Tolvaptan/Ultrafiltration in the Treatment of Acute Heart Failure (TUF)

January 27, 2016 updated by: Dr. Eugene Chung, The Christ Hospital

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45011
        • The Christ Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: usual care
IV loop diuretics
Drug: loop diuretic
ACTIVE_COMPARATOR: Usual care plus tolvaptan
IV loop diuretic plus Tolvaptan 30 mg orally once daily
Drug: tolvaptan
Drug: loop diuretic
ACTIVE_COMPARATOR: ultrafiltration
Volume removal through a brachial line extended length catheter or a quad lumen catheter via the internal jugular vein
Procedure: ultrafiltration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Net change in weight
Time Frame: day 1,2,3,4,5
day 1,2,3,4,5

Secondary Outcome Measures

Outcome Measure
Time Frame
net volume loss
Time Frame: day 1,2,3,4,5
day 1,2,3,4,5
urinary NGAL
Time Frame: Day 1,2,3,4,5
Day 1,2,3,4,5
dyspnea score
Time Frame: baseline and day 5
baseline and day 5
BNP change from admission to discharge
Time Frame: baseline and day 5
baseline and day 5
serum creatinine change
Time Frame: Day 1,2,3,4,5
Day 1,2,3,4,5
serum sodium and potassium changes
Time Frame: baseline through day 5
baseline through day 5
Quality of Life
Time Frame: day 4 of hospital stay
day 4 of hospital stay
all cause readmission
Time Frame: 30 day
30 day
all cause death
Time Frame: 30 day
30 day

Other Outcome Measures

Outcome Measure
Time Frame
nursing intensity
Time Frame: day 1,2,3,4,5
day 1,2,3,4,5
peripheral vs. central access, number of filters used, complications of heparin use
Time Frame: day 1,2,3,4,5
day 1,2,3,4,5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Christ Hospital

Investigators

  • Principal Investigator: Eugene S Chung, MD, The Christ Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2013

Primary Completion (ACTUAL)

December 1, 2015

Study Completion (ACTUAL)

December 1, 2015

Study Registration Dates

First Submitted

May 20, 2013

First Submitted That Met QC Criteria

May 28, 2013

First Posted (ESTIMATE)

May 29, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

January 28, 2016

Last Update Submitted That Met QC Criteria

January 27, 2016

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TUF-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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