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

• ClinicalTrials.gov Identifier: NCT00240656
• Recruitment Status: Completed
• First Posted: October 18, 2005
• Last Update Posted: June 30, 2008
• Sponsor: Hebei Medical University
• Information provided by: Hebei Medical University

Study Description

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.

Study Design

• 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

Arms and Interventions

Outcome Measures

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

China, Hebei

The First Hospital of Hebei Medical University

Shijiazhuang, Hebei, China, 050031

Sponsors and Collaborators

Hebei Medical University

Investigators

• Study Chair: Kunshen Liu, M.D.; The First Hospital of Hebei Medical University

More Information

Additional Information:

Related Info 

• ClinicalTrials.gov Identifier: NCT00240656
• Other Study ID Numbers: 0510-A
• First Posted: October 18, 2005
• 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:

Hypertension, Pulmonary; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Carvedilol; Captopril; Spironolactone; Mineralocorticoid Receptor Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Antioxidants; Protective Agents; Calcium Channel Blockers; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Vasodilator Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists