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

Sponsor

CardioKine Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01055912

Collaborator

Cardiokine Biopharma, LLC (Industry)

170

Enrollment

Locations

Arms

6.8

Patients Per Site

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure	Drug: Lixivaptan Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

170 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lixivaptan Capsule, 100mg Lixivaptan or matching placebo once daily.	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 Comparator: Placebo Patients will be screened for entry into the study and will be randomized (2:1) to lixivaptan or placebo.	Drug: Placebo Patients will be screened for entry into the study and will be randomized (2:1) to lixivaptan or placebo.

Arm

Intervention/Treatment

Experimental: Lixivaptan

Capsule, 100mg Lixivaptan or matching placebo once daily.

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 Comparator: Placebo

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

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

To assess the efficacy and safety of lixivaptan treatment in congestive heart failure (CHF) patients with volume expansion. [8 weeks]

Secondary Outcome Measures

To assess the effects of lixivaptan treatment in CHF patients with volume expansion. [8 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mobile Heart Specialists, PC	Mobile	Alabama	United States	36608
2	Phoenix Clinical	Phoenix	Arizona	United States	85029
3	Nea Clinic	Jonesboro	Arkansas	United States	72401
4	Capitol Interventional Cardiology	Carmichael	California	United States	95608
5	Merced Heart Associates	Merced	California	United States	95340
6	Orange County Heart Institute and Research Center	Orange	California	United States	92868
7	Innovative Research of West Florida, Inc	Clearwater	Florida	United States	33756
8	Edgewater Medical Research Inc	Edgewater	Florida	United States	32141
9	Foundation/Research/Cardiovascular Specialists Lower Keys	Key West	Florida	United States	33040
10	Charlotte Heart Group Research Center	Port Charlotte	Florida	United States	33952
11	Tampa Clinical Research	Tampa	Florida	United States	33624
12	Executive Health and Research Associates, Inc	Atlanta	Georgia	United States	30342
13	In-Quest Medical Research, LLC	Duluth	Georgia	United States	30096
14	Fox Valley Clinical Research Center	Aurora	Illinois	United States	60504
15	Maine Research Associates	Auburn	Maine	United States	04210
16	Primary Care Cardiology Research, Inc	Ayer	Massachusetts	United States	01432
17	Horizon Research	St. Louis	Missouri	United States	63141
18	Great Lakes Medical Research	Westfield	New York	United States	14787
19	Raleigh Cardiology	Raleigh	North Carolina	United States	27610
20	Clinical Research Limited	Canton	Ohio	United States	44718
21	Dayton Heart Center	Dayton	Ohio	United States	45414
22	Cardiovascular Research Institute of Dallas	Dallas	Texas	United States	75231
23	East Texas Cardiology	Houston	Texas	United States	77002
24	National Clinical Research - Norfolk, Inc.	Norfolk	Virginia	United States	23502
25	National Clinical Research - Richmond	Richmond	Virginia	United States	23294

Sponsors and Collaborators

CardioKine Inc.
Cardiokine Biopharma, LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT01055912

Other Study ID Numbers:

CK-LX2401

First Posted:

Jan 26, 2010

Last Update Posted:

Jun 28, 2011

Last Verified:

Nov 1, 2010

Keywords provided by , ,

Congestive Heart Failure

Volume Overload

Additional relevant MeSH terms:

Heart Failure

Study Results

No Results Posted as of Jun 28, 2011