Mechanisms of Diuretic Resistance in Heart Failure, Aim 2
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Correlation between distal sodium reabsorption and uEV pendrin/CD9
研究概览
简要总结
Randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.
详细描述
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.
Patients will be co-enrolled in this study and an ancillary study for administration of Bendroflumethiazide. Administration of bendroflumethiazide will take place under an ancillary protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Clinical diagnosis of HF
- •No plan for titration/change of heart failure medical or device therapies during the study period.
- •Absence of non-elective hospitalizations in the previous 2 weeks
- •At optimal volume status by symptoms, exam, and dry weight.
- •Serum potassium ≤ 5.0 mmol/L
- •Serum sodium ≥ 130 mEq/L
- •Age > 18 years
- •Hemoglobin ≥8 g/dL
- •Objective evidence of diuretic resistance to a 10mg bumetanide challenge, defined as:
- •FENa <10% and total sodium output <150mmol and
- •At least one of the following criteria:
- •1. Chronic home furosemide dose > or equal to 80mg furosemide equivalents daily
- •eGFR < 60ml/min
- •Serum chloride <100mmol/L
- •FENa <5% and total sodium output <75mmol on the 2 hour screening
排除标准
- •GFR <20 ml/min/1.73m2 using the CKD-EPI equation or use of renal replacement therapies
- •Use of any non-loop type diuretic in the last 7 days or 5 half lives, with the exclusion of low dose aldosterone antagonist (e.g., spironolactone or eplerenone ≤50 mg). Examples of non-loop diuretics include but may not be limited to acetazolamide (oral or IV, not ophthalmic), metolazone, HCTZ, chlorthalidone, chlorothiazide, indapamide, triamterene, amiloride, finerenone, spironolactone dose > 50mg day, eplerenone > 50mg/day,
- •History of flash pulmonary edema requiring hospitalization and treatment with biphasic positive airway pressure or mechanical ventilation or a "brittle" volume sensitive HF phenotype such as an infiltrative or restrictive cardiomyopathy (i.e. amyloid cardiomyopathy, etc).
- •Hemoglobin < 8 g/dL or symptomatic anemia
- •Pregnant or breastfeeding
- •Inability to give written informed consent or comply with study protocol or follow-up visits
- •Chronic urinary retention limiting ability to perform timed urine collection procedures
- •On Lithium therapy
- •On pimozide or thioridazine
- •Diagnosis of liver failure
- •Contraindications or allergy to sulfonamides
- •Any contraindication to thiazide diuretic or allergy to thiazide or bendroflumethiazide
研究组 & 干预措施
Placebo/ Placebo
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21
干预措施: Placebo (Drug)
Placebo/ Amiloride
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21
干预措施: Placebo (Drug)
Placebo/ Amiloride
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21
干预措施: Amiloride (Drug)
Bendroflumethiazide/ Amiloride
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21
干预措施: Amiloride (Drug)
Placebo/ Bendroflumethiazide
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21
干预措施: Placebo (Drug)
Placebo/ Bendroflumethiazide
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21
干预措施: Bendroflumethiazide (Drug)
Bendroflumethiazide/ Amiloride
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21
干预措施: Bendroflumethiazide (Drug)
结局指标
主要结局
Correlation between distal sodium reabsorption and uEV pendrin/CD9
时间窗: 21 days
Correlation between distal sodium reabsorption (FELi minus FENa) and uEV pendrin/CD9
Change in peak FENa from bumetanide monotherapy to bumetanide plus combination therapy
时间窗: 21 days
Change in peak FENa from bumetanide monotherapy to bumetanide plus combination therapy
Change in distal sodium reabsorption
时间窗: 21 days
Change in distal sodium reabsorption (FELi minus FENa) from bumetanide monotherapy to bumetanide plus combination therapy
次要结局
未报告次要终点
研究者
Jeffrey Testani
Associate Professor of Medicine
Yale University