EVEREST: Efficacy of Vasopressin Antagonism in hEart failuRE: Outcome Study With Tolvaptan
This study has been completed.
Information provided by:
Otsuka Pharmaceutical Development & Commercialization, Inc.
First received: October 20, 2003
Last updated: May 2, 2012
Last verified: May 2012
The purpose of this study is to compare the effectiveness of tolvaptan or placebo in adults with worsening congestive heart failure (CHF).
Congestive Heart Failure
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
||Protocol 156-03-236: Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long Term Efficacy and Safety of Oral Tolvaptan Tablets in Subjects Hospitalized With Worsening Congestive Heart Failure
| Estimated Enrollment:
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||July 2006 (Final data collection date for primary outcome measure)
Study Design: Multicenter, randomized, double-blind, placebo-controlled
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Age greater than or equal to 18 years.
- Current hospitalization for chronic congestive heart failure with admission up to 48 hours prior to randomization. Chronic heart failure is defined as requiring treatment for a minimum of 30 days prior to hospitalization.
The subject must have signs of extracellular volume expansion, defined as two or more of the following: a) jugular venous distention; b) pitting edema (>1+); or c) dyspnea.
- NYHA Class III or IV at the time of hospitalization.
- Left Ventricular Ejection Fraction < = 40% within one year.
- Women who will not adhere to the reproductive precautions as outlined in the Informed Consent form.
- Positive urine pregnancy test.
- Inability to provide written informed consent.
- Cardiac surgery within 60 days of potential study enrollment, excluding percutaneous coronary interventions.
- Planned revascularization procedures, electrophysiologic (EP) device implantation, cardiac mechanical support implantation, cardiac transplantation, or other cardiac surgery within 30 days following study enrollment.
- Subjects who are on cardiac mechanical support.
- History of bi-ventricular pacer placement within the last 60 days.
- Co-morbid condition with an expected survival less than six months.
- Subjects with acute ST segment elevation myocardial infarction at the time of hospitalization.
- History of sustained ventricular tachycardia or ventricular fibrillation within 30 days, unless in the presence of an automatic implantable cardioverter defibrillator.
- History of a cerebrovascular accident within the last 30 days.
- Hemodynamically significant uncorrected primary cardiac valvular disease.
- Hypertrophic cardiomyopathy (obstructive or non-obstructive).
- CHF due to uncorrected thyroid disease, active myocarditis or known amyloid cardiomyopathy.
- Subjects with progressive or episodic neurological disease such as multiple sclerosis or history of multiple strokes.
- History of primary significant liver disease or acute hepatic failure, as defined by the investigator.
- History of poorly controlled diabetes mellitus.
- Morbid obesity, defined as > 159 kg (or 350 lbs) or BMI > 40.
- Supine systolic arterial blood pressure < 90 mmHg.
- Serum creatinine > 3.5 mg/dL or > 309.4 mmol/L.
- Serum potassium > 5.5 mEq/L or > 5.5 mmol/L.
- Hemoglobin < 9 g/dL or < 90 g/L.
- History of hypersensitivity and/or idiosyncratic reaction to benzazepine derivatives (such as benazapril).
- History of drug or medication abuse within the past year, or current alcohol abuse.
- Inability to take oral medications.
- Participation in another clinical drug or device trial within the past 30 days.
- Previous participation in this or any other tolvaptan clinical trial.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00071331
Otsuka Pharmaceutical Development & Commercialization, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Mentz RJ, Greene SJ, Ambrosy AP, Vaduganathan M, Subacius HP, Swedberg K, Maggioni AP, Nodari S, Ponikowski P, Anker SD, Butler J, Gheorghiade M. Clinical profile and prognostic value of anemia at the time of admission and discharge among patients hospitalized for heart failure with reduced ejection fraction: findings from the EVEREST trial. Circ Heart Fail. 2014 May;7(3):401-8. doi: 10.1161/CIRCHEARTFAILURE.113.000840. Epub 2014 Apr 15.
Hauptman PJ, Burnett J, Gheorghiade M, Grinfeld L, Konstam MA, Kostic D, Krasa HB, Maggioni A, Ouyang J, Swedberg K, Zannad F, Zimmer C, Udelson JE; Everest Investigators. Clinical course of patients with hyponatremia and decompensated systolic heart failure and the effect of vasopressin receptor antagonism with tolvaptan. J Card Fail. 2013 Jun;19(6):390-7. doi: 10.1016/j.cardfail.2013.04.001. Epub 2013 May 14.
O'Connor CM, Miller AB, Blair JE, Konstam MA, Wedge P, Bahit MC, Carson P, Haass M, Hauptman PJ, Metra M, Oren RM, Patten R, Piña I, Roth S, Sackner-Bernstein JD, Traver B, Cook T, Gheorghiade M; Efficacy of Vasopressin Antagonism in heart Failure Outcome Study with Tolvaptan (EVEREST) investigators. Causes of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: results from Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) program. Am Heart J. 2010 May;159(5):841-849.e1. doi: 10.1016/j.ahj.2010.02.023. Erratum in: Am Heart J. 2012 May;163(5):900.
Blair JE, Zannad F, Konstam MA, Cook T, Traver B, Burnett JC Jr, Grinfeld L, Krasa H, Maggioni AP, Orlandi C, Swedberg K, Udelson JE, Zimmer C, Gheorghiade M; EVEREST Investigators. Continental differences in clinical characteristics, management, and outcomes in patients hospitalized with worsening heart failure results from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) program. J Am Coll Cardiol. 2008 Nov 11;52(20):1640-8. doi: 10.1016/j.jacc.2008.07.056.
Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C; Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007 Mar 28;297(12):1332-43. Epub 2007 Mar 25.
Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C; Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007 Mar 28;297(12):1319-31. Epub 2007 Mar 25.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 20, 2003
||May 2, 2012
||United States: Food and Drug Administration
Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
chronic heart failure
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 23, 2016
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs