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Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure

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ClinicalTrials.gov Identifier: NCT00811486
Recruitment Status : Withdrawn (Only 1 patient recruited, and he withdrew)
First Posted : December 19, 2008
Last Update Posted : January 28, 2013
Sponsor:
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment
Right Heart Failure Pulmonary Hypertension Drug: Spironolactone and conivaptan

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure
Study Start Date : January 2009
Primary Completion Date : July 2010
Study Completion Date : December 2010


Arms and Interventions

Arm Intervention/treatment
No Intervention: Usual care
Group II
Experimental: Spironolactone and conivaptan
Group I
Drug: Spironolactone and conivaptan
Tablet, 50 mg to 200 mg, daily, orally 20 mg intravenously one time over 30 minutes


Outcome Measures

Primary Outcome Measures :
  1. Cross sectional study [ Time Frame: 18 months ]
    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 :
  1. Cross-sectional Study [ Time Frame: 18 months ]
    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.


Eligibility Criteria

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00811486


Locations
United States, Colorado
University of Colorado at Denver and Health Sciences Center General Clinical Research Center
Denver, Colorado, United States, 80262
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Shweta Bansal, MD UCHSC
More Information

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00811486     History of Changes
Other Study ID Numbers: 07-1022
First Posted: December 19, 2008    Key Record Dates
Last Update Posted: January 28, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Hypertension
Heart Failure
Hypertension, Pulmonary
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Lung Diseases
Respiratory Tract Diseases
Spironolactone
Conivaptan
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action