Ignite Creation Date:
2024-05-05 @ 12:09 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00266162
Status:
COMPLETED
Last Update Posted:
2008-05-07
First Post:
2005-12-15
Brief Title:
Bosentan in Treatment of Pulmonary Arterial Hypertension
Sponsor:
Competence Network for Congenital Heart Defects
Organization:
Competence Network for Congenital Heart Defects
Study Overview
Official Title:
Therapy of Pulmonary Arterial Hypertension PAH With Bosentan in Patients With Eisenmenger Syndrome
Status:
COMPLETED
Status Verified Date:
2008-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Eisenmengers 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 Description:
Eisenmengers 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 patients 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 JACC 2000 Considering this oral treatments appear preferable because of easy administration and hence better patient compliance
Bosentan Tracleer is a non-selective endothelin receptor antagonist with dual binding ETA and ETB and complete blocking of endothelin-1 It is the first drug of this class that was approved for the lowering of pulmonary vascular resistance Significant effects on haemodynamics and exercise tolerance were demonstrated for both monotherapy Galie J Am Coll Cardiol 2003 Rubin N Engl J Med 2002 and add-on treatment with inhalational and parenteral prostanoids Hoeper Eur Respir J 2003 In children with at least 10 kg body weight bosentan significantly improved pulomary haemodynamics while pharmacokinetics was found to be comparable to that in adults Bars Clin Pharmacol Ther 2003 Good long-term tolerability and effectiveness over a period of one year were demonstrated Sitbon Chest 2003 Moreover in animal models of increased pulmonary blood flow activation of the endothelin system was absent under bosentan treatment and both haemodynamic and morphological changes were prevented Available data suggest that the effects of bosentan are not limited to primary pulmonary hypertension Further studies are required to prove its effectiveness in pulmonary hypertension of various aetiologies
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 The data obtained are supposed to contribute to the development of guidelines for the treatment of PAH caused by congenital heart defects The data will be further evaluated in terms of health economics network subproject Health Economics project manager Prof Dr med Karl W Lauterbach
The hypotheses are
1 Bosentan specifically improves the pulomonary vascular damage caused by hypercirculation As an immediate effect it blocks vasoconstriction and on the long run it reverts pulmonary vascular remodelling
2 In patients with Eisenmengers syndrome this results in a decrease in pulmonary vascular resistance and a normalization of pulmonary vascular responsiveness
3 This is followed by an increase in lung perfusion and systemic oxygen supply
4 The patient benefits from an improvement in hisher clinical condition and exercise tolerance
These hypotheses will be tested by comparing findings of the following examinations before and immediately after the 24-week treatment with bosentan clinical examination ECG echocardiography CPX MRT cardiac catheterization with pulmonary artery manometry and laboratory tests As a secondary objective the degree of concordance of findings of different invasive and non-invasive examinations and diagnostic procedures will be investigated
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 JACC 2000 Considering this oral treatments appear preferable because of easy administration and hence better patient compliance
Bosentan Tracleer is a non-selective endothelin receptor antagonist with dual binding ETA and ETB and complete blocking of endothelin-1 It is the first drug of this class that was approved for the lowering of pulmonary vascular resistance Significant effects on haemodynamics and exercise tolerance were demonstrated for both monotherapy Galie J Am Coll Cardiol 2003 Rubin N Engl J Med 2002 and add-on treatment with inhalational and parenteral prostanoids Hoeper Eur Respir J 2003 In children with at least 10 kg body weight bosentan significantly improved pulomary haemodynamics while pharmacokinetics was found to be comparable to that in adults Bars Clin Pharmacol Ther 2003 Good long-term tolerability and effectiveness over a period of one year were demonstrated Sitbon Chest 2003 Moreover in animal models of increased pulmonary blood flow activation of the endothelin system was absent under bosentan treatment and both haemodynamic and morphological changes were prevented Available data suggest that the effects of bosentan are not limited to primary pulmonary hypertension Further studies are required to prove its effectiveness in pulmonary hypertension of various aetiologies
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 The data obtained are supposed to contribute to the development of guidelines for the treatment of PAH caused by congenital heart defects The data will be further evaluated in terms of health economics network subproject Health Economics project manager Prof Dr med Karl W Lauterbach
The hypotheses are
1 Bosentan specifically improves the pulomonary vascular damage caused by hypercirculation As an immediate effect it blocks vasoconstriction and on the long run it reverts pulmonary vascular remodelling
2 In patients with Eisenmengers syndrome this results in a decrease in pulmonary vascular resistance and a normalization of pulmonary vascular responsiveness
3 This is followed by an increase in lung perfusion and systemic oxygen supply
4 The patient benefits from an improvement in hisher clinical condition and exercise tolerance
These hypotheses will be tested by comparing findings of the following examinations before and immediately after the 24-week treatment with bosentan clinical examination ECG echocardiography CPX MRT cardiac catheterization with pulmonary artery manometry and laboratory tests As a secondary objective the degree of concordance of findings of different invasive and non-invasive examinations and diagnostic procedures will be investigated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01G10210 | None | None | None |