Effects of Tracleer (Bosentan) on Pulmonary Arterial Hypertension Related to Eisenmenger Physiology

This study has been completed.
Sponsor:
Information provided by:
Actelion
ClinicalTrials.gov Identifier:
NCT00317486
First received: April 21, 2006
Last updated: February 11, 2010
Last verified: February 2010
  Purpose

This study evaluates the effects of bosentan on oxygen saturation, hemodynamics and exercise capacity in patients with pulmonary arterial hypertension related to Eisenmenger physiology. Patients receive bosentan or placebo for 16 weeks.


Condition Intervention Phase
Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
Drug: bosentan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Tracleer (Bosentan) on Oxygen Saturation and Cardiac Hemodynamics in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Change from baseline to Week 16 in oxygen saturation at rest with room air
  • Change from baseline to Week 16 in indexed pulmonary vascular resistance

Secondary Outcome Measures:
  • Changes from baseline to Week 16 in cardiac hemodynamics

Enrollment: 54
Study Start Date: September 2003
Study Completion Date: April 2005
Primary Completion Date: April 2005 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients at least 12 years with a body weight at least 40 kg (inclusive) and with a functional class III (1998 WHO classification).
  2. Patients with pulmonary arterial hypertension related to Eisenmenger physiology echocardiographically established as atrial septal defect at least 2 cm effective diameter and/or ventricular septal defect at least 1 cm effective diameter; PAH confirmed via cardiac catheterization: mean pulmonary arterial pressure >25 mm Hg, pulmonary capillary wedge pressure <15 mm Hg and pulmonary vascular resistance >3 mm Hg/l/min.
  3. Patients with documented oxygen saturation up to 90%, and >70% (at rest, with room air).
  4. Patients able to perform a 6-minute walk test at least 150 m, and up to 450 m.
  5. Patients stable for at least 3 months prior to screening.
  6. Bosentan naïve patients.
  7. Female patients who are surgically sterile, postmenopausal or have documented infertility.
  8. Female patients of childbearing potential using one of the following methods of contraception: Barrier-type devices (e.g., condom, diaphragm) used ONLY in combination with a spermicide. A double-barrier method is recommended; intrauterine devices (IUDs); oral or implanted contraceptives, if used in combination with a barrier method.
  9. Patients providing written informed consent.

Exclusion Criteria:

  1. Pregnant patients, nursing mothers.
  2. Patients with left ventricular dysfunction (ejection fraction <40%).
  3. Patients with restrictive lung disease (TLC<70% predicted); obstructive lung disease (FEV1<70% predicted, with FEV1/FVC<60%)
  4. Patients with systolic blood pressure < 85 mm Hg.
  5. Patients with other conditions that may affect the ability to perform a 6-minute walk test.
  6. Patients unable to provide informed consent and comply with the patient protocol.
  7. Patients with known coronary arterial disease.
  8. Patients with serum creatinine >125 µM/l.
  9. Patients with iron deficiency (serum ferritin <10 ng/ml) unless corrected by iron supplement.
  10. Patients with hemoglobin or hematocrit that is more than 30% below the normal range (patients with secondary polycythemia are permitted).
  11. Patients with AST and/or ALT values greater than 3 times the upper limit of normal.
  12. Patients who have started or stopped treatment for PAH within one month of screening, excluding anticoagulation.
  13. Patients who are receiving glyburide (glibenclamide), cyclosporine A or tacrolimus at inclusion or are expected to receive any of these drugs during the study.
  14. Patients who are receiving vasodilators including, but not limited to epoprostenol or prostacyclin analogues, or are expected to receive any of these drugs during the study.
  15. Patients active on organ transplant lists.
  16. Patients taking phosphodiesterase inhibitors or endothelin receptor antagonists (other than bosentan) or any other investigational drugs/devices.
  17. Patients with planned surgical intervention during the study period.
  18. Cardiac catheterization-specific exclusion criteria:

