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

April 30, 2014 updated by: Cumberland Pharmaceuticals

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

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).

Study Overview

Status

Terminated

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Hyderabaad, India, 500063
      • Karnal, India, 132001
      • New Delhi, India, 110060
      • New Delhi, India, 110025

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Matching loading dose and continuous intravenous infusion for 48 hours
Premix bag
Experimental: Conivaptan
20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Premix bag
Other Names:
  • Vaprisol; YM087

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Renal Function From Baseline at 72 Hours Assessed by Calculated Creatinine Clearance (MDRD Equation)
Time Frame: Baseline and 72 Hours

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
Time Frame: 24 Hours

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Renal Function From Baseline at Hours 24, 48 and 72 as Assessed by Urine Creatinine Clearance
Time Frame: Baseline, 24 Hours, 48 Hours and 72 Hours
Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
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
Time Frame: Baseline, 24 Hours, 48 Hours and Day 9

Calculated creatinine clearance is only calculated through hour 72 using the 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, 24 Hours, 48 Hours and Day 9
Incidence of Use of Rescue Therapy or Other Intervention (Including Dialysis) Because of Worsening Renal Function
Time Frame: Day 9
Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
Day 9
Termination of Study Drug Due to an Adverse Event or Intolerability
Time Frame: 48.5 Hours
Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
48.5 Hours
Assessment of Dyspnea at Baseline, Hours 6, 12, 24 and 48 Using a Relative Dyspnea Assessment
Time Frame: Baseline, 6 Hours, 12 Hours, 24 Hours and 48 Hours

Dyspnea is defined as the sensation of uncomfortable or difficult breathing.

Changes in Dyspnea were assessed using the following 7-point Likert 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.

Baseline, 6 Hours, 12 Hours, 24 Hours and 48 Hours
Assessment of Dyspnea at Baseline, Hours 6, 12, 24 and 48 Using a Provocative Dyspnea Assessment
Time Frame: Baseline, 6 Hours, 12 Hours, 24 Hours and 48 Hours

Dyspnea is defined as the sensation of uncomfortable or difficult breathing.

The Provocative Dyspnea Assessment assesses dyspnea and changes in dyspnea from Baseline on a 5-point Likert scale at 5 different positions and assigns a Dyspnea Severity Score that ranges from 1 (worst severity) to 25 (least severity).

Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.

Baseline, 6 Hours, 12 Hours, 24 Hours and 48 Hours
Change From Baseline in Body Weight at Hours 24, 48 and 72 and Days 6 and 9 (or Day of Discharge)
Time Frame: Baseline, 24 Hours, 48 Hours, 72 Hours, Day 6 and Day 9
Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
Baseline, 24 Hours, 48 Hours, 72 Hours, Day 6 and Day 9
Total Loop Diuretic Use Through 48 Hours
Time Frame: 48 Hours
Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
48 Hours
Total Urine Output at Hours 6, 12, 24, 48 and 72
Time Frame: 6 Hours, 12 Hours, 24 Hours, 48 Hours and 72 Hours
Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
6 Hours, 12 Hours, 24 Hours, 48 Hours and 72 Hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Art Wheeler, MD, Cumberland Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

August 1, 2009

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

February 11, 2009

First Submitted That Met QC Criteria

February 11, 2009

First Posted (Estimate)

February 13, 2009

Study Record Updates

Last Update Posted (Estimate)

May 15, 2014

Last Update Submitted That Met QC Criteria

April 30, 2014

Last Verified

April 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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