Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure
- Registration Number
- NCT01644331
- Lead Sponsor
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 257
-
≥ 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
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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) Tolvaptan 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)
- Primary Outcome Measures
Name Time Method Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours 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
Name Time Method Renal Function 0, 24, 48 and 72 hours Change in Serum creatinine from baseline to 24, 48 and 72 hours
Weight Loss 0, 24, 48, and 72 hours Change in body weight from baseline to 24, 48, and 72 hours
Fluid Loss 0, 24, 48, and 72 hours Change from baseline fluid balance at 24, 48, and 72 hours
Dyspnea Likert 48 and 72 hours Number of patients that experience moderate or greater improvement (patient reported) in dyspnea by 7 point Likert scale at 48 and 72 hours
Over-diuresis 72 hours clinical evidence of volume depletion requiring intervention other than holding diuretics during the 72 hours after randomization
Worsening or Persistent Heart Failure or Death 72 hrs Number of patients with worsening heart failure or death
Development of Worsening Renal Function 72 hours increase in serum creatinine ≥ 0.3mg/dl from randomization at any time point during 72 hours after randomization
Days Hospitalized or Deceased 30 days Total days hospitalized or deceased during the 30 days after randomization
All Cause Death or Rehospitalization 30 days All cause death or rehospitalization (to include unscheduled clinic visits or ED visits) at 30 days (Kaplan-Meier and 95% confidence interval)
Hospital Stay 7 days Total days spent in hospital from baseline until discharge or death
Dyspnea 11 Point NRS 0, 24, 48, and 72 hours 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 24, 48, and 72 hours Jugular Venous Pressure (JVP) \< 8 cm, no orthopnea, trace peripheral edema or less, and will be assessed at 24, 48, and 72 hours
Serum Sodium 0, 24, 48, and 72 hours Change in serum sodium from baseline to 24, 48, and 72 hours
Trial Locations
- Locations (18)
Northeast Georgia Heart Center
🇺🇸Gainesville, Georgia, United States
University of Colorado at Denver and Health Sciences Center
🇺🇸Aurora, Colorado, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, 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
Allegheny Valley Hospital
🇺🇸Natrona Heights, Pennsylvania, United States
The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, 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
Mercer University School of Medicine
🇺🇸Macon, Georgia, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States