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

Primary Purpose

Heart Failure, Dyspnea

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Tolvaptan
Placebo
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Colorado at Denver and Health Sciences Center
  • Emory University School of Medicine
  • Northeast Georgia Heart Center
  • Mercer University School of Medicine
  • University of Chicago
  • Indiana University School of Medicine
  • Hennepin County Medical Center
  • Montefiore Medical Center
  • University of North Carolina at Chapel Hill
  • Novant Health Heart and Vascular
  • Duke University Medical Center
  • Southeastern Regional Medical Center
  • The Christ Hospital
  • University of Cincinnati Medical Center
  • Allegheny Valley Hospital
  • Grand View - Lehigh Valley Health Services
  • UT Southwestern Medical center
  • Inova Heart and Vascular Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tolvaptan

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours
The number of patients with at least moderate improvement (as reported by patient) in dyspnea 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
Change in Serum creatinine from baseline to 24, 48 and 72 hours
Weight Loss
Change in body weight from baseline to 24, 48, and 72 hours
Fluid Loss
Change from baseline fluid balance at 24, 48, and 72 hours
Dyspnea Likert
Number of patients that experience moderate or greater improvement (patient reported) in dyspnea by 7 point Likert scale at 48 and 72 hours
Hospital Stay
Total days spent in hospital from baseline until discharge or death
Worsening or Persistent Heart Failure or Death
Number of patients with worsening heart failure or death
Over-diuresis
clinical evidence of volume depletion requiring intervention other than holding diuretics during the 72 hours after randomization
Serum Sodium
Change in serum sodium from baseline to 24, 48, and 72 hours
Dyspnea 11 Point NRS
Change in NRS for assessment of dyspnea from baseline to 24, 48, and 72 hours (scale ranges from 0-No difficulty breathing to 10-Difficulty as bad as you can imagine)
Freedom From Congestion
Jugular Venous Pressure (JVP) < 8 cm, no orthopnea, trace peripheral edema or less, and will be assessed at 24, 48, and 72 hours
Development of Worsening Renal Function
increase in serum creatinine ≥ 0.3mg/dl from randomization at any time point during 72 hours after randomization
Days Hospitalized or Deceased
Total days hospitalized or deceased during the 30 days after randomization
All Cause Death or Rehospitalization
All cause death or rehospitalization (to include unscheduled clinic visits or ED visits) at 30 days (Kaplan-Meier and 95% confidence interval)

Full Information

First Posted
July 17, 2012
Last Updated
March 17, 2017
Sponsor
Duke University
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1. Study Identification

Unique Protocol Identification Number
NCT01644331
Brief Title
Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure
Acronym
TACTICS-HF
Official Title
The Targeting Acute Congestion With Tolvaptan In Congestive Heart Failure Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of this study is to compare the effects of oral Tolvaptan vs. placebo as an adjunct to fixed dose IV furosemide on dyspnea relief in patients with acute decompensated heart failure 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
Detailed Description
This study will be a randomized, double blind, placebo controlled, multi-center clinical trial of patients with signs and symptoms consistent with 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 Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral Tolvaptan (given at 0, 24 and 48 hours) Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral placebo (given at 0, 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Dyspnea

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
257 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tolvaptan
Arm Type
Experimental
Arm Description
Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral Tolvaptan (given at 0, 24 and 48 hours)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral placebo (given at 0, 24 and 48 hours)
Intervention Type
Drug
Intervention Name(s)
Tolvaptan
Other Intervention Name(s)
Samsca
Intervention Description
IV furosemide plusTolvaptan (given at 0, 24 and 48 hours)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
IV furosemide plus oral placebo (given at 0, 24 and 48 hours)
Primary Outcome Measure Information:
Title
Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours
Description
The number of patients with at least moderate improvement (as reported by patient) in dyspnea 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.
Time Frame
8 and 24 hours
Secondary Outcome Measure Information:
Title
Renal Function
Description
Change in Serum creatinine from baseline to 24, 48 and 72 hours
Time Frame
0, 24, 48 and 72 hours
Title
Weight Loss
Description
Change in body weight from baseline to 24, 48, and 72 hours
Time Frame
0, 24, 48, and 72 hours
Title
Fluid Loss
Description
Change from baseline fluid balance at 24, 48, and 72 hours
Time Frame
0, 24, 48, and 72 hours
Title
Dyspnea Likert
Description
Number of patients that experience moderate or greater improvement (patient reported) in dyspnea by 7 point Likert scale at 48 and 72 hours
Time Frame
48 and 72 hours
Title
Hospital Stay
Description
Total days spent in hospital from baseline until discharge or death
Time Frame
7 days
Title
Worsening or Persistent Heart Failure or Death
Description
Number of patients with worsening heart failure or death
Time Frame
72 hrs
Title
Over-diuresis
Description
clinical evidence of volume depletion requiring intervention other than holding diuretics during the 72 hours after randomization
Time Frame
72 hours
Title
Serum Sodium
Description
Change in serum sodium from baseline to 24, 48, and 72 hours
Time Frame
0, 24, 48, and 72 hours
Title
Dyspnea 11 Point NRS
Description
Change in NRS for assessment of dyspnea from baseline to 24, 48, and 72 hours (scale ranges from 0-No difficulty breathing to 10-Difficulty as bad as you can imagine)
Time Frame
0, 24, 48, and 72 hours
Title
Freedom From Congestion
Description
Jugular Venous Pressure (JVP) < 8 cm, no orthopnea, trace peripheral edema or less, and will be assessed at 24, 48, and 72 hours
Time Frame
24, 48, and 72 hours
Title
Development of Worsening Renal Function
Description
increase in serum creatinine ≥ 0.3mg/dl from randomization at any time point during 72 hours after randomization
Time Frame
72 hours
Title
Days Hospitalized or Deceased
Description
Total days hospitalized or deceased during the 30 days after randomization
Time Frame
30 days
Title
All Cause Death or Rehospitalization
Description
All cause death or rehospitalization (to include unscheduled clinic visits or ED visits) at 30 days (Kaplan-Meier and 95% confidence interval)
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Felker, MD
Organizational Affiliation
Duke Clinical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado at Denver and Health Sciences Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northeast Georgia Heart Center
City
Gainesville
State/Province
Georgia
ZIP/Postal Code
30501
Country
United States
Facility Name
Mercer University School of Medicine
City
Macon
State/Province
Georgia
ZIP/Postal Code
31201
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Hennepin County Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Novant Health Heart and Vascular
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27713
Country
United States
Facility Name
Southeastern Regional Medical Center
City
Lumberton
State/Province
North Carolina
ZIP/Postal Code
28358
Country
United States
Facility Name
The Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Allegheny Valley Hospital
City
Natrona Heights
State/Province
Pennsylvania
ZIP/Postal Code
15065
Country
United States
Facility Name
Grand View - Lehigh Valley Health Services
City
Sellersville
State/Province
Pennsylvania
ZIP/Postal Code
18960
Country
United States
Facility Name
UT Southwestern Medical center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Inova Heart and Vascular Institute
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Not yet decided.
Citations:
PubMed Identifier
27654854
Citation
Felker GM, Mentz RJ, Cole RT, Adams KF, Egnaczyk GF, Fiuzat M, Patel CB, Echols M, Khouri MG, Tauras JM, Gupta D, Monds P, Roberts R, O'Connor CM. Efficacy and Safety of Tolvaptan in Patients Hospitalized With Acute Heart Failure. J Am Coll Cardiol. 2017 Mar 21;69(11):1399-1406. doi: 10.1016/j.jacc.2016.09.004. Epub 2016 Sep 18.
Results Reference
derived

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Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure

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