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

• Sponsor: Cumberland Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00843986
• Collaborator: (none)
• Enrollment: 9
• Locations: 4
• Arms: 2
• Duration (Months): 4
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Hyponatremia; Acute Decompensated Heart Failure	Drug: conivaptan; Drug: placebo	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, 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
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Vaprisol; YM087

Outcome Measures

Primary Outcome Measures

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

2. Assessment of Dyspnea at 24 Hours as Determined by a 7-point Likert Scale [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.

Secondary Outcome Measures

1. 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]

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

2. 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]

   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.

3. Incidence of Use of Rescue Therapy or Other Intervention (Including Dialysis) Because of Worsening Renal Function [Day 9]

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

4. Termination of Study Drug Due to an Adverse Event or Intolerability [48.5 Hours]

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

5. 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]

   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.

6. Assessment of Dyspnea at Baseline, Hours 6, 12, 24 and 48 Using a Provocative Dyspnea Assessment [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.

7. Change From Baseline in Body Weight at Hours 24, 48 and 72 and Days 6 and 9 (or Day of Discharge) [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.

8. Total Loop Diuretic Use Through 48 Hours [48 Hours]

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

9. Total Urine Output at Hours 6, 12, 24, 48 and 72 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1		Hyderabaad		India	500063
2		Karnal		India	132001
3		New Delhi		India	110025
4		New Delhi		India	110060

Sponsors and Collaborators

• Cumberland Pharmaceuticals

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Link to Prescribing Information

Publications

None provided.

• Responsible Party: Cumberland Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00843986
• Other Study ID Numbers: 087-CL-301
• First Posted: Feb 13, 2009
• Last Update Posted: May 15, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Cumberland Pharmaceuticals: hyponatremia; euvolemic hyponatremia; hypervolemic hyponatremia; acute decompensated heart failure; conivaptan; Vaprisol
• Additional relevant MeSH terms: Heart Failure; Hyponatremia; Conivaptan

Study Results

Participant Flow

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Period Title: Overall Study
STARTED	3	6
Completed Treatment (Infusion)	2	6
COMPLETED	2	5
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Placebo	Conivaptan	Total
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours	Total of all reporting groups
Overall Participants	3	6	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.7 (13.05)	65.8 (7.78)	62.8 (10.07)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 16.7%	2 22.2%
Male	2 66.7%	5 83.3%	7 77.8%
Race/Ethnicity, Customized (participants) [Number]
Asian	3 100%	6 100%	9 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

2. Primary Outcome

Title	Assessment of Dyspnea at 24 Hours as Determined by a 7-point Likert Scale
Description	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.
Time Frame	24 Hours

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

4. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline, 24 Hours, 48 Hours and Day 9

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

5. Secondary Outcome

Title	Incidence of Use of Rescue Therapy or Other Intervention (Including Dialysis) Because of Worsening Renal Function
Description	Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
Time Frame	Day 9

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

6. Secondary Outcome

Title	Termination of Study Drug Due to an Adverse Event or Intolerability
Description	Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
Time Frame	48.5 Hours

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

7. Secondary Outcome

Title	Assessment of Dyspnea at Baseline, Hours 6, 12, 24 and 48 Using a Relative Dyspnea Assessment
Description	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.
Time Frame	Baseline, 6 Hours, 12 Hours, 24 Hours and 48 Hours

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

9. Secondary Outcome

Title	Change From Baseline in Body Weight at Hours 24, 48 and 72 and Days 6 and 9 (or Day of Discharge)
Description	Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
Time Frame	Baseline, 24 Hours, 48 Hours, 72 Hours, Day 6 and Day 9

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

10. Secondary Outcome

Title	Total Loop Diuretic Use Through 48 Hours
Description	Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
Time Frame	48 Hours

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

11. Secondary Outcome

Title	Total Urine Output at Hours 6, 12, 24, 48 and 72
Description	Outcome Measures were not analyzed due to the abbreviated enrollment at early study termination.
Time Frame	6 Hours, 12 Hours, 24 Hours, 48 Hours and 72 Hours

Outcome Measure Data

Analysis Population Description

Study was terminated - assessment of this Outcome Measure was not performed.

Arm/Group Title	Placebo	Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours	20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
Measure Participants	0	0

Adverse Events

Time Frame	Adverse Event collection will begin at the start of study drug infusion and continue through Day 9/ Day of Discharge.
Adverse Event Reporting Description	Treatment Emergent Adverse Events are reported and are defined as Adverse Events recorded during the treatment and follow-up periods of the study.
Arm/Group Title	Placebo		Conivaptan
Arm/Group Description	Matching loading dose and continuous intravenous infusion for 48 hours		20mg loading dose followed by a 20mg/ day continuous intravenous infusion for 48 hours
All Cause Mortality
	Placebo		Conivaptan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Conivaptan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		1/6 (16.7%)
Cardiac disorders
Cardiac arrest	0/3 (0%)		1/6 (16.7%)
Cardiac failure	1/3 (33.3%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Conivaptan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		5/6 (83.3%)
Cardiac disorders
Atrial flutter	0/3 (0%)		1/6 (16.7%)
Ventricular tachycardia	0/3 (0%)		1/6 (16.7%)
Gastrointestinal disorders
Constipation	0/3 (0%)		1/6 (16.7%)
General disorders
Infusion site erythema	0/3 (0%)		3/6 (50%)
Infusion site pain	0/3 (0%)		1/6 (16.7%)
Pyrexia	0/3 (0%)		1/6 (16.7%)
Investigations
Heart rate increased	0/3 (0%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Muscle spasms	0/3 (0%)		1/6 (16.7%)
Pain in extremity	0/3 (0%)		1/6 (16.7%)
Nervous system disorders
Headache	0/3 (0%)		1/6 (16.7%)
Vascular disorders
Hypotension	1/3 (33.3%)		0/6 (0%)

Limitations/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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document. Sponsor may delay the publication for an additional 60 days to seek patent protection.