Clinical trial NCT00876876: International, Multicenter, Open-Label and Randomized Withdrawal Study of Oral Lixivaptan in Heart Failure Patients With Chronic Hyponatremia
Official title: International, Multicenter, Open-Label and Randomized Withdrawal Study of Oral Lixivaptan in Heart Failure Patients With Chronic Hyponatremia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Hypervolemic Hyponatremia
Keywords: hypervolemic hyponatremia
serum sodium
fluid overload
heartfailure
acute heart failure
vasopressin antagonist
Lead sponsor: CardioKine Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cardiokine Biopharma, LLC
name: Biogen
First posted: 2009-04-07
Enrollment: 300
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: To demonstrate that after 12 weeks of open-label lixivaptan treatment, serum sodium is maintained in hyponatremic patients continuing to receive lixivaptan compared to placebo during the 4 week double blind treatment period.


Eligibility criteria: Inclusion Criteria:

1. Men and Women with age greater than or equal to 18 years.
2. Prior successful participation in a randomized, blinded, placebo-controlled Phase 3 lixivaptan study of hyponatremia in Heart Failure (Protocol CK-LX3401) with evidence of continued need for therapy as follows:

   * Patient completed full course of treatment (e.g., either placebo or lixivaptan). Treatment assignments for Protocol CK-LX3401 will not be unblinded prior to participation in the extension study.
   * Baseline serum sodium concentration \< 135 mEq/L following a 30 day post treatment follow-up period in a lixivaptan hyponatremia parent trial. Repeat measures of serum sodium are allowed; the last serum sodium result within 24 hours prior to randomization will serve as the qualifying measurement.
3. The patient has clinical evidence of volume overload 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; OR
   * Plasma BNP ≥150 pg/mL or NT pro-BNP ≥ 450 pg/mL

Exclusion Criteria:

1. 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.
2. Inability to provide informed consent.
3. Acute severe hyponatremia with overt symptoms of hyponatremia requiring immediate medical intervention (e.g., coma, seizures).
4. Acute or transient hyponatremia (e.g., associated with head trauma or postoperative state).
5. Hyponatremia in hypovolemic states. Hypovolemia is defined as the presence of clinical evidence of fluid volume depletion.
6. Euvolemic Hyponatremia (e.g., SIADH, etc.). Euvolemic hyponatremia is defined as low serum sodium in the presence of normal total body sodium due to mild to moderate increases in total body water without edema.

Primary outcomes:
measure: To demonstrate that after 12 weeks of open-label lixivaptan treatment, serum sodium is maintained in hyponatremic patients continuing to receive lixivaptan compared to placebo during the 4 week double blind treatment period.
timeFrame: 12 weeks
Secondary outcomes:
measure: To demonstrate that after 12 weeks of open-label lixivaptan treatment, improvements in the time to complete the Trail Making Test (Part B) will be maintained in patients continuing to receive lixivaptan.
timeFrame: 20 weeks
Other outcomes:
Locations:
Study officials:
References: