EVEREST: Efficacy of Vasopressin Antagonism in hEart failuRE: Outcome Study With Tolvaptan

• Status: Completed
• Trial end date: 2006-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Treatments: Tolvaptan

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.