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

NCT00806910 | Withdrawn Phase 4

• 1 other identifier: HN-4040
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Heart Failure

Keywords

Heart Failure; conivaptan; Diuresis

Outcome Measures

Primary Outcomes (1)

• Degree of diuresis as measured by weight change and intake and output measurement

  Post infusion, Pre discharge and at 30 day Post discharge

Secondary Outcomes (7)

• Length of stay (LOS) in hospital

  Concurrent

• Clinical status based on NYHA criteria

  Pre-discharge and 30-day post-discharge follow up

• Serum electrolytes

  Pre and Post infusion

• BUN and Serum Creatinine concentration

  Post infusion, Pre discharge and at 30 day Post discharge

• Number of readmissions due to ADHF

  Within 30-day post-discharge follow up

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Subjects will be treated with Intravenous Vaprisol along with Nesiritide infusion and intravenous Furosemide (either continuous infusion or bolus injections - total dose of Furosemide received will be calculated at the end of the study).

Drug: Conivaptan

Placebo

PLACEBO COMPARATOR

Subjects will be given Placebo (at the same rate of Vaprisol given in the treatment arm) along with Nesiritide infusion and intravenous Furosemide (either continuous infusion or bolus injections - total dose of Furosemide received will be calculated at the end of the study).

Other: Placebo

Interventions

Conivaptan DRUG

IV Vaprisol initially at 20 mg IV injection over 30 minutes, followed by a 20 mg IV infusion over the next 24 hours (i.e. 20 mg bolus, 20 mg continuous infusion approximately 24 hrs).

Also known as: Vaprisol

Treatment

Placebo OTHER

Placebo (will be given at the same rate of Vaprisol given in the treatment arm)

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Albert Einstein Healthcare Network: lead
• Astellas Pharma Inc: collaborator

MeSH Terms

Conditions

Heart Failure

Interventions

conivaptan; Sodium Chloride

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Darshak H Karia, MD

  Albert Einstein Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 10, 2008
• First Posted: December 11, 2008
• Study Start: October 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: June 23, 2011

Record last verified: 2011-06