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Sponsors and Collaborators: |
Competence Network for Congenital Heart Defects German Federal Ministry of Education and Research |
Information provided by: | Competence Network for Congenital Heart Defects |
ClinicalTrials.gov Identifier: | NCT00586794 |
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.
Condition | Intervention | Phase |
Pulmonary Arterial Hypertension (PAH) |
Drug: Sildenafil Drug: Placebo |
Phase IV |
Genetics Home Reference related topics: | pulmonary arterial hypertension |
MedlinePlus related topics: | High Blood Pressure |
ChemIDplus related topics: | Sildenafil citrate Sildenafil |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | Therapy of Pulmonary Arterial Hypertension (PAH) - Treatment With Sildenafil in Eisenmenger Patients |
Estimated Enrollment: | 80 |
Study Start Date: | December 2007 |
Estimated Study Completion Date: | December 2010 |
Estimated Primary Completion Date: | August 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
A: Active Comparator |
Drug: Sildenafil
3x per day 20 mg TID
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B: Placebo Comparator
from the 26th weeks on open-label, all patients were treated with Sildenafil
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Drug: Placebo
3x per day, 20 mg TID
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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, 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 2002).Good 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 (PAH)caused by congenital heart defects.
The hypotheses are:
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.
Ages Eligible for Study: | 14 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Non-specific:
Specific:
One of the following diagnoses:
non-corrected large congenital shunting defect at atrial, ventricular or arterial level:
Exclusion Criteria:
Non-specific:
Specific:
secondary impairment of organic function:
other sources of pulmonary blood flow which prohibit measurement of the blood flow into the lungs and therefore of the pulmonary vascular resistance:
Obstruction of pulmonary blood outflow:
Left heart diseases:
all contraindications against the study medication (see also "4.2.3 concomitant medication")
Prohibited concomitant medication:
Any medication listed below which has not been discontinued at least 30 days prior to screening. Specific pulmonary vasodilators during cardiac catheterization are allowed.
Instable medication (details: 4.2.5 prohibited concomitant medication):
Existing anti-pulmonary hypertensive medication (in any form) with:
Other medication with vascular action:
Medication that is not compatible with sildenafil or interferes with the metabolism:
Contact: Siegrun Mebus, MD | +49 89 1218 - 3010 | mebus@dhm.mhn.de |
Germany | |||||
Deutsches Herzzentrum Berlin, Abt. angeborener Herzfehler/Kinderkardiologie | Recruiting | ||||
Berlin, Germany, 13353 | |||||
Contact: Oliever Miera, MD +49-30-4593-2800 mira@dhzb.de | |||||
Principal Investigator: O. Miera, MD | |||||
Sub-Investigator: S. Eder | |||||
Sub-Investigator: B. Farahwaschy | |||||
Universitätsklinikum Erlangen, Kinderkardiologische Abteilung, Kinder- und Jugendklinik | Recruiting | ||||
Erlangen, Germany, 91054 | |||||
Contact: Prof. Sven Dittrich, Prof. Dr. med. 09131-8533750 sven.dittrich@kinder.imed.uni-erlangen.de | |||||
