everest: efficacy of vasopressin antagonism in heart failure: outcome study with tolvaptan

Conditions: Congestive Heart Failure

Summary: the purpose of this study is to compare the effectiveness of tolvaptan or placebo in adults with worsening congestive heart failure (chf).

study design: multicenter, randomized, double-blind, placebo-controlled

Eligibility criteria:
inclusion criteria: * 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. exclusion criteria * 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.

Keywords: chronic heart failure heart failure