| Study Summary: |
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This study will make use of a large population of well defined patients with Pulmonary
Arterial Hypertension who were enrolled in Encysive Pharmaceutical's STRIDE clinical trials
or who have received bosentan or ambrisentan for 4 months or longer. This international
study constitutes the largest clinical study of this deadly disease and in such has great
potential to alter the clinical practice by revealing novel gene-drug interactions. This
study tests the hypothesis by executing the following aims:
Aim 1: Determine in Pulmonary Arterial Hypertension (the relationship between known
disease-specific polymorphisms (Serotonin transporter gene and PAI HindIII) and variants in
BMPR2 and SMAD4 with several well-defined clinical efficacy endpoints of sitaxsentan,
bosentan, and ambrisentan therapy.
Aim 2: Determine in Pulmonary Arterial Hypertension the relationship between existing
potentially "therapy-specific" polymorphisms in the ET-1, ETAR, ETBR, NPR-C, prostacyclin
receptor and prostacyclin synthase with several well-defined clinical efficacy endpoints of
sitaxsentan, bosentan, and ambrisentan therapy.
Aim 3: Characterize the relationship between any treatment effect, these polymorphisms and
PAH severity, using either clinical data or clinical surrogates for disease activity.
***This study was funded by the NIH from 2005 - 2009. In August 2009 a no-cost extension
was granted and this study continued until the end of July 2010. Currently the study is
still active and does still have several active sites participating; however, the study is
funded by the internal institution and there is no contributing federal funding.***
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| Criteria: |
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Inclusion Criteria:
GROUP 1
- Patients have to be currently enrolled or previously enrolled in STRIDE FPH01,
FPH01-XC FPH02, FPH02x, FPH03, FPH04 or FPH06.
- WHO Group 1 Pulmonary Arterial Hypertension: Idiopathic, Familial, Associated with
(APAH) Collagen vascular disease, congenital systemic-to-pulmonary shunts, portal
hypertension, Drugs and toxins (e.g., anorexigens, rapeseed oil, L-tryptophan,
methamphetamine, and cocaine), other (thyroid disorders, glycogen storage disease,
Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies,
myeloproliferative disorders, splenectomy) Associated with significant venous or
capillary involvement, Pulmonary veno-occlusive disease, Pulmonary-capillary
hemangiomatosis.
GROUP 2
- Patients currently receiving bosentan or ambrisentan OR who have previously received
bosentan or ambrisentan for greater than 4 (four) months.
- WHO Group 1 Pulmonary Arterial Hypertension: Idiopathic, Familial, Associated with
(APAH), collagen vascular disease, congenital systemic-to-pulmonary shunts, portal
hypertension, drugs and toxins (e.g., anorexigens, rapeseed oil, L-tryptophan,
methamphetamine, and cocaine), other (thyroid disorders, glycogen storage disease,
Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies,
myeloproliferative disorders, or splenectomy), associated with significant venous or
capillary involvement, pulmonary veno-occlusive disease, or pulmonary capillary
hemangiomatosis.
Exclusion Criteria:
GROUP 1
- Not enrolled in the Encysive Pharmaceutical's STRIDE study(sitaxsentan).
- Known infectious disease (HIV, Hepatitis).
GROUP 2
- Never enrolled in the STRIDE study for sitaxsentan patients.
- Not currently or previously on bosentan or ambrisentan.
- Patients who were previously on bosentan or ambrisentan must have been on bosentan or
ambrisentan for greater than 4 months.
- Known infectious disease (HIV, Hepatitis).
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