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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00317486




Registration number
NCT00317486
Ethics application status
Date submitted
21/04/2006
Date registered
25/04/2006
Date last updated
15/02/2010

Titles & IDs
Public title
Effects of Tracleer (Bosentan) on Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
Scientific 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
Secondary ID [1] 0 0
AC-052-405
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension Related to Eisenmenger Physiology 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - bosentan

Treatment: Drugs: bosentan
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline to Week 16 in oxygen saturation at rest with room air
Timepoint [1] 0 0
Primary outcome [2] 0 0
Change from baseline to Week 16 in indexed pulmonary vascular resistance
Timepoint [2] 0 0
Secondary outcome [1] 0 0
Changes from baseline to Week 16 in cardiac hemodynamics
Timepoint [1] 0 0

Eligibility
Key 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.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2005
Sample size
Target
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Central Clinical School - Camperdown
Recruitment hospital [2] 0 0
The Royal Melbourne Hospital - Victoria
Recruitment postcode(s) [1] 0 0
NSW 2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3050 - Victoria
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
Austria
State/province [3] 0 0
Wien
Country [4] 0 0
Belgium
State/province [4] 0 0
Leuven
Country [5] 0 0
Canada
State/province [5] 0 0
Alberta
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
Germany
State/province [8] 0 0
Bad Oeynhausen
Country [9] 0 0
Germany
State/province [9] 0 0
Munchen
Country [10] 0 0
Italy
State/province [10] 0 0
Bologna
Country [11] 0 0
Italy
State/province [11] 0 0
Pavia
Country [12] 0 0
Netherlands
State/province [12] 0 0
Groningen
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Glasgow
Country [15] 0 0
United Kingdom
State/province [15] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00317486
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00317486