Principal Investigator: Prof. S. Dittrich, MD | |||||
Sub-Investigator: A. Koch, MD | |||||
Universitätsklinikum Charite, Campus Virchow-Klinikum, Otto-Heubner-Centrum für Kinder- und Jugendmedizin | Recruiting | ||||
Berlin, Germany, D-13353 | |||||
Contact: Lothar Schmitz, MD +49 30-450-566-873 lothar.schmitz@charite.de | |||||
Principal Investigator: Lothar Schmitz, MD | |||||
Sub-Investigator: K. Weiss, MD | |||||
Sub-Investigator: B. Opgen-Rhein, MD | |||||
Germany, Baden-Wuertemberg | |||||
Universitätsklinikum Freiburg, Klinik III Päd. Kardiologie | Recruiting | ||||
Freiburg, Baden-Wuertemberg, Germany, 79106 | |||||
Contact: Jochen Grohmann, MD +49 761 270 4317 jochen.grohmann@uniklinik-freiburg.de | |||||
Contact: Raoul Arnold, MD raoul.arnold@uniklinik-freiburg.de | |||||
Principal Investigator: J. Grohmann, MD | |||||
Sub-Investigator: R. Arnold, MD | |||||
Sub-Investigator: C. Rummer, MD | |||||
Medizinische Klinik und Poliklinik, Abteilung Innere Medizin III | Recruiting | ||||
Heidelberg, Baden-Wuertemberg, Germany, 69120 | |||||
Contact: F. J., Meyer +49 6221 5638 joachim_meyer@med.uni-heidelberg.de | |||||
Principal Investigator: F. J. Meyer, MD | |||||
Sub-Investigator: A. Filusch, MD | |||||
Sub-Investigator: F. Leuschner, MD | |||||
Sub-Investigator: W. Rottbauer, MD | |||||
Klinikum der Universität Heidelberg, Pädiatrische Kardiologie | Recruiting | ||||
Heidelberg, Baden-Wuertemberg, Germany, 69120 | |||||
Contact: M. Gorenflo, MD +49 6211 56 38365 matthias_gorenflo@med.uni-heidelberg.de | |||||
Principal Investigator: M. Gorenflo, MD | |||||
Sub-Investigator: D. Bucsenez, MD | |||||
Sub-Investigator: J. Eichhorn, MD | |||||
Sub-Investigator: M. Goetze, MD | |||||
Germany, Baden-Wuerttemberg | |||||
Universitätsklinikum Tübingen, Klinik für Kinderheilkunde und Jugendmedizin | Recruiting | ||||
Tübingen, Baden-Wuerttemberg, Germany, D-72076 | |||||
Contact: M. Hofbeck, Prof. +49 7071-298-4751 michael.hofbeck@med.uni-tuebingen.de | |||||
Principal Investigator: Prof. M. Hofbeck, MD | |||||
Sub-Investigator: C. Apitz, MD | |||||
Sub-Investigator: Prof. L. Sieverding, MD | |||||
Germany, Bavaria | |||||
Deutsches Herzzentrum München | Recruiting | ||||
Munich, Bavaria, Germany, D-80336 | |||||
Contact: John Hess, Prof. +49 89 1218 3011 hess@dhm.mhn.de | |||||
Principal Investigator: Prof. J. Hess, MD | |||||
Sub-Investigator: A. Hager, MD | |||||
Sub-Investigator: G. Balling, MD | |||||
Sub-Investigator: Prof. H. Kaemmerer, MD | |||||
Sub-Investigator: S. Mebus, MD | |||||
Ludwig-Maximilian-Universität München, Klinikum Großhadern, Abt. Kinderkardiologie und Intensivmedizin | Recruiting | ||||
München-Großhadern, Bavaria, Germany, D-81377 | |||||
Contact: Prof. H. Netz, MD +49 89 7095 3941 heinrich.netz@med.uni-muenchen.de | |||||
Principal Investigator: Prof. H. Netz, MD | |||||
Sub-Investigator: R. Dalla Pozza, MD | |||||
Sub-Investigator: S. Urschel, MD | |||||
Germany, Hesse | |||||
Universitätsklinikum Giessen and Marburg, Zentrum für Kinderheilkunde und Jugendmedizin | Recruiting | ||||
Giessen, Hesse, Germany, D-35385 | |||||
Contact: Rainer Zimmermann, MD 49 641 / 994 3400 rainer.zimmermann@paediat.med.uni-giessen.de | |||||
Principal Investigator: R. Zimmermann, MD | |||||
Sub-Investigator: Prof. J. Kreuder, MD | |||||
