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

Primary Purpose

Congestive Heart Failure, Renal Insufficiency

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Hypertonic saline, then oral sodium chloride

Normal saline, then oral placebo capsule

About this trial

This is an interventional treatment trial for Congestive Heart Failure focused on measuring Congestive Heart Failure, Renal Insufficiency, Hypertonic Saline Solution, Diuretic Resistance, Cardiorenal Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Barnes-Jewish Hospital; Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

duration of hospitalization

weight loss at discharge

weight loss at 60 days

Secondary Outcome Measures

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

Full Information

NCT ID

NCT00575484

First Posted

December 17, 2007

Last Updated

January 22, 2014

Sponsor

Barnes-Jewish Hospital

Collaborators

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT00575484

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2014

Overall Recruitment Status

Terminated

Study Start Date

November 2007 (undefined)

Primary Completion Date

July 2008 (Actual)

Study Completion Date

July 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Barnes-Jewish Hospital

Collaborators

Washington University School of Medicine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Congestive Heart Failure, Renal Insufficiency

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Placebo Comparator

Arm Title

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Hypertonic saline, then oral sodium chloride

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Normal saline, then oral placebo capsule

Intervention Description

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.

Primary Outcome Measure Information:

Title

duration of hospitalization

Time Frame

duration of hospitalization

Title

weight loss at discharge

Time Frame

duration of hospitalization

Title

weight loss at 60 days

Time Frame

60 days after discharge

Secondary Outcome Measure Information:

Title

number of readmissions

Time Frame

60 days after discharge

Title

GFR by creatinine clearance at discharge

Time Frame

duration of hospitalization

Title

estimated GFR at 60 days after discharge

Time Frame

60 days after discharge

Title

24hr urine output at discharge

Time Frame

last 24hrs of hospitalization

Title

need for inotrope or extracorporeal volume removal

Time Frame

60 days after discharge

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anitha Vijayan, M.D.

Organizational Affiliation

Renal Division, Washington University School of Medicine

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Kamalanathan K Sambandam, M.D.

Organizational Affiliation

Renal Division, Washington University School of Medicine

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gregory A Ewald, M.D.

Organizational Affiliation

Cardiovascular Division, Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Barnes-Jewish Hospital; Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

10915397

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.

Results Reference

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PubMed Identifier

10938493

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. doi: 10.1016/s1388-9842(00)00094-5.

Results Reference

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PubMed Identifier

12660669

Citation

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.

Results Reference

background

PubMed Identifier

15963399

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. doi: 10.1016/j.jacc.2005.01.059.

Results Reference

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

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