone 25 mg (Drug)
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.
干预措施: Amiloride 20 mg (Drug)
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.
干预措施: Chlorthalidone 25 mg (Drug)
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.
干预措施: Amiloride 10 mg (Drug)
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.
干预措施: Hydrochlorothiazide 50 mg (Drug)
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.
干预措施: Amiloride 20 mg (Drug)
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.
干预措施: Hydrochlorothiazide 50 mg (Drug)
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.
干预措施: Amiloride 10 mg (Drug)
结局指标
主要结局
Mean change from baseline in 24-h systolic blood pressure measured by ABPM.
时间窗: 12 weeks
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.
时间窗: 12 weeks
Difference between the treatment arms in mean change from baseline in 24-h diastolic blood pressure measured by ABPM.
次要结局
- Mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure.(12 weeks)
- Mean change from baseline in LDL cholesterol (LDL-C).(12 weeks)
- Mean change from baseline in daytime and nighttime blood pressure measured by ABPM.(12 weeks)
- Proportion of participants reporting adverse events.(12 weeks)
- Mean change from baseline in total cholesterol.(12 weeks)
- Mean change from baseline in HDL cholesterol (HDL-C).(12 weeks)
- Mean change from baseline in triglycerides.(12 weeks)
- Mean change from baseline in creatinine.(12 weeks)
- Mean change from baseline in urea.(12 weeks)
- Mean change from baseline in potassium.(12 weeks)
- Mean change from baseline in sodium.(12 weeks)
- Mean change from baseline in magnesium.(12 weeks)
- Mean change from baseline in uric acid.(12 weeks)
- Mean change from baseline in fasting plasma glucose.(12 weeks)
- Mean change from baseline in hemoglobin A1c (HbA1c).(12 weeks)
- Proportion of participants achieving blood pressure control.(12 weeks.)