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

This study has been completed.
Sponsor:
Collaborator:
Cardiokine Biopharma, LLC
Information provided by:
CardioKine Inc.
ClinicalTrials.gov Identifier:
NCT01055912
First received: January 22, 2010
Last updated: June 20, 2011
Last verified: November 2010
  Purpose

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


Condition Intervention Phase
Congestive Heart Failure
Drug: Lixivaptan
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by CardioKine Inc.:

Primary Outcome Measures:
  • To assess the efficacy and safety of lixivaptan treatment in congestive heart failure (CHF) patients with volume expansion. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the effects of lixivaptan treatment in CHF patients with volume expansion. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 170
Study Start Date: January 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01055912

  Show 25 Study Locations
Sponsors and Collaborators
CardioKine Inc.
Cardiokine Biopharma, LLC
  More Information

No publications provided by CardioKine Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cesare Orlandi, MD, SVP, Clinical Development, Cardiokine Bioharma, LLC
ClinicalTrials.gov Identifier: NCT01055912     History of Changes
Other Study ID Numbers: CK-LX2401
Study First Received: January 22, 2010
Last Updated: June 20, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by CardioKine Inc.:
Congestive Heart Failure
Volume Overload

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 30, 2014