Concentrated Saline Infusions and Increased Dietary Sodium With Diuretics for Heart Failure With Kidney Dysfunction

Study Overview
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Brief Summary
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At present the standard management of fluid overload in patients with congestive heart failure (CHF) involves limiting the intake of salt and water while administering high dose diuretics, often at the cost of deteriorating kidney function. However, another group of researchers has previously shown that intravenously infusing small volumes of concentrated saline during diuretic dosing and liberalizing dietary salt intake while continuing to limit water consumption resulted in improved fluid removal in CHF patients. Furthermore, less deterioration in kidney function, shorter hospitalizations, reduced readmission rates, and even reduced mortality were observed. The present study will examine this novel therapy in a population of 60 patients with underlying severe CHF and kidney dysfunction hospitalized for the management of fluid overload. Half of these patients will receive investigational treatment with concentrated salt infusions and liberalized salt consumption during diuretic therapy. All patients will otherwise receive the standard therapies for heart failure, including restrictions on water consumption. This study will attempt to verify the improvements in clinical endpoints previously described and define the mechanisms of enhanced fluid removal.

Official Title
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Hypertonic Saline With Furosemide and a Normosodic Diet for the Treatment of Decompensated Congestive Heart Failure With Prerenal Physiology

Conditions
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Congestive Heart Failure, Renal Insufficiency

Intervention / Treatment
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* Drug: Hypertonic saline, then oral sodium chloride
* Drug: Normal saline, then oral placebo capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (age ≥18) admitted with CHF exacerbation with NYHA Class III-IV symptoms at screening. Left ventricular ejection fraction </= 45%, as determined by previous echocardiogram, left ventricular angiogram, or thallium myocardial imaging. Estimated GFR <60 ml/min/1.7m² with significant prerenal physiology as judged by prior documented volume mediated changes in renal function, a fractional excretion of urea <35%, or a fractional excretion of sodium <1%. For GFR 30-60: must have serum sodium </= 135 mEq/L OR large home diuretic dose (total daily loop diuretic dose >/= 120 mg/d in furosemide equivalents OR concomitant thiazide use). For GFR <30: no additional criteria needed. Exclusion Criteria: Admit estimated GFR < 15mL/min or predicted need for chronic hemodialysis within the next 60 days. Cause of acute kidney injury other than prerenal physiology. No loop diuretic prior to admission or loop diuretic initiated within the 2 wks prior to admission. Medicine or dietary noncompliance expected to prevent successful study participation. > 36hrs since presentation to screening. Serum Na > 145 mEq/L OR < 120 mEq/L at screening. Systolic blood pressure > 180 mmHg at screening. Presentation with acute coronary syndrome OR left heart catheterization planned at screening. Current or impending respiratory failure at screening. Current calcineurin inhibitor or nesiritide use. Nephrotic-range proteinuria. Clinical evidence for the presence of cirrhosis with bilirubin >/= 2mg/dL or international normalized ratio (not on coumadin) >/= 1.7. Presence of another active medical issue which may prolong hospital admission or delay aggressive CHF therapy. Participation in another interventional study. Pregnancy. Prisoners.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: Normal saline, then oral placebo capsule<br>* 20mL normal saline infusion X 30min BID dosed simultaneously with IV bolus furosemide BID (latter dose per treating physician) PLUS 2gm sodium diet PLUS 1.5L fluid restriction. After switch to oral diuretic, begin oral placebo capsule BID, dosed with loop diuretic (dose per treating physician) PLUS 2gm sodium diet PLUS 1.5L fluid restriction.<br>|
| Active Comparator: 2<br> | Drug: Hypertonic saline, then oral sodium chloride<br>* 2mL/kg hypertonic saline (4.4% NaCl if serum sodium </=135, else 2.8% NaCl) infused over 30min BID and dosed simultaneously with IV bolus furosemide BID (latter dose per treating physician) until patient is switched to oral loop diuretic. After switch to oral diuretic, subject will receive oral 0.75gm sodium (NaCL) capsule dosed BID with loop diuretic (latter dose per treating physician) until 60d after discharge.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of hospitalization |  | duration of hospitalization | 
| weight loss at discharge |  | duration of hospitalization | 
| weight loss at 60 days |  | 60 days after discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of readmissions |  | 60 days after discharge | 
| GFR by creatinine clearance at discharge |  | duration of hospitalization | 
| estimated GFR at 60 days after discharge |  | 60 days after discharge | 
| 24hr urine output at discharge |  | last 24hrs of hospitalization | 
| need for inotrope or extracorporeal volume removal |  | 60 days after discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Congestive Heart Failure, Renal Insufficiency, Hypertonic Saline Solution, Diuretic Resistance, Cardiorenal Syndrome