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Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure

Primary Purpose

Right Heart Failure, Pulmonary Hypertension

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Spironolactone and conivaptan

About this trial

This is an interventional treatment trial for Right Heart Failure

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

1. Patients with World Health Organization (WHO) group 1 pulmonary arterial hypertension [51], excluding patients with portal hypertension, meeting the following hemodynamic parameters:

Mean pulmonary artery pressure (mPAP) >35 mmHg at rest, and
Pulmonary capillary wedge pressure (PCWP) <15 mmHg, and
Pulmonary vascular resistance (PVR) >1.5 wood units, and 2. Age 18 to 75 years 3. Right ventricular failure defined by right atrial pressure >7 mmHg along with either dilated right ventricle, or absence of inferior vena cava collapse or BNP >100 pg/ml 4. Patients of childbearing age must be practicing effective birth control. 5. Normal left ventricular function as assessed by echocardiogram, multiple gated acquisition (MUGA) cardiac scan, or invasive left ventriculography.

Exclusion Criteria:

1. Group 2-5 pulmonary hypertension as defined by WHO.

Pulmonary hypertension with left heart failure (as assessed by echocardiogram, multiple gated acquisition (MUGA) cardiac scan, or invasive left ventriculography).
Pulmonary hypertension associated with lung disease and/or hypoxemia (e.g. chronic obstructive pulmonary disease, interstitial lung disease, sleep disordered breathing, chronic exposure to high altitude, alveolar hypoventilation syndrome.
Pulmonary hypertension due to chronic thrombotic and/or embolic diseases
Miscellaneous such as sarcoidosis, compression of pulmonary vessels by adenopathy, tumor 2. Systemic hypertension, defined as a systolic pressure >140 mmHg or a diastolic blood pressure >90 mmHg 3. Patients taking angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARBs) 4. Pregnancy 5. Chronic kidney disease (serum creatinine > 2.5mg/dl, proteinuria >500 mg/day, hematuria) 6. Cirrhosis or portal hypertension 7. Inability to provide informed consent. 8. Allergy to conivaptan or spironolactone. 9. Active malignancy 10. Patients receiving spironolactone 11. Enrollment in other interventional studies. 12. Patients on Highly Active Antiretroviral Therapy (HAART)

Sites / Locations

University of Colorado at Denver and Health Sciences Center General Clinical Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Usual care

Spironolactone and conivaptan

Arm Description

Group II

Group I

Outcomes

Primary Outcome Measures

Cross sectional study

Correlation between severity of pulmonary hypertension and neurohumoral activation, Regional Blood Flow (RBF) & Transcatheter Pulmonary Valve (TPV). Acute study:electrolyte-free water and sodium excretion. Cohort Study: Composite of Cardiac index (CI),brain natriuretic peptide (BNP) and Right Atrial Pressure (RAP)

Secondary Outcome Measures

Cross-sectional Study

Correlations between mean pulmonary artery pressure, pulmonary vascular resistance; and neurohumoral activation, glomerular filtration rate (GFR) and Transcatheter Pulmonary Valve (TPV). Acute study:correlation between response to drug and severity of disease.

Full Information

NCT ID

NCT00811486

First Posted

December 18, 2008

Last Updated

January 25, 2013

Sponsor

University of Colorado, Denver

1. Study Identification

Unique Protocol Identification Number

NCT00811486

Brief Title

Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure

Official Title

Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Withdrawn

Why Stopped

Only 1 patient recruited, and he withdrew

Study Start Date

January 2009 (undefined)

Primary Completion Date

July 2010 (Actual)

Study Completion Date

December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Secondary hyperaldosteronism and the non-osmotic release of arginine vasopressin (AVP) are the major factors in sodium and water retention in pulmonary arterial hypertension with right ventricular failure. Natriuretic doses of mineralocorticoid antagonist and aquaretic doses of V2 receptor antagonist will attenuate the sodium and water retention respectively, and be associated with clinical improvement.

