We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Spironolactone Combined With Captopril and Carvedilol for the Treatment of Pulmonary Arterial Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00240656
Recruitment Status : Completed
First Posted : October 18, 2005
Last Update Posted : June 30, 2008
Information provided by:
Hebei Medical University

Brief Summary:
The purpose of this study is to determine whether a larger dose of the aldosterone antagonist spironolactone combined with an ACE inhibitor (captopril) and a beta-blocker (carvedilol) is effective in reverse pulmonary artery remodeling in patients with pulmonary arterial hypertension (PAH)secondary to congenital heart disease

Condition or disease Intervention/treatment Phase
Hypertension, Pulmonary Drug: spironolactone captopril carvedilol Phase 1

Detailed Description:
The pathogenesis of PAH involves multiple mechanisms. However, three common factors are thought to cause the increased pulmonary vascular resistance that characterizes this devastating disease: vasoconstriction, pulmonary vascular proliferation and remodeling, and thrombosis in situ. Advances in our knowledge of the molecular mechanisms involved in PAH suggest that endothelial dysfunction with chronic impaired production of vasoactive mediators plays a key role. Reduced production of vasoactive mediators, such as nitric oxide (NO) and prostacyclin, along with prolonged overexpression of vasoconstrictors such as endothelin-1 (ET-1), not only affect vascular tone but also promote vascular remodeling. Thus, these substances represent logical pharmacological targets. Animal studies showed ET-1 could stimulate aldosterone secretion in different species, both in vivo and in vitro. This stimulation involves the ET-B alone and both ET-A and ET-B receptor subtypes in rats and humans. Animal studies also showed spironolactone combined with ACE inhibitor could normalize blood pressure, prevents upregulation of vascular ET-1, restore nitric oxide (NO)-mediated endothelial dysfunction. Beta-blockers have ability to reduce dp/dt in pulmonary artery, as well as left ventricle, thus prevent further damage to the dysfunctional endothelium. Furthermore, we observed from our practice that the aforementioned therapy could lower pulmonary artery pressure in patents with pulmonary hypertension secondary to left ventricular dysfunction. Thus, we hypothesize spironolactone combined with ACE inhibitor and beta-blocker has the ability to reverse remodeling of pulmonary artery in PAH patients.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Official Title: Spironolactone Combined With Captopril and Carvedilol for the Treatment of Patients With Pulmonary Arterial Hypertension Associated With Congenital Heart Disease-Focus on Pulmonary Artery Remodeling
Study Start Date : October 2005
Study Completion Date : May 2006

Primary Outcome Measures :
  1. Dyspnoea score
  2. Exercise capacity (six-minute walk)
  3. NYHA/WHO functional class
  4. Change of acropachy
  5. Blood gas test
  6. Pulmonary artery pressure (measured by echocardiogram or catheter)

Secondary Outcome Measures :
  1. Other echocardiographic changes:
  2. Systolic pulmonary arterial pressure
  3. Change of right to left shunt expressed by time-velocity integral (TVI) from the defect
  4. Change of left to right shunt expressed by TVI from the defect
  5. Right ventricular (RV) acceleration time (ms)
  6. RV ejection time (ms)
  7. Ratio of RV ejection time/RV acceleration time
  8. Pulmonary arterial valve TVI
  9. Change of diameters of both left and right ventricles
  10. Change of diameters of both left and right atrium
  11. Doppler mitral valve (MV) TVI
  12. Blood gas test

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   up to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • A mean pulmonary artery pressure higher than 25 mm Hg or, when estimated by echocardiography, pulmonary artery pressure more than half the systemic artery pressure
  • Congenital systemic-to-pulmonary shunts

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): NCT00240656

Layout table for location information
China, Hebei
The First Hospital of Hebei Medical University
Shijiazhuang, Hebei, China, 050031
Sponsors and Collaborators
Hebei Medical University
Layout table for investigator information
Study Chair: Kunshen Liu, M.D. The First Hospital of Hebei Medical University
Layout table for additonal information
ClinicalTrials.gov Identifier: NCT00240656    
Other Study ID Numbers: 0510-A
First Posted: October 18, 2005    Key Record Dates
Last Update Posted: June 30, 2008
Last Verified: October 2005
Keywords provided by Hebei Medical University:
aldosterone antagonists, spironolactone, captopril carvedilol
Additional relevant MeSH terms:
Layout table for MeSH terms
Pulmonary Arterial Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Protective Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists