Safety and Efficacy of the Combination of Loop Diuretics With Thiazide-type Diuretics in Patients With Decompensated Heart Failure: a Double-blind, Randomized, Placebo-controlled Trial (CLOROTIC Trial).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 232
- 试验地点
- 1
- 主要终点
- Patient-reported dyspnea
研究概览
简要总结
The purpose of this study is to determine whether a combined diuretic therapy (loop diuretics with thiazide-type diuretics) is more effective (in terms of improving fluid overload symptoms) among patients with decompensated heart failure in comparison with loop diuretic alone.
详细描述
Volume overload is an important clinical target in heart failure management, typically addressed using loop diuretics. An important and challenging subset of heart failure patients exhibit fluid overload despite significant doses of loop diuretics. One approach to overcome loop diuretic resistance is the addition of a thiazide-type diuretic to produce diuretic synergy via "sequential nephron blockade," first described more than 40 years ago. Although potentially able to induce diuresis in patients otherwise resistant to high doses of loop diuretics, this strategy has not been subjected to large-scale clinical trials to establish safety and clinical efficacy. Combination diuretic therapy using any of several thiazide-type diuretics can more than double daily urine sodium excretion to induce weight loss and edema resolution. To our knowledge there are no clinical trials designed to prove the efficacy and safety of combined diuretic therapy (a commonly used therapy) among patients with decompensated heart failure.
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
- •History of chronic heart failure
- •Admission for acute decompensated heart failure
- •There is no prespecified inclusion criterion with respect to heart failure etiology and/or ejection fraction
- •Receipt of an oral loop diuretic for at least 1 month before hospitalization, at a dose between 80 mg and 240 mg daily in the case of furosemide and an equivalent dose in the case of a different loop diuretic (20 mg of torasemide or 1 mg of bumetanide was considered to be equivalent to 40 mg of furosemide)
排除标准
- •Other etiologies of fluid overload different from heart failure
- •Hyponatremia: any symptomatic sodium value or a sodium level below 125mmol/l
- •Unstable patients: acute coronary syndrome, cardiogenic shock or ICU admission.
- •Patients requiring inotropic agents or renal replacement therapies
- •Life expectancy < 6 months
- •Prior treatment with thiazide-type diuretics
- •Aldosterone antagonists are permitted if the patient had been taking them on a long-term basis (at least 30 days before randomisation)
- •Pregnancy or breastfeeding period
- •Active alcoholism and/or other substance abuse
研究组 & 干预措施
Loop plus thiazide-type diuretic
Loop diuretic plus hydrochlorothiazide
干预措施: hydrochlorothiazide (Drug)
Loop diuretic plus placebo
Loop diuretic plus placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Patient-reported dyspnea
时间窗: Patient-reported dyspnea is assessed every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.
Patient-reported dyspnea is assessed every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge. Patient-reported dyspnea is assessed with the use of a visual-analogue scale (VAS) and the Linker 7 point scale. Changes in patient-reported dyspnea: changes in the dyspnea scales from baseline to the 5th day of hospitalisation.
Changes in body weight
时间窗: Bodyweight will be measured every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.
Bodyweight will be measured every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge. Changes in body weight measurements: the mean of weight lost every 24 hours and the total weight lost from baseline to the 5th day of hospitalisation. Participants will be followed for the duration of hospital stay, an expected average of 9 days.
次要结局
- Metrics of diuretic response(weight loss and net fluid loss per mg of furosemide)
- Rehospitalization (all-cause and heart failure)(Rehospitalization (all-cause and heart failure) at 30 and 90days post-discharge)
- Diuresis(24-hour diuresis will be quantified every 24 hours (during hospitalisation) from the 1st day until the 4th day of hospitalisation.)
- Worsening renal function(Renal function will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.)
- Changes in electrolyte levels (sodium and potassium)(Electrolyte levels (sodium and potassium) will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.)
- Mortality (all-cause and heart failure)(Mortality (all-cause and heart failure) at 30 and 90days post-discharge)
研究者
Joan Carles Trullas Vila
Principal Investigator
Spanish Society of Internal Medicine