NCT01644331

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
257

participants targeted

Target at P50-P75 for phase_3 heart-failure

Timeline
Completed

Started Oct 2012

Typical duration for phase_3 heart-failure

Geographic Reach
1 country

18 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 17, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 19, 2012

Completed
2 months until next milestone

Study Start

First participant enrolled

October 1, 2012

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

April 27, 2017

Completed
Last Updated

April 27, 2017

Status Verified

March 1, 2017

Enrollment Period

3.3 years

First QC Date

July 17, 2012

Results QC Date

January 6, 2017

Last Update Submit

March 17, 2017

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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.

    8 and 24 hours

Secondary Outcomes (13)

  • 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

  • +8 more secondary outcomes

Study Arms (2)

Tolvaptan

EXPERIMENTAL

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)

Drug: Tolvaptan

Placebo

PLACEBO COMPARATOR

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)

Drug: Placebo

Interventions

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

Also known as: Samsca
Tolvaptan

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

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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

You may not qualify if:

  • 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

University of Colorado at Denver and Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Northeast Georgia Heart Center

Gainesville, Georgia, 30501, United States

Location

Mercer University School of Medicine

Macon, Georgia, 31201, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Novant Health Heart and Vascular

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27713, United States

Location

Southeastern Regional Medical Center

Lumberton, North Carolina, 28358, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Allegheny Valley Hospital

Natrona Heights, Pennsylvania, 15065, United States

Location

Grand View - Lehigh Valley Health Services

Sellersville, Pennsylvania, 18960, United States

Location

UT Southwestern Medical center

Dallas, Texas, 75390, United States

Location

Inova Heart and Vascular Institute

Falls Church, Virginia, 22042, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Heart FailureDyspnea

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesRespiration DisordersRespiratory Tract DiseasesSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
G. Michael Felker, MD
Organization
Duke Clinical Research Institute

Study Officials

  • Michael Felker, MD

    Duke Clinical Research Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 17, 2012

First Posted

July 19, 2012

Study Start

October 1, 2012

Primary Completion

February 1, 2016

Study Completion

February 1, 2016

Last Updated

April 27, 2017

Results First Posted

April 27, 2017

Record last verified: 2017-03

Locations