Clinical Trial: Bosentan in Treatment of Pulmonary Arterial Hypertension

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

Official Title: Therapy of Pulmonary Arterial Hypertension (PAH) With Bosentan in Patients With Eisenmenger Syndrome

Brief Summary: Eisenmenger's syndrome presents as a severe clinical picture of polymorbidity that constitutes a great burden at the individual as well as the familial and social level. The combination of critically increased pulmonary vascular resistance, progressive pressure load of the right ventricle and disturbance of pulmonary gas exchange result in long-term polymorbidity. The objective of this study is to look into the effects of medium-term pulmonary pressure-lowering treatment with oral bosentan in patients with congenital heart defects and clinically relevant pulmonary arterial hypertension (PAH), taking advantage of extensive diagnostic procedures.

Detailed Summary:

Eisenmenger's syndrome presents as a severe clinical picture of polymorbidity that constitutes a great burden at the individual as well as the familial and social level. The combination of critically increased pulmonary vascular resistance, progressive pressure load of the right ventricle and disturbance of pulmonary gas exchange result in long-term polymorbidity. While the patient's ability to care for him-/ herself gets lost over time, the financial burden due to the need for medical consultations and hospital stays increases. This is distressing to both the patient and the family. Usually, death results from cardiac decompensation in the presence of gradually increasing pulmonary vascular resistance and hypoxic lesion of organs including the myocardium (Hopkins, AJC 2002).

With a better understanding of the pathophysiology underlying pulmonary hypertension, novel therapeutic approaches have been developed during the past few years. These include a) inhibition of the NO-cGMP-degrading type 5 phosphodiesterase (PDE-5) and b) antagonising the endothelin system (Krum, Curr Opin Investig Drugs 2003). The goal is a dilatation of the abnormally constricted pulmonary arterial vessels by relaxation of the vascular smooth muscle cells with a reversal of pulmonary vascular remodelling (Ghofrani, Pneumologie 2002).

Specific drugs affecting pulmonary vascular resistance have been studied. Intravenous prostacyclin has major disadvantages: high cost, tachyphylaxis, risk of infection and rebound hypertension upon discontinuation. Inhalative pulmonary vasodilators, in particular iloprost, may be effective in primary pulmonary hypertension (Olschewski, Ann Int Med 1996; Hoeper, Pneumologie 2001), but administration is time-consuming, and due to its mode of application its effects are intermittent, lasting only about 75 minutes (Hoeper, J
Sponsor: Competence Network for Congenital Heart Defects

Current Primary Outcome:

  • maximal exercise tolerance (walking distance in the 6-minute walking test)
  • peripheral oxygen saturation (SatO2)
  • pulmonary-systemic ratio of arterial resistance (Rp:Rs)


Original Primary Outcome:

  • · maximal exercise tolerance (walking distance in the 6-minute walking test)
  • · peripheral oxygen saturation (SatO2)
  • · pulmonary-systemic ratio of arterial resistance (Rp:Rs)


Current Secondary Outcome:

  • NYHA class
  • increase in pulmonary reagibility by bosentan therapy
  • normalisation of vasoactive mediators by bosentan therapy


Original Secondary Outcome:

  • · NYHA class
  • · increase in pulmonary reagibility by bosentan therapy
  • · normalisation of vasoactive mediators by bosentan therapy


Information By: Competence Network for Congenital Heart Defects

Dates:
Date Received: December 15, 2005
Date Started: August 2004
Date Completion:
Last Updated: May 6, 2008
Last Verified: May 2008