Pharmacogenomics in Pulmonary Arterial Hypertension
Recruitment status was Recruiting
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
Our goal is to determine clinically in Pulmonary Arterial Hypertension patients if associations exist between the efficacy and toxicity of sitaxsentan, bosentan, and ambrisentan and several gene polymorphisms in several key disease-specific and therapy specific genes. Also characterized is the relationship between these polymorphisms and the severity of Pulmonary Arterial Hypertension using either baseline hemodynamic or clinical surrogates for disease severity.
Hypothesis: Polymorphisms influence the efficacy and toxicity of specific Pulmonary Arterial Hypertension therapy as well as development/severity of PAH via their effect on PA remodeling, drug response, or metabolism.
This study requires a one time 8.5 ml blood sample and clinical data to be obtained at initiation of therapy, 4 months after initiation of therapy and 12 months after initiation of therapy.
| Condition | Intervention |
|---|---|
|
Pulmonary Arterial Hypertension Pulmonary Hypertension PAH WHO Group I |
Drug: Sitaxsentan Drug: Bosentan, Ambrisentan |
| Study Type: | Observational |
| Study Design: | Observational Model: Cohort |
| Official Title: | Pharmacogenomics in Pulmonary Arterial Hypertension: A Multi-Center International Study to Determine Whether in PAH Patients Clinical Associations Exist Between the Efficacy and Toxicity of Endothelin Receptor Antagonists and Several Gene Polymorphisms in Several Key Disease-Specific and Therapy Specific Genes |
- 6 Minute Walk Test [ Time Frame: 12 months after initiation of drug therapy ] [ Designated as safety issue: No ]
- Hemodynamics - Right Heart Catheterization [ Time Frame: 12 months after intitation of drug therapy ] [ Designated as safety issue: No ]
- Borg [ Time Frame: 12 months after initiation of drug therapy ] [ Designated as safety issue: No ]
- Functional Class - FC [ Time Frame: 12 months after intitation of drug therapy ] [ Designated as safety issue: No ]
- Toxicities [ Time Frame: 12 months after initiation of drug therapy ] [ Designated as safety issue: No ]
- Time of Clinical Worsening [ Time Frame: 12 months after initiation of drug therapy ] [ Designated as safety issue: No ]
- Decline in WHO Functional Class [ Time Frame: 12 months after initiation of drug therapy ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
Whole Blood
| Estimated Enrollment: | 1300 |
| Study Start Date: | July 2005 |
| Estimated Study Completion Date: | July 2013 |
| Estimated Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Groups/Cohorts | Assigned Interventions |
|---|---|
|
Group 1
GROUP 1
|
Drug: Sitaxsentan
Sitaxsentan sodium 100 mg tablet every morning
Other Name: Sitaxsentan-Thelin
|
|
Group 2
Group 2
|
Drug: Bosentan, Ambrisentan
Bosentan 125 mg tablet twice daily Ambrisentan 5-10 mg tablet once daily
Other Names:
|
Detailed Description:
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.***
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Patients must have been diagnosed with WHO Group 1 Pulmonary Arterial Hypertension: Idiopathic, Familial or Associated with (APAH) Collagen vascular disease, congenital systemic-to-pulmonary shunts, portal hypertension, Drugs and toxins , 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. Patients currently therapy must include sitaxsentan, bosentan, or ambrisentan OR patients must have previously been treated with sitaxsentan, bosentan or ambrisentan for 4 months or longer.
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).
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00593905
| Contact: Andrea L Nowicki, BA | 412.359.3653 | phgenotype@wpahs.org | |
| Contact: Raymond L Benza, MD | 412.359.3584 | rbenza@wpahs.org |
| United States, Pennsylvania | |
| Allegheny General Hospital | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15212 | |
| Contact: Andrea L Nowicki, BA 412-359-3653 anowicki@wpahs.org | |
| Contact: Raymond L Benza, MD 412.359.3584 rbenza@wpahs.org | |
| Principal Investigator: Raymond L Benza, MD | |
| Principal Investigator: | Raymond L Benza, MD | Allegheny General Hospital/Allegheny-Singer Research Institute of West Penn Allegheny Health System |
More Information
Additional Information:
No publications provided
| Responsible Party: | Raymond Benza, Professor of Medicine, Drexel University College of Medicine, James Magovern Chair for Cardiovascular Research Director and Section Head Advanced Heart Failure, Transplant, Mechanical Circulatory Support and Pulmonary Hypertension Programs, West Penn Allegheny Health System |
| ClinicalTrials.gov Identifier: | NCT00593905 History of Changes |
| Other Study ID Numbers: | RC-4590, RC #4590 |
| Study First Received: | January 3, 2008 |
| Last Updated: | January 20, 2012 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration Canada: Ethics Review Committee Germany: Ethics Commission Mexico: Ethics Committee Netherlands: Independent Ethics Committee Poland: Ministry of Health Spain: Ethics Committee United Kingdom: Research Ethics Committee Australia: National Health and Medical Research Council Belgium: Federal Agency for Medicinal Products and Health Products |
Keywords provided by West Penn Allegheny Health System:
|
Pulmonary Arterial Hypertension Pulmonary Hypertension Primary Pulmonary Hypertension Pharmacogenomics DNA Testing sitaxsentan bosentan |
ambrisentan elevated pulmonary artery pressures Letairis Tracleer Thelin Pulmonary Artery |
Additional relevant MeSH terms:
|
Hypertension Hypertension, Pulmonary Cardiovascular Diseases Lung Diseases Respiratory Tract Diseases Vascular Diseases |
Bosentan Antihypertensive Agents Cardiovascular Agents Pharmacologic Actions Therapeutic Uses |
ClinicalTrials.gov processed this record on March 03, 2015