Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure (TACTICS-HF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Duke University
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01644331
First received: July 17, 2012
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to see if taking tolvaptan by mouth in addition to the regular treatment received for shortness of breath due to heart failure will work better than the regular treatment alone. The study will also look to see if other symptoms of heart failure or problems associated with heart failure treatments, like changes in kidney function, are affected by tolvaptan.

The primary hypothesis is that the addition of oral Tolvaptan to fixed dose furosemide will be more effective at relieving dyspnea than fixed dose furosemide alone.


Condition Intervention Phase
Heart Failure
Dyspnea
Drug: Tolvaptan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Targeting Acute Congestion With Tolvaptan In Congestive Heart Failure Study

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Dyspnea improvement measured by Likert scale at 8 and 24 hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The proportion of patients with at least moderate improvement in dyspnea by Likert scale at both 8 AND 24 hours AND without the need for escalation of therapy due to worsening heart failure (rescue therapy) or death within 24 hours.


Secondary Outcome Measures:
  • Renal function [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Change from baseline blood urea nitrogen (BUN) at Day 7 or discharge Change from baseline serum creatinine at Day 7 or discharge

  • Body weight [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Change from baseline body weight at Day 7 or discharge

  • Fluid Loss [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Change from baseline fluid balance at Day 7 or discharge Change from baseline serum sodium at Day 7 or discharge

  • Breathing [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
    Change from baseline dyspnea at 72 hours

  • Hospital stay [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Total days spent in hospital from baseline until discharge or death

  • worsening heart failure [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Change from baseline heart failure assessment at Day 7 or discharge


Estimated Enrollment: 250
Study Start Date: October 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tolvaptan
IV furosemide (1 x oral dose given IV in Q12 hours divided doses or 40 mg IV Q12 hours, whichever is greater) plus oral Tolvaptan (given at 0, 12, 24 and 48 hours)
Drug: Tolvaptan
Tolvaptan (given at 0, 12, 24 and 48 hours)
Other Name: Samsca
Placebo Comparator: Placebo
IV furosemide (1 x oral dose given IV Q12 divided doses or 40mg IV Q12 hours, whichever is greater) plus oral placebo (given at O, 24, 48 hours)
Drug: Placebo
IV furosemide (1 x oral dose given IV in Q12 hours divided doses) plus oral placebo (given at 0, 12, 24 and 48 hours)
Other Name: Placebo

Detailed Description:

This study will be a randomized, double blind, placebo controlled, multi-center clinical trial of patients with signs and symptoms consistent with acute heart failure (AHF) within 24 hours of presentation at Emergency Department. A total of approximately 250 patients will be enrolled in the trial.

Patients will be randomized in a 1:1 ratio to either of 2 treatment regimens:

  • Fixed-dose IV furosemide (1 x total daily oral dose) given intravenously in divided doses every 12 hours or 40 mg IV Q12 hours, whichever is greater + oral Tolvaptan (given at 0, 12, 24 and 48 hours)
  • Fixed-dose IV furosemide (1 x total daily oral dose) given intravenously in divided doses every 12 hours or 40 mg IV Q12 hours, whichever is greater + oral placebo (given at 0, 12, 24 and 48 hours)

The study treatment regimen will be administered from randomization through 48 hours, at which point Tolvaptan/placebo will be discontinued and all diuretic treatment will be adjusted at the treating physician's discretion.

The primary endpoint will be the proportion of patients with at least moderate improvement in dyspnea by Likert scale at both 8 AND 24 hours AND without the need for escalation of therapy due to worsening heart failure (rescue therapy) or death within 24 hours.

Patients will be followed daily for the duration of hospitalization or for 7 days (whichever is shortest).

All patients will have Day 30 follow up phone contact for assessment of vital status and interval hospitalizations.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 18 years of age
  • Daily oral dose of furosemide between ≥ 40 mg(or equivalent)
  • Identified within 24 hours of presentation, defined for purposes of this study as the time of initial dose of intravenous loop diuretic
  • Prior clinical HF diagnosis that was treated with oral loop diuretics for at least 1 month
  • Admission for acute decompensated Heart Failure (HF) as determined by

    • dyspnea at rest or with minimal exertion
    • Brain Natriuretic Peptide (BNP) > 400 or NTproBNP > 2000 pg/mL

AND at least one of the following additional signs and symptoms:

  • Orthopnea
  • Peripheral edema
  • Elevated JVP (Jugular Venous Pressure)
  • Pulmonary rales
  • Congestion on Chest X-ray
  • No plan for revascularization, cardiac transplant, of ventricular assist device implantation, or other cardiac surgery within 60 days of randomization
  • Signed informed consent

Exclusion Criteria:

  • Serum Na > 140 meq/L
  • Received IV vasoactive treatment or ultra-filtration therapy for HF since initial presentation
  • Treatment plan during current hospitalization includes IV vasoactive treatment or ultra-filtration for HF
  • Systolic Blood Pressure (SBP)<90mmHg
  • Serum-Cr>3.5mg/dl or currently undergoing renal replacement therapy

    . Known underlying liver disease

  • Hemodynamically significant arrhythmias
  • ACS(Acute coronary syndrome) within 4 weeks prior to study entry
  • Active myocarditis
  • Hypertrophic obstructive, restrictive, constrictive cardiomyopathy
  • Severe stenotic valvular disease
  • Complex congenital heart disease
  • Constrictive pericarditis
  • Clinical evidence of digoxin toxicity
  • Need for mechanical hemodynamic support
  • Terminal illness (other than heart failure) with expected survival time of less than 1 year
  • History of adverse reaction to Tolvaptan
  • Enrollment or planned enrollment in another randomized clinical trial during this hospitalization
  • Pregnant or breast-feeding
  • Inability to comply with planned study procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01644331

Contacts
Contact: Michael Felker, MD 919-668-8919 michael.felker@dm.duke.edu
Contact: Pamela L Monds 919-668-8695 pamela.monds@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27713
Contact: Michael Felker, MD    919-668-8919    michael.felker@dm.duke.edu   
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Michael Felker, MD Duke Clinical Research Institute
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01644331     History of Changes
Other Study ID Numbers: Pro00037557
Study First Received: July 17, 2012
Last Updated: April 22, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on October 23, 2014