Detailed Description

Much has been learned about the pathophysiological state that underlies the development of increased total body volume and edema in left ventricular failure. Very little, however, is known about the mechanism underlying systemic hypervolemia in patients with isolated right ventricular dysfunction. Patients with pulmonary arterial hypertension (PAH) represent a model of isolated right ventricular dysfunction in which these mechanisms may be elucidated. Aldosterone has now been shown to have many properties that are likely to be detrimental in congestive heart failure (CHF) and that are not shared by angiotensin II. Aldosterone blockade has been associated with improved mortality in patients with left ventricular failure, already receiving an angiotensin converting enzyme inhibitor. But its role in isolated right ventricular failure has not been elucidated. The plasma arginine vasopressin levels are disproportionately elevated for the degree of serum osmolarity in patients with heart failure and result in water retention and hyponatremia. Conivaptan, a vasopressin receptor antagonist, appears to reduce body weight and improve signs of left heart failure, though there is no study to evaluate its role in right ventricular failure with edema. This study will examine the role of spironolactone and conivaptan in patients with right ventricular failure and pathophysiology of sodium and water retention in these patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Right Heart Failure, Pulmonary Hypertension

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Usual care

Arm Type

No Intervention

Arm Description

Group II

Arm Title

Spironolactone and conivaptan

Arm Type

Experimental

Arm Description

Group I

Intervention Type

Drug

Intervention Name(s)

Spironolactone and conivaptan

Intervention Description

Tablet, 50 mg to 200 mg, daily, orally 20 mg intravenously one time over 30 minutes

Primary Outcome Measure Information:

Title

Cross sectional study

Description

Time Frame

18 months

Secondary Outcome Measure Information:

Title

Cross-sectional Study

Description

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 1. Patients with World Health Organization (WHO) group 1 pulmonary arterial hypertension [51], excluding patients with portal hypertension, meeting the following hemodynamic parameters: Mean pulmonary artery pressure (mPAP) >35 mmHg at rest, and Pulmonary capillary wedge pressure (PCWP) <15 mmHg, and Pulmonary vascular resistance (PVR) >1.5 wood units, and 2. Age 18 to 75 years 3. Right ventricular failure defined by right atrial pressure >7 mmHg along with either dilated right ventricle, or absence of inferior vena cava collapse or BNP >100 pg/ml 4. Patients of childbearing age must be practicing effective birth control. 5. Normal left ventricular function as assessed by echocardiogram, multiple gated acquisition (MUGA) cardiac scan, or invasive left ventriculography. Exclusion Criteria: 1. Group 2-5 pulmonary hypertension as defined by WHO. Pulmonary hypertension with left heart failure (as assessed by echocardiogram, multiple gated acquisition (MUGA) cardiac scan, or invasive left ventriculography). Pulmonary hypertension associated with lung disease and/or hypoxemia (e.g. chronic obstructive pulmonary disease, interstitial lung disease, sleep disordered breathing, chronic exposure to high altitude, alveolar hypoventilation syndrome. Pulmonary hypertension due to chronic thrombotic and/or embolic diseases Miscellaneous such as sarcoidosis, compression of pulmonary vessels by adenopathy, tumor 2. Systemic hypertension, defined as a systolic pressure >140 mmHg or a diastolic blood pressure >90 mmHg 3. Patients taking angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARBs) 4. Pregnancy 5. Chronic kidney disease (serum creatinine > 2.5mg/dl, proteinuria >500 mg/day, hematuria) 6. Cirrhosis or portal hypertension 7. Inability to provide informed consent. 8. Allergy to conivaptan or spironolactone. 9. Active malignancy 10. Patients receiving spironolactone 11. Enrollment in other interventional studies. 12. Patients on Highly Active Antiretroviral Therapy (HAART)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shweta Bansal, MD

Organizational Affiliation

UCHSC

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Colorado at Denver and Health Sciences Center General Clinical Research Center

City

Denver

State/Province

Colorado

ZIP/Postal Code

80262

Country

United States

12. IPD Sharing Statement

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Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure

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