Germany, Lower Saxony | |||||
Elisabeth Kinderkrankenhaus, Zentrum für Kinder- und Jugendmedizin | Recruiting | ||||
Oldenburg, Lower Saxony, Germany, D-26133 | |||||
Contact: R. Motz, MD +49 441 403 2487 motz.reinald@klinikum-oldenburg.de | |||||
Principal Investigator: R. Motz, MD | |||||
Sub-Investigator: M. Schumacher, MD | |||||
Sub-Investigator: M. Viemann, MD | |||||
Sub-Investigator: K. Kronberg, MD | |||||
Medizinische Hochschule Hannover, Abt. für Kardiologie und Angiologie | Recruiting | ||||
Hannover, Lower Saxony, Germany, D-30625 | |||||
Contact: M. Westhoff-Bleck, MD +49 511 532 2568 westhoff-bleck.mechthild@mh-hannover.de | |||||
Principal Investigator: M. Westhoff-Bleck, MD | |||||
Sub-Investigator: G. P. Meyer, MD | |||||
Sub-Investigator: O. Tutarel, MD | |||||
Germany, North Rhine-Westphalia | |||||
Herz-und Diabeteszentrum NRW | Recruiting | ||||
Bad Oeynhausen, North Rhine-Westphalia, Germany, D-32545 | |||||
Contact: Nikolaus Haas, MD +49 5731 / 97 3620 nhaas@hdz-nrw.de | |||||
Principal Investigator: Nikolaus Haas, MD | |||||
Sub-Investigator: R. Schäffler, MD | |||||
Universitätsklinikum Schleswig-Holstein Campus Kiel | Recruiting | ||||
Kiel, North Rhine-Westphalia, Germany, D-24105 | |||||
Contact: Carsten Rickers, MD 49 431 / 597 1622 rickers@pedcard.uni-kiel.de | |||||
Principal Investigator: C. Rickers, MD | |||||
Sub-Investigator: I. Voges, MD | |||||
Evangelisches und Johanniter Klinikum Niederrhein gGmbH, Herzzentrum Duisburg | Recruiting | ||||
Duisburg, North Rhine-Westphalia, Germany, 47137 | |||||
Contact: Otto Krogmann, MD +49 230 451 3301 otto.krogman@ejk.de | |||||
Principal Investigator: O. Krogmann, MD | |||||
Sub-Investigator: K. Walter, MD | |||||
Germany, Saarland | |||||
Universitätsklinikum des Saarlandes | Recruiting | ||||
Homburg/Saar, Saarland, Germany, 66421 | |||||
Contact: Prof. Hashim Abdul-Khaliq, MD +49 6841 16 28305 abdul-khaliq@uniklinikum-saarland.de | |||||
Principal Investigator: Prof. Hashim Abdul-Khaliq, MD | |||||
Sub-Investigator: Axel Rentzsch, MD | |||||
Sub-Investigator: A. Lindinger, MD | |||||
Sub-Investigator: J. Olchvary, MD | |||||
Sub-Investigator: P. Schwarz, MD | |||||
Germany, Saxony | |||||
Universitätsklinikum der Martin-Luther-Universität Halle-Wittenberg | Recruiting | ||||
Halle / Saale, Saxony, Germany, 6120 | |||||
Contact: Prof. R. Grabitz, MD +49 345 557 2762 ralph.grabitz@medizin.uni-halle.de | |||||
Principal Investigator: Prof. R. Grabitz, MD | |||||
Sub-Investigator: H. Issa, MD | |||||
Sub-Investigator: K. Elsner |
Competence Network for Congenital Heart Defects |
German Federal Ministry of Education and Research |
Principal Investigator: | Siegrun Mebus, MD | German Heart Institute Munich, Competence Network for Congenital Heart Defects |
Study Chair: | Ingram Schulze-Neick, MD | Great Ormond Street Hospital for Sick Children,London |
(Competence Network for Congenital Heart Defects) 
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Responsible Party: | DHZB,German Heart Institute Munich, Competence Network for Congenital Heart Defects, ( Dr. Siegrun Mebus ) |
Study ID Numbers: | MP3.1 Sildenafil |
First Received: | December 21, 2007 |
Last Updated: | September 4, 2008 |
ClinicalTrials.gov Identifier: | NCT00586794 |
Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
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