Bosentan in Treatment of Pulmonary Arterial Hypertension

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Eisenmenger Syndrome	Drug: Bosentan administration	Phase 4

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Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	60 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Therapy of Pulmonary Arterial Hypertension (PAH) With Bosentan in Patients With Eisenmenger Syndrome
Study Start Date :	August 2004
Actual Primary Completion Date :	February 2008
Actual Study Completion Date :	February 2008

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

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

Secondary Outcome Measures :

1. NYHA class
2. increase in pulmonary reagibility by bosentan therapy
3. normalisation of vasoactive mediators by bosentan therapy

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Non-specific:

  • Written informed consent obtained

• Specific:

  • Age at least 18 years
  • Presence of cyanosis with < 93 % arterial oxygen saturation (measured by transcutaneous pulse oximetry)
  • Clinical indication for the invasive diagnostic procedures planned for the study is given; this is evaluated on the basis of observation before, during and after medicinal treatment)
  • Presence of PAH as diagnosed by invasive methods with Rp:Rs > 0.75 measured at rest, before testing of pulmonary vasodilatory reserve

  • One of the following diagnoses:

    • non-corrected large congenital shunting defect at atrial, ventricular or arterial level: PAPVD, ASD, SVD, VSD, AVSD, TAC, APW, PDA, or a combination of these.
    • Surgically corrected shunting defect (diagnoses as above) with significant residual defect
    • Other diagnoses with univentricular physiology/haemodynamics.

Exclusion Criteria:

• Non-specific:

  • pregnancy or lactation
  • women of child-bearing age who are sexually active without practising reliable methods of contraception
  • any disease or impairment that, in the opinion of the investigator, excludes a subject from participation
  • substance abuse (alcohol, medicines, drugs)
  • other medical, psychological or social circumstances that would adversely affect a patient's ability to participate adequately in the study or increase the risk to the patient or others in the case of participation.
  • insufficient compliance
  • subjects in whom MRI cannot be performed (contrast medium allergy, claustrophobia, cardiac pacemaker)
  • subjects who are not able to perform CPX

• Specific:

  • pulmonary hypertension of any aetiology other than those specified in the inclusion criteria
  • subjects with known intolerance of NO or iloprost or their constituents
  • acute decompensated heart failure within 7 days before the invasive procedure
  • haemodynamic instability that would increase the risk of pulmonary arterial reactivity testing
  • arterial hypotension
  • anaemia (Hb < 10 g/dl)
  • decompensated symptomatic polycythaemia
  • thrombocytopenia (< 50,000/μl)
  • secondary impairment of organic (renal, hepatic) function
  • other sources of pulmonary blood flow which render the measurement of the blood flow to the lungs and pulmonary vascular resistance impossible
  • obstruction of pulmonary blood outflow
  • left ventricular diseases
  • significant valvular diseases other than tricuspid or pulmonary regurgitation
  • pericardial constriction
  • history of stroke, myocardial infarction or life-threatening arrhythmia within 6 months before screening
  • bronchopulmonary dysplasia or other chronic lung diseases
  • history of significant pulmonary embolism
  • other relevant diseases (e.g. HIV infection)
  • trisomy 21
  • Prohibited concomitant medication: Any medication listed below which has not been discontinued at least 30 days prior to screening.
  • Unspecified or other significant medication (e.g. medication for diabetes or immunosuppression)
  • Unstable medication, recent changes in dosage regimen
  • Drugs to treat pulmonary hypertension (endothelin receptor antagonists, PDE-5 antagonists, prostanoids. (Specific pulmonary vasodilators during cardiac catheterisation are allowed.)
  • Other medication with vascular action
  • Medication that is not compatible with bosentan or that interferes with its metabolism (inhibitors of CYP2C9 or CYP3A4) or that, in the investigator's opinion, may interfere with bosentan treatment

Contacts and Locations

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Locations

Germany
Kinderkardiologie Universitätsklinikum Freiburg
Freiburg, Baden-Wuerttemberg, Germany, D-79106
Deutsches Herzzentrum Muenchen
Munich, Bavaria, Germany, D-80636
Universitätsklinikum Giessen and Marburg
Giessen, Hesse, Germany, D-35385
Herz-und Diabeteszentrum NRW
Bad Oeynhausen, North Rhine-Westphalia, Germany, D-32545
Universitätsklinikum Schleswig-Holstein Campus Kiel
Kiel, North Rhine-Westphalia, Germany, D-24105
Universitätsklinikum des Saarlandes
Homburg, Saarland, Germany, D-66421
Universitätsklinikum der Martin-Luther-Universität Halle-Wittenberg
Halle, Saxony-Anhalt, Germany, D-06097
Deutsches Herzzentrum Berlin
Berlin, Germany, D-13353

Sponsors and Collaborators

Competence Network for Congenital Heart Defects

German Federal Ministry of Education and Research

Actelion

Investigators

Principal Investigator:	Ingram Schulze-Neick, MD	German Heart Institute

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

ClinicalTrials.gov Identifier:	NCT00266162 History of Changes
Other Study ID Numbers:	MP 3.2; 01G10210
First Posted:	December 16, 2005
Last Update Posted:	May 7, 2008
Last Verified:	May 2008

Keywords provided by Competence Network for Congenital Heart Defects:

Heart Defects, Congenital; Eisenmenger Complex; Hypertension, Pulmonary	Pulmonary Heart Disease; Pulmonary Circulation; Vascular Resistance

Additional relevant MeSH terms:

Syndrome; Hypertension; Familial Primary Pulmonary Hypertension; Eisenmenger Complex; Disease; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases	Respiratory Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Diseases; Congenital Abnormalities; Bosentan; Antihypertensive Agents; Endothelin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action