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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00071331
• Date of registration: 20/10/2003
• Primary sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Public title: EVEREST: Efficacy of Vasopressin Antagonism in hEart failuRE: Outcome Study With Tolvaptan
• Scientific title: 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
• Date of first enrolment: September 2003
• Target sample size: 3600
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00071331
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Countries of recruitment

Argentina, Belgium, Brazil, Canada, Czech Republic, France, Germany, Italy, Netherlands, Norway, Poland, Romania, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Congestive Heart Failure

Intervention(s)

Drug: Tolvaptan

Secondary ID(s)

156-03-236

Source(s) of Monetary Support

Please refer to primary and secondary sponsors