Clinical trial NCT00843986: Safety and Efficacy of Conivaptan in Hyponatremic Patients With Symptomatic Acute Decompensated Heart Failure (ADHF)
Official title: A Phase-3b, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Safety and Efficacy of Conivaptan in Symptomatic Acute Decompensated Heart Failure (ADHF) Subjects With Hyponatremia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hyponatremia
Acute Decompensated Heart Failure
Keywords: hyponatremia
euvolemic hyponatremia
hypervolemic hyponatremia
acute decompensated heart failure
conivaptan
Vaprisol
Lead sponsor: Cumberland Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2009-02-13
Enrollment: 9
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: This study will evaluate the safety and effectiveness of Conivaptan, a vasopressin antagonist, in the treatment of hyponatremic subjects having symptomatic acute decompensated heart failure (ADHF).

Detailed description: Subjects will be recruited from the Emergency Department. It is expected that subjects will be treated according to the institution's accepted conventional therapy protocol for the treatment of ADHF. Therapy may also include the use of loop diuretics for the relief of pulmonary congestion and maintenance of adequate urine output.

Eligibility criteria: Inclusion Criteria:

* Presents to emergency department with documented history of CHF and symptomatic ADHF, will be treated for ADHF, and primary reason for admission to the hospital is ADHF
* Dyspnea at rest or with minimal exertion and must have moderate shortness of breath (SOB) in any of the first three Provocative Dyspnea Assessment positions
* Severe pulmonary congestion as evidenced by jugular venous distention or lower extremity/sacral edema or rales upon chest auscultation or chest x-ray.
* BNP \> 400 or NT-pro BNP \> 1500 drawn during Screening
* Systolic blood pressure \>= 100 mmHg to \< 180 mmHg at time of start of study drug
* Serum sodium value \>= 115 mEq/L (115 mmol/L) and \< 135 mEq/L (135 mmol/L) during Screening

Exclusion Criteria:

* Clinical evidence of volume depletion
* Active ongoing acute coronary syndrome or acute ST segment elevation myocardial infarction (or has experienced a myocardial infarction within 30 days of Screening)
* In cardiogenic shock
* Calculated creatinine clearance \< 30 mL/min/1.73 m2 as estimated by the Modification of Diet in Renal Disease (MDRD) equation, has received intravenous (IV) contrast agent within 72 hours prior to randomization or is expected to receive IV contrast agent within the first 72 hours of study participation
* Ultrafiltration within the past 72 hours.
* Currently using or expected to use inotropic therapy
* Cardiac bypass grafts in the past 60 days
* Cerebrovascular accident in the past 30 days
* Uncontrolled brady- or ventricular tachyarrhythmias requiring emergent pacemaker placement or treatment
* Hemodynamically significant uncorrected primary cardiac valvular disease or hypertrophic cardiomyopathy
* Untreated severe hypothyroidism, hyperthyroidism or adrenal insufficiency based on medical history
* ALT or AST elevations \> 5 times upper limit of normal
* Biliary liver cirrhosis, history or presence of severe hepatic encephalopathy, ascites, esophageal variceal bleeding within the past three months, severe portal hypertension or surgical portosystemic shunt.
* Received any organ transplant, clinical diagnosis of pneumonia, symptomatic hyponatremia requiring urgent intervention or any concurrent illness which, in the opinion of the investigator, may interfere with treatment or evaluation of safety
* Pregnant or lactating
* Currently using vasopressin, oxytocin or desmopressin

Primary outcomes:
measure: Change in Renal Function From Baseline at 72 Hours Assessed by Calculated Creatinine Clearance (MDRD Equation)
timeFrame: Baseline and 72 Hours
measure: Assessment of Dyspnea at 24 Hours as Determined by a 7-point Likert Scale
timeFrame: 24 Hours
Secondary outcomes:
measure: Change in Renal Function From Baseline at Hours 24, 48 and 72 as Assessed by Urine Creatinine Clearance
timeFrame: Baseline, 24 Hours, 48 Hours and 72 Hours
measure: Change in Renal Function From Baseline at Hours 24, 48 and Day 9 (or Day of Discharge) as Assessed by Serum Creatinine Concentration and Calculated Creatinine Clearance
timeFrame: Baseline, 24 Hours, 48 Hours and Day 9
measure: Incidence of Use of Rescue Therapy or Other Intervention (Including Dialysis) Because of Worsening Renal Function
timeFrame: Day 9
measure: Termination of Study Drug Due to an Adverse Event or Intolerability
timeFrame: 48.5 Hours
measure: Assessment of Dyspnea at Baseline, Hours 6, 12, 24 and 48 Using a Relative Dyspnea Assessment
timeFrame: Baseline, 6 Hours, 12 Hours, 24 Hours and 48 Hours
measure: Assessment of Dyspnea at Baseline, Hours 6, 12, 24 and 48 Using a Provocative Dyspnea Assessment
timeFrame: Baseline, 6 Hours, 12 Hours, 24 Hours and 48 Hours
measure: Change From Baseline in Body Weight at Hours 24, 48 and 72 and Days 6 and 9 (or Day of Discharge)
timeFrame: Baseline, 24 Hours, 48 Hours, 72 Hours, Day 6 and Day 9
measure: Total Loop Diuretic Use Through 48 Hours
timeFrame: 48 Hours
measure: Total Urine Output at Hours 6, 12, 24, 48 and 72
timeFrame: 6 Hours, 12 Hours, 24 Hours, 48 Hours and 72 Hours
Other outcomes:
Locations:
city: Hyderabaad
country: India
city: Karnal
country: India
city: New Delhi
country: India
city: New Delhi
country: India
Study officials:
affiliation: Cumberland Pharmaceuticals, Inc.
name: Art Wheeler, MD
role: STUDY_DIRECTOR
References: