Diuretic and Renal Effects of Vaprisol When Administered Along With Furosemide and Nesiritide Continuous Infusion

• Status: Withdrawn
• Trial end date: 2010-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Heart Failure is a growing and challenging public health concern in the United States. Heart failure commonly manifests as a syndrome of salt and water retention. Arginine vasopressin is a peptide hormone that is intimately involved in salt and water homeostasis. AVP is released into the circulation in response low blood volume and hypernatraemia. Despite fluid overload, vasopressin levels are often inappropriately elevated in patients with heart failure and LV dysfunction. Data suggest that vasopressin may also contribute to the deleterious circulatory response in patients with heart failure and play a role in the development and progression of the disease process. In their study, Udelson et al. showed that vasopressin receptor antagonism with Conivaptan resulted in significant diuresis with stable hemodynamics in advanced heart failure patients. Currently Intravenous diuretics and vasodilators are the standard of care in treating patients with acute decompensated heart failure. We will be studying the renal and diuretic effects of add on therapy with intravenous Conivaptan in patients receiving intravenous Nesiritide and intravenous diuretics.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Albert Einstein Healthcare Network
• Collaborator: Astellas Pharma Inc
• Treatments: Conivaptan; Diuretics; Furosemide; Natriuretic Peptide, Brain

Criteria

Inclusion Criteria:

• Patients over the age of 18 and able to consent

• LVEF ≤40% (as measured within last 6 months before entering into the study)

• Patients with Acute Decompensated Heart Failure (ADHF) (NYHA class 3 & 4)

• Patients with estimated GFR >40ml/min as calculated by Cockcroft-Gault or MDRD formula

• Serum Sodium level <135 meq/L

• Ability to understand and willing to sign informed consent

• Willingness to follow-up in the clinic as outpatient

Exclusion Criteria:

• Patients with Acute Coronary Syndrome (ACS: Unstable angina, NSTEMI or STEMI)

• Patients on pressors (including Vasopressin analogs) for hemodynamic stability

• Supine systolic blood pressure <100 mm Hg

• Hypersensitivity to Conivaptan

• Concomitant use of medications that affects hepatic drug metabolism (e.g. Ketoconazole, Itraconazole, Ritonavir, Indinavir, Clarithromycin etc.)

• Significant liver dysfunction (ALT & AST more than twice the upper limit of normal)

• Uncontrolled bradyarrhythmias or tachyarrhythmias

• Pacemaker or defibrillator implantation or other cardiac surgery <60 days

• Severe obstructive pulmonary disease

• Significant uncorrected valvular or congenital heart disease

• Obstructive cardiomyopathy

• Significant renal impairment (defined as a serum creatinine >2.5 mg/dL or creatinine clearance <40 ml/min).

• Radiocontrast infusion within <7 days

• Pregnant or lactating female subject

• Untreated severe hyperthyroidism, hypothyroidism or adrenal insufficiency

• Expected requirement for emergent treatment of hypernatremia during the course of the study

• Known urinary outflow obstruction, unless subject is, or can be catheterized during the study

• Serum albumin < 1.5 gm/dl documented any time during any time during seven days prior to study drug administration

• Any concurrent illness, which in opinion of the investigator, may interfere with treatment or evaluation of safety.

• White blood cell count (WBC) count < 3000 /mL documented any time during seven days prior to study drug administration or anticipated drop in WBC count <3000/mL during the period of study due to chemotherapy.

• Participation in another clinical trial of an investigational drug (including placebo) or device within 30 days of screening for entry into the present study

• Subject has moderate ascites on physical examination secondary to hepatic dysfunction (ascites primarily related to cardiac dysfunction will be allowed as long as subject does not have cardiac cirrhosis).

• Subject has moderate to severe hepatic impairment as evidenced by Child-Pugh B or C criteria.

• Subject has a history of hepatic encephalopathy, hematemesis or melena.

• Subjects with altered mental status due to severe hyponatremia.

• Patient belonging to a vulnerable population such as institutionalized person, prisoners and persons with decisional incapacity or dementia.

• Patients on medications which are known to cause drug interactions such as Nicardipine, lovastatin, Ritonovir, Doxorubicin Etc