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

NCT00575484 | Terminated Phase 2 DMC

• 1 other identifier: 00904-0407-01
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Congestive Heart Failure; Renal Insufficiency

Keywords

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

Outcome Measures

Primary Outcomes (3)

• duration of hospitalization

  duration of hospitalization

• weight loss at discharge

  duration of hospitalization

• weight loss at 60 days

  60 days after discharge

Secondary Outcomes (5)

• 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

Study Arms (2)

1

PLACEBO COMPARATOR

Drug: Normal saline, then oral placebo capsule

2

ACTIVE COMPARATOR

Drug: Hypertonic saline, then oral sodium chloride

Interventions

Hypertonic saline, then oral sodium chloride DRUG

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.

2

Normal saline, then oral placebo capsule DRUG

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.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Barnes-Jewish Hospital: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Barnes-Jewish Hospital; Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• 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.

  PMID: 10915397 BACKGROUND

• 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.

  PMID: 10938493 BACKGROUND

• 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.

  PMID: 12660669 BACKGROUND

• 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.

  PMID: 15963399 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Renal Insufficiency; Cardio-Renal Syndrome

Interventions

Saline Solution, Hypertonic; Saline Solution

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 17, 2007
• First Posted: December 18, 2007
• Study Start: November 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: January 24, 2014

Record last verified: 2014-01

Locations

US (1)