Renal Mechanistic Effects of Acute and Chronic Empagliflozin in Heart Failure
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Natriuretic effect of empagliflozin or placebo as an adjuvant to loop diuretic therapy
研究概览
简要总结
This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes. Participants will be randomized to empagliflozin or placebo for 6 weeks, followed by a crossover of placebo patients to active therapy at 6 weeks-12 weeks.
详细描述
This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes.
The broad study design aims to evaluate change in gold standard determined body fluid spaces, sodium avidity, and cardio-renal biomarkers longitudinally in patients treated with placebo vs. empagliflozin over a 6 week period. Primary analysis of the randomized intervention will occur during the 6 week double blind period. Crossover of placebo patients to active therapy from 6-12 weeks will provide additional exploratory mechanistic data at low incremental cost and provide added benefit to enrollment of the study.
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)
盲法说明
Double-blind
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
- •A clinical diagnosis of worsening heart failure (worsening of congestive symptoms with current therapies) in the opinion of the investigator.
- •A planned outpatient diuretic intervention (either up-titration of loop or addition of thiazide diuretic) for worsening heart failure per treating clinician. Diuretic intervention can occur via an unplanned in person visit (e.g., outpatient ambulatory clinic, emergency department, same day access visit) or via a telephone encounter (e.g., patient calling the clinic with reported weight gain and SOB that is prescribed uptitration of diuretic therapy).
- •Estimated or reported weight gain of at least 5 lbs.
- •Chronic daily oral loop diuretic dose ≥ 20mg furosemide equivalents for at least one month prior to enrollment
- •Estimated GFR (eGFR) ≥ 20 mL/min/1.73 m2
- •Age ≥ 18 years old
- •Signed informed consent
- •English speaking participants only
排除标准
- •Need for heart failure hospitalization at the time of randomization
- •Current use or plan to initiate renal replacement therapy
- •Significant bladder dysfunction or urinary incontinence
- •Inability to comply with the serial urine collection procedures
- •Chronic use of natriuretic doses of thiazide diuretics (≥50mg hydrochlorothiazide or equivalent)
- •Critical stenotic valvular disease, complex congenital heart disease or prior heart transplant
- •History of type 1 diabetes, diabetic ketoacidosis, "brittle" diabetes or frequent hypoglycemia or severe hypoglycemic episodes requiring emergent intervention (ER visit or EMS response, glucagon administration or forced oral carbs) in the last 6 months
- •History of or current urosepsis or frequent urinary tract infections
- •Anemia with hemoglobin <8g/dL (due to required phlebotomy for the study) or active bleeding
- •Pregnancy or breastfeeding
- •Appears unlikely or unable to participate in the required study procedures, as assessed by the study PI, study coordinator, or designee (ex: clinically-significant psychiatric, addictive, or neurological disease)
研究组 & 干预措施
Placebo, Then Empagliflozin
Participants first receive matching placebo daily for weeks 1-6, then will receive Empagliflozin 10 mg daily for weeks 7-12
干预措施: Placebo (Drug)
Placebo, Then Empagliflozin
Participants first receive matching placebo daily for weeks 1-6, then will receive Empagliflozin 10 mg daily for weeks 7-12
干预措施: Empagliflozin 10 mg (Drug)
Empagliflozin
Empagliflozin 10 mg daily for weeks 1-6
干预措施: Empagliflozin 10 mg (Drug)
结局指标
主要结局
Natriuretic effect of empagliflozin or placebo as an adjuvant to loop diuretic therapy
时间窗: Day 1
The natriuretic effect (urine sodium concentration) of each arm with loop diuretic therapy will be measured by the mmols of sodium excreted on day 1.
Change in plasma volume from baseline to 7 days
时间窗: Day 1 and Day 7
Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in plasma volume \[ml\] from Day 1 to Day 7, using I-131 albumin
Change in total body water from baseline to 7 days
时间窗: Day 1 and Day 7
Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in total body water \[liters\] from Day 1 to Day 7, using heavy water \[D2O)
次要结局
- Change in Chronic effects of empagliflozin on change in total body water during the open label extension.(Day 1 up to Day 84)
- Change in Chronic effects of empagliflozin vs placebo on plasma volume(Day 1 and day 42)
- Change in Chronic effects of empagliflozin on change in plasma volume during the open label extension.(Day 1 up to Day 84)
- Change in Chronic effects of empagliflozin vs placebo on change in total body water(Day 1 and day 42)