Clinical Trial: Therapy of Pulmonary Arterial Hypertension (PAH) - Treatment With Sildenafil in Eisenmenger Patients

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Therapy of Pulmonary Arterial Hypertension (PAH) - Treatment With Sildenafil in Eisenmenger Patients

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 provide evidence of improvement of patients exercise tolerance as well as general conditions by treatment with oral sildenafil as a specific pulmonary vasodilator.

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: To determine the distance of walking, which is performed during a 6- min walking test; oxygen saturation and relation of resistance Rp : Rs during the examination with "Herzkatheter", described as the difference between visit 1 (baseline) and visit 4 [ Time Frame: visit 1 and visit 4 (after 26 weeks) ]

Original Primary Outcome: • To determine the distance of walking, which is performed during a 6- min walking test; oxygen saturation and relation of resistance Rp : Rs during the examination with "Herzkatheter", described as the difference between visit 1 (baseline) and visit 4 [ Time Frame: visit 1 and visit 4 (after 26 weeks) ]

Current Secondary Outcome:

  • To provide normalization of pulmonary vascular function (reagibility and vasoactive mediators) in dependence on duration of the therapy [ Time Frame: 78 weeks ]
  • Parameters of MRI and Echo-diagnostic [ Time Frame: 78 weeks ]
  • Quality of life (SF-36) [ Time Frame: 78 weeks ]
  • Safety and tolerance of the treatment [ Time Frame: 78 weeks ]


Original Secondary Outcome: • To provide normalization of pulmonary vascular function (reagibility and vasoactive mediators) in dependence on duration of the therapy • Parameters of MRI and Echo-diagnostic • Quality of life (SF-36) • Safety and tolerance of the treatment [ Time Frame: 78 weeks ]

Information By: Competence Network for Congenital Heart Defects

Dates:
Date Received: December 21, 2007
Date Started: December 2007
Date Completion:
Last Updated: June 5, 2012
Last Verified: October 2010