Mechanism and Effects of Manipulating Chloride Homeostasis in Acute Heart Failure
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in Blood Volume
研究概览
简要总结
The purpose of this study is to understand the effects of chloride supplementation on volume-overloaded acute heart failure patients concomitantly treated with IV diuretics.
详细描述
The overarching goal of this proposal is to develop a comprehensive understanding of the biology and therapeutic potential of sodium-free chloride supplementation. While sodium homeostasis has been the focus of substantial investigation, very little research has been devoted to understanding chloride homeostasis. Thus, this proposal is designed to obtain the full spectrum of information pertaining to chloride, such as novel areas with great interest by the scientific community (i.e. modulation of the WNK-kinase system and the use of exosomes), to more practical/basic questions (i.e. what happens to sodium chloride balance when a patient is challenged with chloride). The proposed outpatient study has been designed to serve as a real world efficacy study. With extensive biobanking and analysis of samples in the proposed setting, there is the potential to be able to deliver a great wealth of information on the biology and therapeutic potential of manipulating chloride homeostasis in heart failure.
Research confirms that many heart failure therapies demonstrate measurable benefit in highly controlled environments, but lack effectiveness when studied in decompensated patients receiving standard decongestive therapies. As such, this study seeks to understand the effects of chloride supplementation on volume-overloaded patients concomitantly treated with IV diuretics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, 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
- •Clinical diagnosis of decompensated heart failure with at least one objective sign of volume overload (rales, edema, elevated jugular venous pressure (JVP), or weight gain of at least 5 pounds)
- •A projected need by the treating clinician for continued treatment with IV diuretics
- •Chronic loop diuretic use
排除标准
- •Inability to commit to or comply with serial visits for treatment in the Yale Transitional Care Center (YTCC)
- •History of severe metabolic or respiratory acidosis within 30 days of enrollment
- •Use of metformin, acetazolamide, or any other agent that could predispose to acidosis. Patients who are on metformin may be enrolled if their metformin can be discontinued safely for the duration of the study. Any participants who have consistently elevated Blood glucose readings > 200 mg/dL while inpatient will not be enrolled.
- •Serum bicarbonate level <20mmol/L
- •Estimated glomerular filtration rate <20 mL/min or renal replacement therapy
- •Appears unlikely, or unable to participate in the required study procedures, as assessed by the study PI or research registered nurse (RN) (ex: clinically-significant psychiatric, addictive, or neurological disease)
- •Inability to give written informed consent or follow study protocol
研究组 & 干预措施
Placebo
Participants will be randomized to 7 days of therapy with either 115 mmol/day of lysine chloride or placebo. People in the Placebo group will receive placebo.
干预措施: Placebo (Other)
Lysine Chloride
Participants will be randomized to 7 days of therapy with either 115 mmol/day of lysine chloride or placebo. People in the Lysine Chloride group will receive the active intervention.
干预措施: Lysine Chloride (Drug)
结局指标
主要结局
Change in Blood Volume
时间窗: Daily for 7 days
Volumex is albumin labeled with the iodine isotope I-131 and is an FDA-approved method used to determine total blood volume. A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of blood collection will be compared across the 7 day collection period between intervention and placebo arms.
次要结局
- Change in Cystatin C(Daily for 7-days)
- Change in Bicarbonate(Daily for 7-days)
- Change in Chloride(Daily for 7-days)
- Change in Log NTpro-BNP(Daily for 7-days)
- Change in Serum Creatinine(Daily for 7-days)