Concentrated Saline Infusions and Increased Dietary Sodium With Diuretics for Heart Failure With Kidney Dysfunction - Full Text View

Sponsors and Collaborators:	Barnes-Jewish Hospital Foundation National Kidney Foundation
Information provided by:	Barnes-Jewish Hospital Foundation
ClinicalTrials.gov Identifier:	NCT00575484

Purpose

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.

Condition	Intervention	Phase
Congestive Heart Failure Renal Insufficiency	Drug: Hypertonic saline, then oral sodium chloride Drug: Normal saline, then oral placebo capsule	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study
Official Title:	Hypertonic Saline With Furosemide and a Normosodic Diet for the Treatment of Decompensated Congestive Heart Failure With Prerenal Physiology

Resource links provided by NLM:

MedlinePlus related topics: Dietary Sodium Diets Drinking Water Heart Failure Weight Control

Drug Information available for: Furosemide Chlorides Sodium chloride

U.S. FDA Resources

Further study details as provided by Barnes-Jewish Hospital Foundation:

Primary Outcome Measures:

duration of hospitalization [ Time Frame: duration of hospitalization ] [ Designated as safety issue: No ]
weight loss at discharge [ Time Frame: duration of hospitalization ] [ Designated as safety issue: No ]
weight loss at 60 days [ Time Frame: 60 days after discharge ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

number of readmissions [ Time Frame: 60 days after discharge ] [ Designated as safety issue: No ]
GFR by creatinine clearance at discharge [ Time Frame: duration of hospitalization ] [ Designated as safety issue: No ]
estimated GFR at 60 days after discharge [ Time Frame: 60 days after discharge ] [ Designated as safety issue: No ]
24hr urine output at discharge [ Time Frame: last 24hrs of hospitalization ] [ Designated as safety issue: No ]
need for inotrope or extracorporeal volume removal [ Time Frame: 60 days after discharge ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	November 2007
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator	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.
2: Active Comparator	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.

Arms

Assigned Interventions

1: Placebo Comparator

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.

2: Active Comparator

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00575484

Locations

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

Sponsors and Collaborators

Barnes-Jewish Hospital Foundation

National Kidney Foundation

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

More Information

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.

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.

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.

Responsible Party:	Washington University School of Medicine ( Anitha Vijayan, Associate Professor of Medicine )
Study ID Numbers:	00904-0407-01
Study First Received:	December 17, 2007
Last Updated:	September 2, 2009
ClinicalTrials.gov Identifier:	NCT00575484 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Barnes-Jewish Hospital Foundation:

Congestive Heart Failure
Renal Insufficiency
Hypertonic Saline Solution
Diuretic Resistance
Cardiorenal Syndrome

Study placed in the following topic categories:

Heart Failure
Renal Insufficiency
Heart Diseases
Urologic Diseases

Diuretics
Kidney Diseases
Furosemide

Additional relevant MeSH terms:

Renal Insufficiency
Heart Failure
Heart Diseases
Urologic Diseases
Natriuretic Agents

Physiological Effects of Drugs
Diuretics
Cardiovascular Diseases
Kidney Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2009