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

Condition(s) targeted: Congestive Heart Failure; Renal Insufficiency

Intervention: Hypertonic saline, then oral sodium chloride (Drug); Normal saline, then oral placebo capsule (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Barnes-Jewish Hospital Foundation

Official(s) and/or principal investigator(s):
Anitha Vijayan, M.D., Principal Investigator, Affiliation: Renal Division, Washington University School of Medicine
Kamalanathan K Sambandam, M.D., Principal Investigator, Affiliation: Renal Division, Washington University School of Medicine
Gregory A Ewald, M.D., Principal Investigator, Affiliation: Cardiovascular Division, Washington University School of Medicine

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

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

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

Primary outcome:

duration of hospitalization

weight loss at discharge

weight loss at 60 days

Secondary outcome:

number of readmissions

GFR by creatinine clearance at discharge

estimated GFR at 60 days after discharge

24hr urine output at discharge

need for inotrope or extracorporeal volume removal

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Adult patients (age ≥18) admitted with CHF exacerbation with NYHA Class III-IV

symptoms at screening.

- Left ventricular ejection fraction 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 /= 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.

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

Barnes-Jewish Hospital; Washington University School of Medicine, Saint Louis, Missouri 63110, United States; Recruiting
Anitha Vijayan, M.D., Principal Investigator
Kamalanathan K Sambandam, M.D., Sub-Investigator
Gregory A Ewald, M.D., Sub-Investigator

Related 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.

Starting date: November 2007
Ending date: July 2010
Last updated: January 27, 2009