Safety and Efficacy of Conivaptan in Hyponatremic Patients With Symptomatic Acute Decompensated Heart Failure (ADHF)

NCT00843986 | Terminated Phase 3 Results

• 1 other identifier: 087-CL-301
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

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).

Conditions

Hyponatremia; Acute Decompensated Heart Failure

Keywords

hyponatremia; euvolemic hyponatremia; hypervolemic hyponatremia; acute decompensated heart failure; conivaptan; Vaprisol

Outcome Measures

Primary Outcomes (2)

• Change in Renal Function From Baseline at 72 Hours Assessed by Calculated Creatinine Clearance (MDRD Equation)

  MDRD = Modification of Diet in Renal Disease The MDRD equation is a standard calculation for estimated glomerular filtration rate. Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.

  Baseline and 72 Hours

• Assessment of Dyspnea at 24 Hours as Determined by a 7-point Likert Scale

  Dyspnea is defined as the sensation of uncomfortable or difficult breathing. Changes in Dyspnea were assessed using the following 7-point scale: 1-Markedly worse; 2-Moderately worse; 3-Mildly worse; 4-No change; 5-Mildly improved; 6-Moderately improved; 7-Markedly better/improved. Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.

  24 Hours

Secondary Outcomes (9)

• Change in Renal Function From Baseline at Hours 24, 48 and 72 as Assessed by Urine Creatinine Clearance

  Baseline, 24 Hours, 48 Hours and 72 Hours

• 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

  Baseline, 24 Hours, 48 Hours and Day 9

• Incidence of Use of Rescue Therapy or Other Intervention (Including Dialysis) Because of Worsening Renal Function

  Day 9

• Termination of Study Drug Due to an Adverse Event or Intolerability

  48.5 Hours

• Assessment of Dyspnea at Baseline, Hours 6, 12, 24 and 48 Using a Relative Dyspnea Assessment

  Baseline, 6 Hours, 12 Hours, 24 Hours and 48 Hours

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching loading dose and continuous intravenous infusion for 48 hours

Drug: placebo

Conivaptan

EXPERIMENTAL

20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours

Drug: conivaptan

Interventions

conivaptan DRUG

Premix bag

Also known as: Vaprisol; YM087

Conivaptan

placebo DRUG

Premix bag

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cumberland Pharmaceuticals: lead

Study Sites (4)

Unknown Facility

Hyderabaad, 500063, India

Location

Unknown Facility

Karnāl, 132001, India

Location

Unknown Facility

New Delhi, 110025, India

Location

Unknown Facility

New Delhi, 110060, India

Location

Related Links

• Link to Prescribing Information

MeSH Terms

Conditions

Hyponatremia

Interventions

conivaptan

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

The study was terminated because of difficulties in enrolling eligible patients per the protocol inclusion and exclusion criteria. Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.

Results Point of Contact

• Title: Medical Director
• Organization: Astellas Pharma Global Development

clinicaltrials@us.astellas.com

Study Officials

• Art Wheeler, MD

  Cumberland Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2009
• First Posted: February 13, 2009
• Study Start: April 1, 2009
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: May 15, 2014
• Results First Posted: October 1, 2010

Record last verified: 2014-04

Locations

IN (4)