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

This study has been completed.
Information provided by:
Hebei Medical University
ClinicalTrials.gov Identifier:
First received: October 17, 2005
Last updated: June 27, 2008
Last verified: October 2005
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 Intervention Phase
Hypertension, Pulmonary
Drug: spironolactone captopril carvedilol
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Hebei Medical University:

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

Secondary Outcome Measures:
  • Other echocardiographic changes:
  • Systolic pulmonary arterial pressure
  • Change of right to left shunt expressed by time-velocity integral (TVI) from the defect
  • Change of left to right shunt expressed by TVI from the defect
  • Right ventricular (RV) acceleration time (ms)
  • RV ejection time (ms)
  • Ratio of RV ejection time/RV acceleration time
  • Pulmonary arterial valve TVI
  • Change of diameters of both left and right ventricles
  • Change of diameters of both left and right atrium
  • Doppler mitral valve (MV) TVI
  • Blood gas test

Study Start Date: October 2005
Estimated Study Completion Date: May 2006
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.

Ages Eligible for Study:   up to 80 Years
Genders Eligible for Study:   Both
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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00240656

China, Hebei
The First Hospital of Hebei Medical University
Shijiazhuang, Hebei, China, 050031
Sponsors and Collaborators
Hebei Medical University
Study Chair: Kunshen Liu, M.D. Hebei Medical University First Hospital
  More Information

Additional Information:
ClinicalTrials.gov Identifier: NCT00240656     History of Changes
Other Study ID Numbers: 0510-A 
Study First Received: October 17, 2005
Last Updated: June 27, 2008
Health Authority: China: Food and Drug Administration

Keywords provided by Hebei Medical University:
aldosterone antagonists, spironolactone, captopril carvedilol

Additional relevant MeSH terms:
Familial Primary Pulmonary Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Adrenergic Agents
Adrenergic Antagonists
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic beta-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Diuretics, Potassium Sparing
Enzyme Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Protease Inhibitors
Vasodilator Agents

ClinicalTrials.gov processed this record on May 30, 2016