Tolvaptan/Ultrafiltration in the Treatment of Acute Heart Failure

Acute Decompensated Heart Failure Clinical Trial

— TUF  

Official title:

Primary Mode of Therapy in Acute Decompensated Heart Failure:Comparison Between Usual Care Plus Tolvaptan and Ultrafiltration.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01863511
• Other study ID #: TUF-01
• Status: Completed
• Phase: Phase 4
• First received: May 20, 2013
• Last updated: January 27, 2016
• Start date: May 2013
• Est. completion date: December 2015

Study information

• Verified date: February 2015
• Source: The Christ Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

For patients hospitalized with acute decompensated heart failure,volume removal remains the primary therapeutic objective. The current standard of care remains loop diuretics.The high likelihood of readmissions and poor outcomes highlights the need to examine and improve in-hospital protocols for these patients. Ultrafiltration allows for greater volume removal, less neurohormonal stimulation and greater sodium removal.However it is associated with increased costs, line complications, and relative immobility during treatment. Tolvaptan in addition to diuretic therapy has been shown to improve the amount of volume removed compared to diuretic alone.

The study proposes to compare the strategy of adding tolvaptan to usual care with ultrafiltration as primary mode of therapy in acute decompensated HF(ADHF) patients.

Hypothesis: addition of tolvaptan to usual care for hospitalized HF patients will result in:

• greater volume and weight reduction compared with usual care

• similar efficacy outcomes compared with ultrafiltration, with less complications of therapy

Description:

Study design is a prospective randomized open labeled and unblinded comparison of two different approaches to volume removal. Enrolled patients will be evaluated for target weight to be removed. Patients will be randomized to usual care (UC), usual care plus tolvaptan (UC+T) or ultrafiltration (UF), within 12 hours of presentation.

Treatment in the UC and UC+T arms will begin with a furosemide bolus(double the home dose or if unavailable, 60mg) and continue with a drip(10 or 20 mg/hr). In addition the UC+T group will be treated with tolvaptan 30 mg orally once daily.

Patients in the UF arm will be treated with UF administered through a brachial line or a catheter in the internal jugular vein. Loop and thiazide diuretics will be discontinued, although aldosterole antagonists will be continued.

Urinary neutrophil gelatinase associated lipocalcin(uNGAL)levels are elevated in renal dysfunction and may be a sensitive biomarker to distinguish between intrinsic renal damage and reversible, transient prerenal azotemia.Characterizing the changes in uNGAL levels during the course of ADHF therapy, in comparison with patient weight, BUN and creatinine levels is an important step in establishing the role of this potential promising biomarker in ADHF treatment strategies.

Protocol highlights for all patients include:

Baseline labs and daily through day 4 and at discharge(BMP, BNP, CBC, urine creatinine and sodium, uNGAL)

• Daily am weights

• Daily volume status:total intake, urine output, ultrafiltrate volume

• Collect all urine and ultrafiltrate in a 24 hour collection bag, record volume, creatinine and Na levels

• length of stay

• hospital day 4: Minnesota Living with Heart Failure questionnaire

• Cost of hospitalization

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 2 of 3 physical exam findings of volume overload (rales, JVP over 5 cm and edema)

• BNP over 300

• no contraindication to ultrafiltration (line insertion, heparin use)

Exclusion Criteria:

• serum creatinine > 3mg/dL or Na > 145

• inotrope or vasopressor dependency

• active infection, including urinary tract

• resynchronization therapy or coronary intervention in past 30 days

• life expectancy less than 6 months

• hypertrophic obstructive cardiomyopathy with peak resting gradient > 20 mmHg

• IV contrast or NSAID use in the past 1 week (uNGAL related requirement)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Heart Failure

Intervention

Drug:
• loop diuretic

• tolvaptan

Procedure:
• ultrafiltration

Locations

Country	Name	City	State
United States	The Christ Hospital	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Christ Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	nursing intensity		day 1,2,3,4,5	No
Other	peripheral vs. central access, number of filters used, complications of heparin use		day 1,2,3,4,5	No
Primary	Net change in weight		day 1,2,3,4,5	No
Secondary	net volume loss		day 1,2,3,4,5	No
Secondary	urinary NGAL		Day 1,2,3,4,5	No
Secondary	dyspnea score		baseline and day 5	No
Secondary	BNP change from admission to discharge		baseline and day 5	No
Secondary	serum creatinine change		Day 1,2,3,4,5	No
Secondary	serum sodium and potassium changes		baseline through day 5	No
Secondary	Quality of Life		day 4 of hospital stay	No
Secondary	all cause readmission		30 day	No
Secondary	all cause death		30 day	No