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Sponsored by: |
Hebei Medical University |
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Information provided by: | Hebei Medical University |
ClinicalTrials.gov Identifier: | NCT00240656 |
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 I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
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 |
Estimated Study Completion Date: | May 2006 |
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:
China, Hebei Province | |
The First Hospital of Hebei Medical University | |
Shijiazhuang, Hebei Province, China, 050031 |
Study Chair: | Kunshen Liu, M.D. | The First Hospital of Hebei Medical University |
Study ID Numbers: | 0510-A |
Study First Received: | October 17, 2005 |
Last Updated: | June 27, 2008 |
ClinicalTrials.gov Identifier: | NCT00240656 History of Changes |
Health Authority: | China: State Food and Drug Administration |
aldosterone antagonists, spironolactone, captopril carvedilol |
Neurotransmitter Agents Vasodilator Agents Adrenergic Agents Hormone Antagonists Diuretics Hormones, Hormone Substitutes, and Hormone Antagonists Hormones Respiratory Tract Diseases Idiopathic Pulmonary Hypertension Angiotensin-Converting Enzyme Inhibitors Adrenergic beta-Antagonists Carvedilol Captopril |
Heart Diseases Vascular Diseases Cardiovascular Agents Adrenergic alpha-Antagonists Antihypertensive Agents Protease Inhibitors Spironolactone Aldosterone Antagonists Hypertension, Pulmonary Lung Diseases Adrenergic Antagonists Hypertension |
Vasodilator Agents Neurotransmitter Agents Adrenergic Agents Molecular Mechanisms of Pharmacological Action Hormone Antagonists Diuretics Physiological Effects of Drugs Hormones, Hormone Substitutes, and Hormone Antagonists Respiratory Tract Diseases Therapeutic Uses Angiotensin-Converting Enzyme Inhibitors Adrenergic beta-Antagonists Cardiovascular Diseases Carvedilol Captopril |
Vascular Diseases Enzyme Inhibitors Adrenergic alpha-Antagonists Cardiovascular Agents Antihypertensive Agents Pharmacologic Actions Protease Inhibitors Spironolactone Aldosterone Antagonists Hypertension, Pulmonary Natriuretic Agents Lung Diseases Adrenergic Antagonists Hypertension |