Clinical Trial: Bosentan for Mild Pulmonary Vascular Disease in Asd Patients.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: BOsentan for Mild Pulmonary Vascular Disease in Asd Patients (the BOMPA Trial): a Double-blind, Randomized Controlled, Pilot Trial

Brief Summary:

Volume overload due to left-to-right shunting in patients with atrial septal defect type secundum causes pulmonary vascular disease over a long period of time. Pulmonary vascular resistance can be assessed non-invasively using bicycle stress echocardiography. By measuring cardiac output and pulmonary artery pressures at different stages of exercise, a pressure-output plot can be obtained. The slope of the pressure-output plot reflects pulmonary vascular resistance. In patients undergoing ASD repair after the age of 40 years, pulmonary vascular resistance was higher when compared to age-matched controls, indicating the presence of mild pulmonary vascular disease. Bosentan has been shown to decrease pulmonary vascular resistance.

The investigators hypothesize that in patients with an ASD type secundum, who underwent ASD repair after the age of 40 years, administration of bosentan decreases pulmonary vascular resistance as assessed by bicycle stress echocardiography.


Detailed Summary:

  1. INTRODUCTION AND RATIONALE

    1.1 MEDICAL BACKGROUND

    Atrial septal defect (ASD) represents approximately 10% of all congenital heart diseases and is the third most common form of congenital heart defect. The incidence of congenital heart disease in Belgium is 1%, with ASD accounting for 25% of the cases (Data from the database of congenital heart diseases UZ Leuven.) Characterized by a free communication between the left and the right atrium, it may take the form of an ostium secundum defect (in the region of the fossa ovalis); an ostium primum defect (in the lower part of the atrial septum and associated with mitral regurgitation) or a sinus venosus defect (in the upper atrial septum and associated with anomalous drainage of one or more pulmonary veins)

    Patients with atrial septal defect (ASD) initially present with a left-to-right shunt, which may cause elevated pulmonary artery pressures at rest and/or during exercise. However, this persistently elevated pulmonary blood-flow also causes progressive lesions of the pulmonary vasculature, as first described by Heath and Edwards. The earlier stages present with medial hypertrophy and/or intimal proliferation and are largely reversible after closure of the defect. Later stages, however, are irriversible: the origin of pulmonary arterial hypertension (PAH). Eventually, this volume and pressure overload of the right heart may lead to heart failure and/or arrhythmias. As PVR exceeds systemic resistance, the shunt is reversed (right-to-left shunt) leading to systemic arterial desaturation (and the related consequences: polyglobulia, hyperuricemia, decreased renal function and abnormal coagulation): the Eisenmenger syndrome (ES). When occlusive fibrotic le
    Sponsor: Universitaire Ziekenhuizen Leuven

    Current Primary Outcome: Pulmonary vascular resistance [ Time Frame: 16 weeks ]

    Pulmonary vascular resistance can be measured using bicycle stress echocardiography by estimating the slope of a pressure-flow plot using linear regression analysis.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Peak oxygen consumption [ Time Frame: 16 weeks ]
      The highest oxygen uptake available by bicycle ergometry despite further work rate increases and effort by the subject.
    • Right ventricular function [ Time Frame: 16 weeks ]
      Right ventricular function as assessed by echocardiography.
    • Liver function abnormalities [ Time Frame: 4, 8,12 and16 weeks ]
      An increase in ASAT and/or ALAT equal or more than 3 times the upper limit of normal.


    Original Secondary Outcome: Same as current

    Information By: Universitaire Ziekenhuizen Leuven

    Dates:
    Date Received: October 8, 2010
    Date Started: October 2010
    Date Completion:
    Last Updated: March 4, 2014
    Last Verified: March 2014