Ignite Creation Date:
2024-05-05 @ 6:58 PM
Last Modification Date:
2024-10-26 @ 9:40 AM
Study NCT ID:
NCT00586794
Status:
TERMINATED
Last Update Posted:
2012-06-06
First Post:
2007-12-21
Brief Title:
Therapy of Pulmonary Arterial Hypertension PAH - Treatment With Sildenafil in Eisenmenger Patients
Sponsor:
Competence Network for Congenital Heart Defects
Organization:
Competence Network for Congenital Heart Defects
Study Overview
Official Title:
Therapy of Pulmonary Arterial Hypertension PAH - Treatment With Sildenafil in Eisenmenger Patients
Status:
TERMINATED
Status Verified Date:
2010-10
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 provide evidence of improvement of patients exercise tolerance as well as general conditions by treatment with oral sildenafil as a specific pulmonary vasodilator
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
Sildenafil Revatio an inhibitor of the phosphodiesterase 5 PDE-5 was used in many individual cases Abrams Schulze-Neick et al Heart 2000 some acute studies and two long-term studies in humans to reduce the pulmonary vessel resistance Significant effects on reduction of the pulmonary vessel resistance were demonstrated for the combination with an inhalational prostanoid Ghofrani et al Ann Int Med 2002Good long-term tolerability and effectiveness over a period of two year were demonstrated by this working group
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 The data obtained are supposed to contribute to the development of guidelines for the treatment of Pulmonary Arterial Hypertension PAHcaused by congenital heart defects
The hypotheses are
1 Sildenafil heales specific pulmonary vascular damage which occurs by hypercirculation as quick-acting inhibiting vasoconstriction
2 Through this there will be a reduction of pulmonary vessel resistance and a normalization of pulmonary reagibility in patients with Eisenmenger syndrome
3 Pulmonary blood circulation and so systemic arterial oxygen delivery will increase
4 The patient benefits from this by improving his exercise tolerance as well as general and clinical condition
These hypotheses will be tested by comparing findings of the following examinations before during and after the 52 or 78-week treatment with sildenafil clinical examination Electrocardiogram ECG echocardiography ergospirometry Magnetic Resonance Imaging MRI cardiac catheterization with pulmonary artery manometry and laboratory tests
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
Sildenafil Revatio an inhibitor of the phosphodiesterase 5 PDE-5 was used in many individual cases Abrams Schulze-Neick et al Heart 2000 some acute studies and two long-term studies in humans to reduce the pulmonary vessel resistance Significant effects on reduction of the pulmonary vessel resistance were demonstrated for the combination with an inhalational prostanoid Ghofrani et al Ann Int Med 2002Good long-term tolerability and effectiveness over a period of two year were demonstrated by this working group
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 The data obtained are supposed to contribute to the development of guidelines for the treatment of Pulmonary Arterial Hypertension PAHcaused by congenital heart defects
The hypotheses are
1 Sildenafil heales specific pulmonary vascular damage which occurs by hypercirculation as quick-acting inhibiting vasoconstriction
2 Through this there will be a reduction of pulmonary vessel resistance and a normalization of pulmonary reagibility in patients with Eisenmenger syndrome
3 Pulmonary blood circulation and so systemic arterial oxygen delivery will increase
4 The patient benefits from this by improving his exercise tolerance as well as general and clinical condition
These hypotheses will be tested by comparing findings of the following examinations before during and after the 52 or 78-week treatment with sildenafil clinical examination Electrocardiogram ECG echocardiography ergospirometry Magnetic Resonance Imaging MRI cardiac catheterization with pulmonary artery manometry and laboratory tests
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