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Phase 3 N=257 Randomized Double-blind Treatment

Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure

Heart Failure · Dyspnea

Enrolled (actual)
257
Serious AEs
3.9%
Results posted
Apr 2017
Primary outcome: Primary: Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours — 20; 26 Participants — p=0.315

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Tolvaptan (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Duke University
Primary completion
Feb 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours
20; 26 0.315
SECONDARY
Renal Function
0.13; 0.04; 0.10; 0.05; 0.03; 0.06 0.021 sig
SECONDARY
Weight Loss
-4.41; -1.16; -6.11; -3.46; -8.19; -5.53 0.430
SECONDARY
Fluid Loss
-2182.25; -1541.48; -1948.01; -1419.09; -1757.09; -1401.24 0.157
SECONDARY
Dyspnea Likert
88; 74; 69; 48 0.206
SECONDARY
Hospital Stay
6.46; 7.35 0.334
SECONDARY
Worsening or Persistent Heart Failure or Death
54; 60 0.148
SECONDARY
Over-diuresis
7; 3 0.334
SECONDARY
Serum Sodium
3.18; 0.23; 3.34; -0.24; 2.84; -0.44 0.241
SECONDARY
Dyspnea 11 Point NRS
-2.20; -1.84; -2.85; -2.29; -3.07; -2.42 0.303
SECONDARY
Freedom From Congestion
9; 12; 24; 20; 27; 17 0.471
SECONDARY
Development of Worsening Renal Function
50; 34 0.037 sig
SECONDARY
Days Hospitalized or Deceased
10.19; 11.69 0.373
SECONDARY
All Cause Death or Rehospitalization
0.33; 0.29 0.709

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

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) 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01644331). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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