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

Hyponatremia Clinical Trial

— CONVERT-H  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00843986
• Other study ID #: 087-CL-301
• Status: Terminated
• Phase: Phase 3
• First received: February 11, 2009
• Last updated: April 30, 2014
• Start date: April 2009
• Est. completion date: August 2009

Study information

• Verified date: April 2014
• Source: Cumberland Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaIsrael: Ministry of HealthIndia: Drugs Controller General of India
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Heart Failure
• Hyponatremia

Intervention

Drug:
• conivaptan
Premix bag
• placebo
Premix bag

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cumberland Pharmaceuticals

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	No
Secondary	Change in Renal Function From Baseline at Hours 24, 48 and 72 as Assessed by Urine Creatinine Clearance	Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.	Baseline, 24 Hours, 48 Hours and 72 Hours	Yes
Secondary	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	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	Yes
Secondary	Incidence of Use of Rescue Therapy or Other Intervention (Including Dialysis) Because of Worsening Renal Function	Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.	Day 9	Yes
Secondary	Termination of Study Drug Due to an Adverse Event or Intolerability	Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.	48.5 Hours	Yes
Secondary	Assessment of Dyspnea at Baseline, Hours 6, 12, 24 and 48 Using a Relative Dyspnea Assessment	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	No
Secondary	Assessment of Dyspnea at Baseline, Hours 6, 12, 24 and 48 Using a Provocative Dyspnea Assessment	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	No
Secondary	Change From Baseline in Body Weight at Hours 24, 48 and 72 and Days 6 and 9 (or Day of Discharge)	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	No
Secondary	Total Loop Diuretic Use Through 48 Hours	Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.	48 Hours	No
Secondary	Total Urine Output at Hours 6, 12, 24, 48 and 72	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	No

External Links

•   Link to Prescribing Information