The Targeting Acute Congestion With Tolvaptan In Congestive Heart Failure Study

Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure

Sponsors

Lead sponsor: Duke University

Source Duke University
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.

Overall Status Completed
Start Date October 2012
Completion Date February 2016
Primary Completion Date February 2016
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours 8 and 24 hours
Secondary Outcome
Measure Time Frame
Renal Function 0, 24, 48 and 72 hours
Weight Loss 0, 24, 48, and 72 hours
Fluid Loss 0, 24, 48, and 72 hours
Dyspnea Likert 48 and 72 hours
Hospital Stay 7 days
Worsening or Persistent Heart Failure or Death 72 hrs
Over-diuresis 72 hours
Serum Sodium 0, 24, 48, and 72 hours
Dyspnea 11 Point NRS 0, 24, 48, and 72 hours
Freedom From Congestion 24, 48, and 72 hours
Development of Worsening Renal Function 72 hours
Days Hospitalized or Deceased 30 days
All Cause Death or Rehospitalization 30 days
Enrollment 257
Condition
Intervention

Intervention type: Drug

Intervention name: Tolvaptan

Description: IV furosemide plusTolvaptan (given at 0, 24 and 48 hours)

Arm group label: Tolvaptan

Other name: Samsca

Intervention type: Drug

Intervention name: Placebo

Description: IV furosemide plus oral placebo (given at 0, 24 and 48 hours)

Arm group label: Placebo

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Michael Felker, MD Principal Investigator Duke Clinical Research Institute
Location
facility
University of Colorado at Denver and Health Sciences Center | Aurora, Colorado, 80045, United States
Emory University School of Medicine | Atlanta, Georgia, 30322, United States
Northeast Georgia Heart Center | Gainesville, Georgia, 30501, United States
Mercer University School of Medicine | Macon, Georgia, 31201, United States
University of Chicago | Chicago, Illinois, 60637, United States
Indiana University School of Medicine | Indianapolis, Indiana, 46202, United States
Hennepin County Medical Center | Minneapolis, Minnesota, 55415, United States
Montefiore Medical Center | Bronx, New York, 10461, United States
University of North Carolina at Chapel Hill | Chapel Hill, North Carolina, 27599, United States
Novant Health Heart and Vascular | Charlotte, North Carolina, 28204, United States
Duke University Medical Center | Durham, North Carolina, 27713, United States
Southeastern Regional Medical Center | Lumberton, North Carolina, 28358, United States
The Christ Hospital | Cincinnati, Ohio, 45219, United States
University of Cincinnati Medical Center | Cincinnati, Ohio, 45267, United States
Allegheny Valley Hospital | Natrona Heights, Pennsylvania, 15065, United States
Grand View - Lehigh Valley Health Services | Sellersville, Pennsylvania, 18960, United States
UT Southwestern Medical center | Dallas, Texas, 75390, United States
Inova Heart and Vascular Institute | Falls Church, Virginia, 22042, United States
Location Countries

United States

Verification Date

March 2017

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Tolvaptan

Arm group type: Experimental

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 group label: Placebo

Arm group type: Placebo Comparator

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)

Acronym TACTICS-HF
Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov