Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure

NCT ID: NCT01644331

Last Updated: 2017-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 257 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-02-29

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.

Conditions

Heart Failure; Dyspnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tolvaptan

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)

Group Type: EXPERIMENTAL

Tolvaptan

Intervention Type: DRUG

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

Placebo

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Tolvaptan

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Samsca

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Felker, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

Locations

University of Colorado at Denver and Health Sciences Center

Aurora, Colorado, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Northeast Georgia Heart Center

Gainesville, Georgia, United States

Mercer University School of Medicine

Macon, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Indiana University School of Medicine

Indianapolis, Indiana, United States

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Montefiore Medical Center

The Bronx, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Novant Health Heart and Vascular

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Southeastern Regional Medical Center

Lumberton, North Carolina, United States

The Christ Hospital

Cincinnati, Ohio, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Allegheny Valley Hospital

Natrona Heights, Pennsylvania, United States

Grand View - Lehigh Valley Health Services

Sellersville, Pennsylvania, United States

UT Southwestern Medical center

Dallas, Texas, United States

Inova Heart and Vascular Institute

Falls Church, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27654854 (View on PubMed)

Other Identifiers

Pro00037557

Identifier Type: -

Identifier Source: org_study_id