Clinical trial NCT00575484: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Congestive Heart Failure
Renal Insufficiency
Keywords: Congestive Heart Failure
Renal Insufficiency
Hypertonic Saline Solution
Diuretic Resistance
Cardiorenal Syndrome
Lead sponsor: Barnes-Jewish Hospital
Sponsor class: OTHER
Collaborators: name: Washington University School of Medicine
First posted: 2007-12-18
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: duration of hospitalization
timeFrame: duration of hospitalization
measure: weight loss at discharge
timeFrame: duration of hospitalization
measure: weight loss at 60 days
timeFrame: 60 days after discharge
Secondary outcomes:
measure: number of readmissions
timeFrame: 60 days after discharge
measure: GFR by creatinine clearance at discharge
timeFrame: duration of hospitalization
measure: estimated GFR at 60 days after discharge
timeFrame: 60 days after discharge
measure: 24hr urine output at discharge
timeFrame: last 24hrs of hospitalization
measure: need for inotrope or extracorporeal volume removal
timeFrame: 60 days after discharge
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital; Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Renal Division, Washington University School of Medicine
name: Anitha Vijayan, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Renal Division, Washington University School of Medicine
name: Kamalanathan K Sambandam, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Cardiovascular Division, Washington University School of Medicine
name: Gregory A Ewald, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.