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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Study Primary Completion Date: July 2010

Intervention(s) in this Clinical Trial

• Drug: Hypertonic saline, then oral sodium chloride
  • 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.
• Drug: Normal saline, then oral placebo capsule
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
• Active Comparator: 2

Primary Measures

• duration of hospitalization
  • Time Frame: duration of hospitalization
    Safety Issue?: No
• weight loss at discharge
  • Time Frame: duration of hospitalization
    Safety Issue?: No
• weight loss at 60 days
  • Time Frame: 60 days after discharge
    Safety Issue?: No

Secondary Measures

• number of readmissions
  • Time Frame: 60 days after discharge
    Safety Issue?: No
• GFR by creatinine clearance at discharge
  • Time Frame: duration of hospitalization
    Safety Issue?: No
• estimated GFR at 60 days after discharge
  • Time Frame: 60 days after discharge
    Safety Issue?: No
• 24hr urine output at discharge
  • Time Frame: last 24hrs of hospitalization
    Safety Issue?: No
• need for inotrope or extracorporeal volume removal
  • Time Frame: 60 days after discharge
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Barnes-Jewish Hospital Foundation

Overall Clinical Trial Officials and Contacts

Anitha Vijayan, M.D. Principal Investigator Renal Division, Washington University School of Medicine  

Overall Contact: Anitha Vijayan, M.D. 314-362-7211 avijayan@im.wustl.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00575484

Study ID Number: 00904-0407-01

ClinicalTrials.gov Identifier: NCT00575484

Health Authority: United States: Institutional Review Board