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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01644331
First received: July 17, 2012
Last updated: March 10, 2016
Last verified: March 2016
History of Changes
  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:

U.S. FDA Resources

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
Enrollment: 257
Study Start Date: October 2012
Study Completion Date: February 2016
Primary Completion Date: February 2016 (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)

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   (Adult, Senior)
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

Locations
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27713
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Michael Felker, MD Duke Clinical Research Institute
  More Information

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01644331     History of Changes
Other Study ID Numbers: Pro00037557 
Study First Received: July 17, 2012
Last Updated: March 10, 2016
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Undecided
Plan Description: Not yet decided.

Additional relevant MeSH terms:
Heart Failure
Dyspnea
Heart Diseases
Cardiovascular Diseases
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Furosemide
 Tolvaptan
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antidiuretic Hormone Receptor Antagonists

ClinicalTrials.gov processed this record on September 23, 2016