Study to Evaluate the Effects of Oral Administration of Lixivaptan in Patients With Congestive Heart Failure

Congestive Heart Failure Clinical Trial

Official title:

Multicenter, Randomized, Double-Blind, Placebo- Controlled, Parallel Group, Efficacy and Safety Study to Evaluate the Effects of Oral Administration of Lixivaptan in Patients With Congestive Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01055912
• Other study ID #: CK-LX2401
• Status: Completed
• Phase: Phase 2
• First received: January 22, 2010
• Last updated: June 20, 2011
• Start date: January 2010

Study information

• Verified date: November 2010
• Source: CardioKine Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effects of oral lixivaptan capsules in patients with congestive heart failure.

Description:

Diuretics are used extensively in the treatment of patients with CHF, and their efficacy is well established. However, there is a tendency for currently used diuretics to increase afterload and deplete electrolytes, and in many patients ventricular function continues to deteriorate over time.

Loop diuretics, such as furosemide, also have known negative effects on renal function reducing the glomerular filtration rate, and have been shown to activate the RAA system.

Lixivaptan is a potent, non-peptide selective antagonist of the vasopressin V2 receptor.

Lixivaptan treatment results in increased free water excretion, thus decreasing urine osmolality, increasing urine flow, and increasing serum osmolality. Short-term treatment with lixivaptan has demonstrated improved fluid management and electrolyte balance in HF patients.

This study was designed to assess the effects of vasopressin blockade with lixivaptan in patients with CHF with volume overload. A placebo-control arm will allow for assessment of the effect of lixivaptan in addition to standard diuretic therapy as compared with standard diuretic therapy alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ability to understand the purpose and risks of the study and to provide signed and dated informed consent.

• Men and women aged 18 years or older.

• History of chronic CHF defined as requiring standard HF treatment (including diuretics) for a minimum of 30 days.

• Documented LVEF by any method within 12 months prior to screening.

• The patient has clinical evidence of volume overload at the time of inclusion with at least one of the following:

• Dyspnea

• Pulmonary congestion (rales)

• Peripheral edema

• Increased jugular venous pressure and/or hepatic congestion with ascites

• Chest x-ray consistent with CHF

• Plasma brain natriuretic peptide (BNP) =150 pg/mL or N-terminal prohormone brain natriuretic peptide (NT pro-BNP) =450 pg/mL

Exclusion Criteria:

• Women who are pregnant (positive pregnancy test), breastfeeding, or who will not adhere to the reproductive precautions as outlined in this protocol and in the informed consent form (ICF).

• Sustained (three blood pressure measurements over 1 hour) systolic blood pressure <90 mmHg at Screening or Day 0.

• ST segment elevation myocardial infarction or stroke within 30 days prior to Screening.

• Hemodynamically destabilizing cardiac arrhythmia within 30 days prior to Day 0.

• Clinically significant valvular disease.

• Known clinically significant obstructive, restrictive, or hypertrophic cardiomyopathy.

• Cardiac surgery or percutaneous coronary intervention within 30 days prior to Day 0.

• Major surgical procedure within 7 days prior to Day 0.

• Likely to undergo cardiac transplantation, left ventricular assist device (LVAD) or other device implantation, or other cardiac surgery within 3 months after Screening.

• Placement of implantable cardioverter defibrillator or cardiac resynchronization therapy device within 60 days prior to Day 0.

• CHF due to uncorrected thyroid disease, active myocarditis, or known amyloid cardiomyopathy.

• Presence of any clinically significant (as determined by the Investigator) endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, oncologic, and/or other major disease that might interfere with safe and compliant participation in this study.

• Screening laboratory findings as follows:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal

• Total bilirubin >2.0 mg/dL

• Serum creatinine >3.0 mg/dL

• Hemoglobin <9.0 g/dL

• Uncontrolled diabetes mellitus as defined by the Investigator (e.g., glycosylated hemoglobin [HbA1c] >9%).

• History of chronic drug/medication abuse within the past 6 months; or current alcohol abuse.

• Co-morbid condition with an expected survival of less than 3 months.

• Known allergy to any vasopressin antagonist or any condition for which treatment with a vasopressin antagonist may present undue risk to the patient.

• Current or recent administration (within 7 days of Day 0) of prohibited medications as listed in Section 8.6.4 .

• Participation in any other investigational study of drugs or devices within 30 days prior to Screening.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• Lixivaptan
Capsule. Patients will be screened for entry into the study and will be randomized (2:1) to lixivaptan or placebo. One hundred (100) patients will be randomized to receive lixivaptan 100 mg once daily (QD) for 8 weeks. Fifty (50) placebo patients will receive matching oral placebo for 8 weeks.
• Placebo
Patients will be screened for entry into the study and will be randomized (2:1) to lixivaptan or placebo.

Locations

Country	Name	City	State
United States	Executive Health and Research Associates, Inc	Atlanta	Georgia
United States	Maine Research Associates	Auburn	Maine
United States	Fox Valley Clinical Research Center	Aurora	Illinois
United States	Primary Care Cardiology Research, Inc	Ayer	Massachusetts
United States	Clinical Research Limited	Canton	Ohio
United States	Capitol Interventional Cardiology	Carmichael	California
United States	Innovative Research of West Florida, Inc	Clearwater	Florida
United States	Cardiovascular Research Institute of Dallas	Dallas	Texas
United States	Dayton Heart Center	Dayton	Ohio
United States	In-Quest Medical Research, LLC	Duluth	Georgia
United States	Edgewater Medical Research Inc	Edgewater	Florida
United States	East Texas Cardiology	Houston	Texas
United States	Nea Clinic	Jonesboro	Arkansas
United States	Foundation/Research/Cardiovascular Specialists Lower Keys	Key West	Florida
United States	Merced Heart Associates	Merced	California
United States	Mobile Heart Specialists, PC	Mobile	Alabama
United States	National Clinical Research - Norfolk, Inc.	Norfolk	Virginia
United States	Orange County Heart Institute and Research Center	Orange	California
United States	Phoenix Clinical	Phoenix	Arizona
United States	Charlotte Heart Group Research Center	Port Charlotte	Florida
United States	Raleigh Cardiology	Raleigh	North Carolina
United States	National Clinical Research - Richmond	Richmond	Virginia
United States	Horizon Research	St. Louis	Missouri
United States	Tampa Clinical Research	Tampa	Florida
United States	Great Lakes Medical Research	Westfield	New York

Sponsors (2)

Lead Sponsor	Collaborator
CardioKine Inc.	Cardiokine Biopharma, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the efficacy and safety of lixivaptan treatment in congestive heart failure (CHF) patients with volume expansion.		8 weeks	Yes
Secondary	To assess the effects of lixivaptan treatment in CHF patients with volume expansion.		8 weeks	Yes