Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure
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.
Right Heart Failure
Drug: Spironolactone and conivaptan
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure|
- Cross sectional study [ Time Frame: 18 months ] [ Designated as safety issue: No ]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)
- Cross-sectional Study [ Time Frame: 18 months ] [ Designated as safety issue: No ]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.
|Study Start Date:||January 2009|
|Study Completion Date:||December 2010|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
No Intervention: Usual care
Experimental: Spironolactone and conivaptan
Drug: Spironolactone and conivaptan
Tablet, 50 mg to 200 mg, daily, orally 20 mg intravenously one time over 30 minutes
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00811486
|United States, Colorado|
|University of Colorado at Denver and Health Sciences Center General Clinical Research Center|
|Denver, Colorado, United States, 80262|
|Principal Investigator:||Shweta Bansal, MD||UCHSC|