Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure

• Status: Withdrawn
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Colorado, Denver
• Treatments: Conivaptan; Spironolactone

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)