Chlorthalidone in Chronic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Change From Baseline to 12 Weeks in Systolic Ambulatory Blood Pressure in the Chlorthalidone Group Compared to Placebo.
研究概览
简要总结
It is estimated that in the United States there are approximately 8 million individuals who have moderate to severe chronic kidney disease (CKD). Among them hypertension is common and is often poorly controlled due to an expanded volume state; diuretics are frequently prescribed. Loop diuretics are potent and effective in lowering blood pressure (BP) but their use is associated with acute kidney injury. Thiazide diuretics, on the other hand, are less potent, their use may be associated with less acute kidney injury, but as yet there are no firm data to support that thiazide diuretic therapy can improve BP among subjects with advanced CKD. The investigators found 13 studies on the use of thiazide diuretics in advanced CKD either alone or in combination with loop diuretics and concluded that thiazides may be useful. Thiazides cause a negative Na balance, increase Na excretion by 10-15% and weight loss by 1-2 kg in observational studies. Observational data show that thiazides lead to an improvement in seated clinic BP of about 10-15 mmHg systolic and 5-10 mmHg diastolic whereas randomized trials show about a 15 mmHg reduction in mean BP. Randomized trials had only between 7 and 23 subjects each; accordingly, larger studies are needed to evaluate their safety and efficacy in moderate to advanced CKD.
详细描述
This is a placebo-controlled, double-blind, randomized controlled trial of chlorthalidone (CTD) in patients with CKD and poorly controlled hypertension
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than 18 years.
- •Calculated glomerular filtration rate (GFR) by 4-component Modification of Diet in Renal Disease (MDRD) formula < 30 ml/min/1.73m2 but ≥15 mL/min/1.73m
- •The hospital laboratory uses isotope dilution mass spectrometry (IDMS) calibrated creatinine and the appropriate formula is used to estimate GFR.
- •Hypertension. This is defined as BP of either ≥130 systolic or ≥80 mmHg by 24-hour ambulatory BP monitoring.
- •Treatment with antihypertensive drugs: This would require the use of at least one antihypertensive drug. One of the drugs should be either an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). If these are contraindicated then use of a beta-blocker is required prior to randomization.
排除标准
- •Use of thiazide or thiazide-like drugs in the previous 12 weeks.
- •Use of furosemide in a dose >200 mg/d.
- •BP of either ≥160 systolic or ≥100 mmHg by 24-hour ambulatory BP monitoring.
- •Expected to receive renal replacement therapy within the next 3 months.
- •Myocardial infarction, heart failure hospitalization, or stroke ≤3 months prior to randomization.
- •Pregnant or breastfeeding women or women who are planning to become pregnant or those not using a reliable form of contraception (oral contraceptives. condoms and diaphragms will be considered reliable).
- •Known hypersensitivity to thiazide or sulfa drugs.
- •Organ transplant recipient or therapy with immunosuppressive agents.
研究组 & 干预措施
Chlorthalidone
Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results.
干预措施: Chlorthalidone (Drug)
Placebo
Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to 12 Weeks in Systolic Ambulatory Blood Pressure in the Chlorthalidone Group Compared to Placebo.
时间窗: Baseline to 12 weeks
次要结局
- Changes in Albuminuria From Baseline at Each 4 Week Visit in the Log Transformed Albumin/Creatinine Ratio in the Chlorthalidone Group Compared to Placebo(Baseline to 12 weeks)
- Change From Baseline at Each 4 Week Visit in Log of Aldosterone and Log of Renin in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons.(Baseline to 12 weeks)
- Change From Baseline at Each 4 Week Visit in Log of N-terminal Pro B-type Natriuretic Peptide (NTproBNP) in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons.(Baseline to 12 weeks)
- Change From Baseline at Each 4 Week Visit in Body Volume in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons.(Baseline to 12 weeks)
研究者
Rajiv Agarwal
Professor of Medicine
Indiana University