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

This study has been terminated.
(The clinical study has been terminated based on difficulties to enroll eligible subjects per protocol inclusion and exclusion criteria.)
Sponsor:
Information provided by (Responsible Party):
Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00843986
First received: February 11, 2009
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
Hyponatremia
Acute Decompensated Heart Failure
Drug: conivaptan
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Cumberland Pharmaceuticals:

Primary Outcome Measures:
  • Change in Renal Function From Baseline at 72 Hours Assessed by Calculated Creatinine Clearance (MDRD Equation) [ Time Frame: Baseline and 72 Hours ] [ Designated as safety issue: Yes ]

    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.


  • Assessment of Dyspnea at 24 Hours as Determined by a 7-point Likert Scale [ Time Frame: 24 Hours ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.

  • 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 ] [ Designated as safety issue: Yes ]

    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.


  • Incidence of Use of Rescue Therapy or Other Intervention (Including Dialysis) Because of Worsening Renal Function [ Time Frame: Day 9 ] [ Designated as safety issue: Yes ]
    Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.

  • Termination of Study Drug Due to an Adverse Event or Intolerability [ Time Frame: 48.5 Hours ] [ Designated as safety issue: Yes ]
    Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.

  • 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 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]
    Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.

  • Total Loop Diuretic Use Through 48 Hours [ Time Frame: 48 Hours ] [ Designated as safety issue: No ]
    Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.

  • Total Urine Output at Hours 6, 12, 24, 48 and 72 [ Time Frame: 6 Hours, 12 Hours, 24 Hours, 48 Hours and 72 Hours ] [ Designated as safety issue: No ]
    Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.


Enrollment: 9
Study Start Date: April 2009
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Matching loading dose and continuous intravenous infusion for 48 hours
Drug: placebo
Premix bag
Experimental: Conivaptan
20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Drug: conivaptan
Premix bag
Other Name: Vaprisol; YM087

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00843986

Locations
India
Hyderabaad, India, 500063
Karnal, India, 132001
New Delhi, India, 110025
New Delhi, India, 110060
Sponsors and Collaborators
Cumberland Pharmaceuticals
Investigators
Study Director: Art Wheeler, MD Cumberland Pharmaceuticals Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00843986     History of Changes
Other Study ID Numbers: 087-CL-301
Study First Received: February 11, 2009
Results First Received: September 9, 2010
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Israel: Ministry of Health
India: Drugs Controller General of India

Keywords provided by Cumberland Pharmaceuticals:
hyponatremia
euvolemic hyponatremia
hypervolemic hyponatremia
acute decompensated heart failure
conivaptan
Vaprisol

Additional relevant MeSH terms:
Heart Failure
Hyponatremia
Heart Diseases
Cardiovascular Diseases
Water-Electrolyte Imbalance
Metabolic Diseases

ClinicalTrials.gov processed this record on September 15, 2014