Clinical Trials Logo

Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT00811486
Other study ID # 07-1022
Secondary ID
Status Withdrawn
Phase N/A
First received December 18, 2008
Last updated January 25, 2013
Start date January 2009
Est. completion date December 2010

Study information

Verified date January 2013
Source University of Colorado, Denver
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date December 2010
Est. primary completion date July 2010
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 75 Years
Eligibility 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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
Spironolactone and conivaptan
Tablet, 50 mg to 200 mg, daily, orally 20 mg intravenously one time over 30 minutes

Locations

Country Name City State
United States University of Colorado at Denver and Health Sciences Center General Clinical Research Center Denver Colorado

Sponsors (1)

Lead Sponsor Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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) 18 months No
Secondary 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. 18 months No
See also
  Status Clinical Trial Phase
Withdrawn NCT01950585 - Hydroxyurea in Pulmonary Arterial Hypertension Early Phase 1
Completed NCT00527163 - Role of Nitric Oxide in Malaria
Completed NCT03649932 - Enteral L Citrulline Supplementation in Preterm Infants - Safety, Efficacy and Dosing Phase 1
Recruiting NCT04554160 - Arrhythmias in Pulmonary Hypertension Assessed by Continuous Long-term Cardiac Monitoring
Enrolling by invitation NCT03683186 - A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension Phase 3
Completed NCT01894035 - Non-interventional Multi-center Study on Patients Under Routine Treatment of Pulmonary Arterial Hypertension (PAH) With Inhaled Iloprost Using I-Neb as a Device for Inhalation
Not yet recruiting NCT04083729 - Persistent Pulmonary Hypertension After Percutaneous Mitral Commissurotomy N/A
Terminated NCT02243111 - Detecting Pulmonary Arterial Hypertension (PAH) in Patients With Systemic Sclerosis (SSc) by Ultrasound N/A
Completed NCT02821156 - Study on the Use of Inhaled NO (iNO) N/A
Completed NCT02216279 - Phase-II Study of the Use of PulmoBind for Molecular Imaging of Pulmonary Hypertension Phase 2
Terminated NCT02246348 - Evaluating Lung Doppler Signals in Patients With Systemic Sclerosis (SSc) N/A
Recruiting NCT01913847 - Safety and Efficacy Study of HGP1207 in Patients With Pulmonary Hypertension Phase 3
Completed NCT06240871 - Contrast Enhanced PA Pressure Measurements
Completed NCT01615484 - Ex-vivo Perfusion and Ventilation of Lungs Recovered From Non-Heart-Beating Donors to Assess Transplant Suitability N/A
Completed NCT02377934 - Evaluation of Radiation Induced Pulmonary Hypertension Using MRI in Stage III NSCLC Patients Treated With Chemoradiotherapy. A Pilot Study
Recruiting NCT01091012 - Effectiveness of the Vasodilator Test With Revatio, Made in Patients With Acute Pulmonary Hypertension Phase 3
Completed NCT01463514 - Noninvasive Determination of Cerebral Tissue Oxygenation in Pulmonary Hypertension N/A
Completed NCT02275793 - The Regulation of Pulmonary Vascular Resistance in Patients With Heart Failure
Completed NCT00739375 - The Effect of Blood Flow in the Maturing Arteriovenous Access for Hemodialysis on the Development of Pulmonary Hypertension. Phase 1
Completed NCT01484899 - Smoking: a Risk Factor for Pulmonary Arterial Hypertension? N/A