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

Congestive Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00575484
• Other study ID #: 00904-0407-01
• Status: Terminated
• Phase: Phase 2
• First received: December 17, 2007
• Last updated: January 22, 2014
• Start date: November 2007
• Est. completion date: July 2008

Study information

• Verified date: January 2014
• Source: Barnes-Jewish Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure
• Renal Insufficiency

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Barnes-Jewish Hospital; Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Barnes-Jewish Hospital	Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	duration of hospitalization		duration of hospitalization	No
Primary	weight loss at discharge		duration of hospitalization	No
Primary	weight loss at 60 days		60 days after discharge	No
Secondary	number of readmissions		60 days after discharge	No
Secondary	GFR by creatinine clearance at discharge		duration of hospitalization	No
Secondary	estimated GFR at 60 days after discharge		60 days after discharge	No
Secondary	24hr urine output at discharge		last 24hrs of hospitalization	No
Secondary	need for inotrope or extracorporeal volume removal		60 days after discharge	No