Safety and Efficacy of Conivaptan in Hyponatremic Patients With Symptomatic Acute Decompensated Heart Failure (ADHF)
Condition: Hyponatremia; Acute Decompensated Heart Failure
MeSH terms: Heart Failure; Hyponatremia
Intervention: conivaptan; placebo
Intervention description: Premix bag; Premix bag
Intervention MeSH terms: Conivaptan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hyponatremia; euvolemic hyponatremia; hypervolemic hyponatremia; acute decompensated heart failure; conivaptan; Vaprisol

Summary:

      This study will evaluate the safety and effectiveness of Conivaptan, a vasopressin
      antagonist, in the treatment of hyponatremic subjects having symptomatic acute decompensated
      heart failure (ADHF).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Presents to emergency department with documented history of CHF and symptomatic ADHF,
             will be treated for ADHF, and primary reason for admission to the hospital is ADHF

          -  Dyspnea at rest or with minimal exertion and must have moderate shortness of breath
             (SOB) in any of the first three Provocative Dyspnea Assessment positions

          -  Severe pulmonary congestion as evidenced by jugular venous distention or lower
             extremity/sacral edema or rales upon chest auscultation or chest x-ray.

          -  BNP > 400 or NT-pro BNP > 1500 drawn during Screening

          -  Systolic blood pressure >= 100 mmHg to < 180 mmHg at time of start of study drug

          -  Serum sodium value >= 115 mEq/L (115 mmol/L) and < 135 mEq/L (135 mmol/L) during
             Screening

        Exclusion Criteria:

          -  Clinical evidence of volume depletion

          -  Active ongoing acute coronary syndrome or acute ST segment elevation myocardial
             infarction (or has experienced a myocardial infarction within 30 days of Screening)

          -  In cardiogenic shock

          -  Calculated creatinine clearance < 30 mL/min/1.73 m2 as estimated by the Modification
             of Diet in Renal Disease (MDRD) equation, has received intravenous (IV) contrast agent
             within 72 hours prior to randomization or is expected to receive IV contrast agent
             within the first 72 hours of study participation

          -  Ultrafiltration within the past 72 hours.

          -  Currently using or expected to use inotropic therapy

          -  Cardiac bypass grafts in the past 60 days

          -  Cerebrovascular accident in the past 30 days

          -  Uncontrolled brady- or ventricular tachyarrhythmias requiring emergent pacemaker
             placement or treatment

          -  Hemodynamically significant uncorrected primary cardiac valvular disease or
             hypertrophic cardiomyopathy

          -  Untreated severe hypothyroidism, hyperthyroidism or adrenal insufficiency based on
             medical history

          -  ALT or AST elevations > 5 times upper limit of normal

          -  Biliary liver cirrhosis, history or presence of severe hepatic encephalopathy,
             ascites, esophageal variceal bleeding within the past three months, severe portal
             hypertension or surgical portosystemic shunt.

          -  Received any organ transplant, clinical diagnosis of pneumonia, symptomatic
             hyponatremia requiring urgent intervention or any concurrent illness which, in the
             opinion of the investigator, may interfere with treatment or evaluation of safety

          -  Pregnant or lactating

          -  Currently using vasopressin, oxytocin or desmopressin