Clinical trial NCT01055912: Study to Evaluate the Effects of Oral Administration of Lixivaptan in Patients With Congestive Heart Failure
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congestive Heart Failure
Keywords: Congestive Heart Failure
Volume Overload
Lead sponsor: CardioKine Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cardiokine Biopharma, LLC
First posted: 2010-01-26
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To assess the efficacy and safety of lixivaptan treatment in congestive heart failure (CHF) patients with volume expansion.
timeFrame: 8 weeks
Secondary outcomes:
measure: To assess the effects of lixivaptan treatment in CHF patients with volume expansion.
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Heart Specialists, PC
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Clinical
state: Arizona
city: Jonesboro
country: United States
facility: Nea Clinic
state: Arkansas
city: Carmichael
country: United States
facility: Capitol Interventional Cardiology
state: California
city: Merced
country: United States
facility: Merced Heart Associates
state: California
city: Orange
country: United States
facility: Orange County Heart Institute and Research Center
state: California
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc
state: Florida
city: Edgewater
country: United States
facility: Edgewater Medical Research Inc
state: Florida
city: Key West
country: United States
facility: Foundation/Research/Cardiovascular Specialists Lower Keys
state: Florida
city: Port Charlotte
country: United States
facility: Charlotte Heart Group Research Center
state: Florida
city: Tampa
country: United States
facility: Tampa Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Executive Health and Research Associates, Inc
state: Georgia
city: Duluth
country: United States
facility: In-Quest Medical Research, LLC
state: Georgia
city: Aurora
country: United States
facility: Fox Valley Clinical Research Center
state: Illinois
city: Auburn
country: United States
facility: Maine Research Associates
state: Maine
city: Ayer
country: United States
facility: Primary Care Cardiology Research, Inc
state: Massachusetts
city: St. Louis
country: United States
facility: Horizon Research
state: Missouri
city: Westfield
country: United States
facility: Great Lakes Medical Research
state: New York
city: Raleigh
country: United States
facility: Raleigh Cardiology
state: North Carolina
city: Canton
country: United States
facility: Clinical Research Limited
state: Ohio
city: Dayton
country: United States
facility: Dayton Heart Center
state: Ohio
city: Dallas
country: United States
facility: Cardiovascular Research Institute of Dallas
state: Texas
city: Houston
country: United States
facility: East Texas Cardiology
state: Texas
city: Norfolk
country: United States
facility: National Clinical Research - Norfolk, Inc.
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research - Richmond
state: Virginia
Study officials:
References:
citation: 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.