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

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 Overview

• Status: Terminated
• Conditions: Renal Insufficiency; Congestive Heart Failure
• Intervention / Treatment: Drug: Normal saline, then oral placebo capsule; Drug: Hypertonic saline, then oral sodium chloride

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital; Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 2	Drug: Hypertonic saline, then oral sodium chloride; 2mL/kg hypertonic saline (4.4% NaCl if serum sodium
PLACEBO_COMPARATOR: 1	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Barnes-Jewish Hospital
• Collaborators: Washington University School of Medicine
• Investigators: Principal Investigator: Anitha Vijayan, M.D., Renal Division, Washington University School of Medicine; Principal Investigator: Kamalanathan K Sambandam, M.D., Renal Division, Washington University School of Medicine; Principal Investigator: Gregory A Ewald, M.D., Cardiovascular Division, Washington University School of Medicine

Publications and helpful links

General Publications

• Paterna S, Parrinello G, Amato P, Dominguez L, Pinto A, Maniscalchi T, Cardinale A, Licata A, Amato V, Licata G, Di Pasquale P. Tolerability and efficacy of high-dose furosemide and small-volume hypertonic saline solution in refractory congestive heart failure. Adv Ther. 1999 Sep-Oct;16(5):219-28.
• Paterna S, Di Pasquale P, Parrinello G, Amato P, Cardinale A, Follone G, Giubilato A, Licata G. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure. Eur J Heart Fail. 2000 Sep;2(3):305-13. doi: 10.1016/s1388-9842(00)00094-5.
• Licata G, Di Pasquale P, Parrinello G, Cardinale A, Scandurra A, Follone G, Argano C, Tuttolomondo A, Paterna S. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Am Heart J. 2003 Mar;145(3):459-66. doi: 10.1067/mhj.2003.166.
• Paterna S, Di Pasquale P, Parrinello G, Fornaciari E, Di Gaudio F, Fasullo S, Giammanco M, Sarullo FM, Licata G. Changes in brain natriuretic peptide levels and bioelectrical impedance measurements after treatment with high-dose furosemide and hypertonic saline solution versus high-dose furosemide alone in refractory congestive heart failure: a double-blind study. J Am Coll Cardiol. 2005 Jun 21;45(12):1997-2003. doi: 10.1016/j.jacc.2005.01.059.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (ACTUAL): July 1, 2008
• Study Completion (ACTUAL): July 1, 2008

Study Registration Dates

• First Submitted: December 17, 2007
• First Submitted That Met QC Criteria: December 17, 2007
• First Posted (ESTIMATE): December 18, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): January 24, 2014
• Last Update Submitted That Met QC Criteria: January 22, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Renal Insufficiency; Cardiorenal Syndrome; Congestive Heart Failure; Hypertonic Saline Solution; Diuretic Resistance
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Heart Failure; Renal Insufficiency
• Other Study ID Numbers: 00904-0407-01