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

NCT ID: NCT01055912

Last Updated: 2011-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31

Brief Summary

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

Detailed 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.

Conditions

Congestive Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Lixivaptan

Capsule, 100mg Lixivaptan or matching placebo once daily.

Group Type: EXPERIMENTAL

Lixivaptan

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients will be screened for entry into the study and will be randomized (2:1) to lixivaptan or placebo.

Interventions

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.

Intervention Type: DRUG

Placebo

Patients will be screened for entry into the study and will be randomized (2:1) to lixivaptan or placebo.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cardiokine Biopharma, LLC

INDUSTRY

Sponsor Role: collaborator

CardioKine Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Cardiokine Bioharma, LLC

Locations

Mobile Heart Specialists, PC

Mobile, Alabama, United States

Phoenix Clinical

Phoenix, Arizona, United States

Nea Clinic

Jonesboro, Arkansas, United States

Capitol Interventional Cardiology

Carmichael, California, United States

Merced Heart Associates

Merced, California, United States

Orange County Heart Institute and Research Center

Orange, California, United States

Innovative Research of West Florida, Inc

Clearwater, Florida, United States

Edgewater Medical Research Inc

Edgewater, Florida, United States

Foundation/Research/Cardiovascular Specialists Lower Keys

Key West, Florida, United States

Charlotte Heart Group Research Center

Port Charlotte, Florida, United States

Tampa Clinical Research

Tampa, Florida, United States

Executive Health and Research Associates, Inc

Atlanta, Georgia, United States

In-Quest Medical Research, LLC

Duluth, Georgia, United States

Fox Valley Clinical Research Center

Aurora, Illinois, United States

Maine Research Associates

Auburn, Maine, United States

Primary Care Cardiology Research, Inc

Ayer, Massachusetts, United States

Horizon Research

St Louis, Missouri, United States

Great Lakes Medical Research

Westfield, New York, United States

Raleigh Cardiology

Raleigh, North Carolina, United States

Clinical Research Limited

Canton, Ohio, United States

Dayton Heart Center

Dayton, Ohio, United States

Cardiovascular Research Institute of Dallas

Dallas, Texas, United States

East Texas Cardiology

Houston, Texas, United States

National Clinical Research - Norfolk, Inc.

Norfolk, Virginia, United States

National Clinical Research - Richmond

Richmond, Virginia, United States

Countries

United States

References

Ghali JK, Orlandi C, Abraham WT; CK-LX2401 Study Investigators. The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study. Eur J Heart Fail. 2012 Jun;14(6):642-51. doi: 10.1093/eurjhf/hfs051. Epub 2012 Apr 17.

Reference Type: DERIVED

PMID: 22510424 (View on PubMed)

Other Identifiers

CK-LX2401

Identifier Type: -

Identifier Source: org_study_id