    1. Patients who cannot safely have catheterization performed as indicated.
    2. Patients in whom shunting is not at the atrial or ventricular level.
    3. Patients with nonequal pulmonary venous desaturation that theoretically cannot be corrected with administration of 100% non-rebreather-supplied oxygen.
    4. Patients with nonpulsatile pulmonary blood flow, or with multiple sources of pulmonary blood flow.
    5. Patients with discontinuous pulmonary arteries, peripheral pulmonary arterial or venous stenosis > 25% size of native PA or creating unequal bilateral PA mean pressures, PA band with gradient > 20 mm Hg, tetralogy of fallot/pulmonary atresia, VSD/pulmonary atresia, DORV/pulmonary atresia, truncus arteriosus, scimitar syndrome.
    6. Patients where SVC sampling cannot be performed, or where SVC sampling may be contaminated
    7. Patients with ductus arteriosus.
    8. Patients with mitral or pulmonary venous stenosis, intracavitary LV outflow obstruction, sub, valvar or supravalvar aortic stenosis or aortic coarctation.
    9. Patients with <10 indexed Wood units, greater than moderate mitral regurgitation, mean pulmonary venous pressure > 16 mm Hg, pulmonary venous "v" waves > 20 mm Hg, systemic ventricular end-diastolic pressure > 16 mm Hg; patients with recognized extracardiac systemic venous collaterals to the pulmonary venous circulation, patients with recognized hepatic wedge pressure-inferior vena cava pressure gradient > 12 mm Hg.
    10. Patients (during catheterization) with uncorrectable hypercarbia with pCO2 >55 mm Hg; patients with uncorrectable acidemia with pH <7.34; patients in active pain or distress; unconscious or mechanically ventilated patients; patients with unstable systemic or pulmonary blood flow; systemic arterial or pulmonary artery pressures or hematocrit (change of > 25% during catheterization); unstable cardiac rhythm dissimilar to baseline cardiac rhythm during physical examination assessments for the entire duration of the catheterization excepting nonsustained arrhythmia; patients with documented or recognized air embolism, hemorrhage, cardiac, cerebral or peripheral organ ischemia occurring during or immediately preceding the catheterization.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00317486

Locations
United States, Massachusetts
BACH Pulmonary Hypertension Service
Boston, Massachusetts, United States, 02115
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030-2303
Australia
Royal Prince Alfred Hospital - Central Clinical School
Camperdown, Australia, NSW 2050
The Royal Melbourne Hospital
Victoria, Australia, 3050
Austria
Universitatsklinikum fur Innere Medizin II
Wien, Austria, AT-1090
Belgium
UZ Gasthuisberg
Leuven, Belgium, BE-3000
Canada, Alberta
The Peter Lougheed Centre
Calgary, Alberta, Canada, T1Y 6J4
Canada, Ontario
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
France
Hospital Necker-Enfants Malades
Paris, France, 75007
Germany
Herzzentrum NRW
Bad Oeynhausen, Germany, D-32545
Deutsches Herzzentrum Munchen
Munchen, Germany, D-80636
Italy
University of Bologna
Bologna, Italy, 40138
San Matteo Hospital
Pavia, Italy, 27100
Netherlands
Academisch Ziekenhuis Groningen
Groningen, Netherlands, 9713 GZ
Spain
Unidad Medico Quirurgica de Cardiologia - Edificio General
Madrid, Spain, 28046
United Kingdom
Scottish Vascular Unit - Western Infirmary
Glasgow, United Kingdom, G11 6NT
Royal Brompton Hospital
London, United Kingdom, SW3 6NP
Sponsors and Collaborators
Actelion
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00317486     History of Changes
Other Study ID Numbers: AC-052-405
Study First Received: April 21, 2006
Last Updated: February 11, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
pulmonary arterial hypertension
Eisenmenger physiology
bosentan

Additional relevant MeSH terms:
Hypertension, Pulmonary
Eisenmenger Complex
Hypertension
Lung Diseases
Respiratory Tract Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Vascular Diseases
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014