The Targeting Acute Congestion With Tolvaptan In Congestive Heart Failure Study
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 257
- Locations
- 18
- Primary Endpoint
- Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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)
Intervention: Tolvaptan (Drug)
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)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours
Time Frame: 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 Outcomes
- 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)
- Over-diuresis(72 hours)
- Worsening or Persistent Heart Failure or Death(72 hrs)
- Development of Worsening Renal Function(72 hours)
- Days Hospitalized or Deceased(30 days)
- All Cause Death or Rehospitalization(30 days)
- Hospital Stay(7 days)
- Dyspnea 11 Point NRS(0, 24, 48, and 72 hours)
- Freedom From Congestion(24, 48, and 72 hours)
- Serum Sodium(0, 24, 48, and 72 hours)