Ignite Creation Date:
2025-12-25 @ 3:24 AM
Ignite Modification Date:
2026-03-01 @ 1:58 AM
Study NCT ID:
NCT00593905
Status:
WITHDRAWN
Last Update Posted:
2021-12-09
First Post:
2008-01-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pharmacogenomics in Pulmonary Arterial Hypertension
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000081029', 'term': 'Pulmonary Arterial Hypertension'}, {'id': 'D006976', 'term': 'Hypertension, Pulmonary'}, {'id': 'D065627', 'term': 'Familial Primary Pulmonary Hypertension'}], 'ancestors': [{'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D006973', 'term': 'Hypertension'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C106276', 'term': 'sitaxsentan'}, {'id': 'D000077300', 'term': 'Bosentan'}, {'id': 'C467894', 'term': 'ambrisentan'}], 'ancestors': [{'id': 'D000096926', 'term': 'Benzenesulfonamides'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Whole Blood'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'OTHER', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'study not started not an ACT', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2005-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-11', 'completionDateStruct': {'date': '2012-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-11-29', 'studyFirstSubmitDate': '2008-01-03', 'studyFirstSubmitQcDate': '2008-01-03', 'lastUpdatePostDateStruct': {'date': '2021-12-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2008-01-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '6 Minute Walk Test', 'timeFrame': '12 months after initiation of drug therapy'}], 'secondaryOutcomes': [{'measure': 'Hemodynamics - Right Heart Catheterization', 'timeFrame': '12 months after intitation of drug therapy'}, {'measure': 'Borg', 'timeFrame': '12 months after initiation of drug therapy'}, {'measure': 'Functional Class - FC', 'timeFrame': '12 months after intitation of drug therapy'}, {'measure': 'Toxicities', 'timeFrame': '12 months after initiation of drug therapy'}, {'measure': 'Time of Clinical Worsening', 'timeFrame': '12 months after initiation of drug therapy'}, {'measure': 'Decline in WHO Functional Class', 'timeFrame': '12 months after initiation of drug therapy'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Pulmonary Arterial Hypertension', 'Pulmonary Hypertension', 'Pharmacogenomics', 'DNA Testing', 'sitaxsentan', 'bosentan', 'ambrisentan', 'elevated pulmonary artery pressures', 'Letairis', 'Tracleer', 'Thelin', 'Primary Pulmonary Hypertension', 'Pulmonary Artery'], 'conditions': ['Pulmonary Arterial Hypertension', 'Pulmonary Hypertension', 'PAH WHO Group I']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'http://www.phassociation.org', 'label': 'Pulmonary Hypertension Association website'}]}, 'descriptionModule': {'briefSummary': '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.\n\nHypothesis: 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.\n\nThis 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.', 'detailedDescription': '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:\n\nAim 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.\n\nAim 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.\n\nAim 3: Characterize the relationship between any treatment effect, these polymorphisms and PAH severity, using either clinical data or clinical surrogates for disease activity.\n\n\\*\\*\\*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.\\*\\*\\*'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': '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.', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\nGROUP 1\n\n* Patients have to be currently enrolled or previously enrolled in STRIDE FPH01, FPH01-XC FPH02, FPH02x, FPH03, FPH04 or FPH06.\n* 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.\n\nGROUP 2\n\n* Patients currently receiving bosentan or ambrisentan OR who have previously received bosentan or ambrisentan for greater than 4 (four) months.\n* 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.\n\nExclusion Criteria:\n\nGROUP 1\n\n* Not enrolled in the Encysive Pharmaceutical's STRIDE study(sitaxsentan).\n* Known infectious disease (HIV, Hepatitis).\n\nGROUP 2\n\n* Never enrolled in the STRIDE study for sitaxsentan patients.\n* Not currently or previously on bosentan or ambrisentan.\n* Patients who were previously on bosentan or ambrisentan must have been on bosentan or ambrisentan for greater than 4 months.\n* Known infectious disease (HIV, Hepatitis)."}, 'identificationModule': {'nctId': 'NCT00593905', 'briefTitle': 'Pharmacogenomics in Pulmonary Arterial Hypertension', 'organization': {'class': 'OTHER', 'fullName': 'West Penn Allegheny Health System'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'RC-4590'}, 'secondaryIdInfos': [{'id': 'RC #4590', 'type': 'OTHER', 'domain': 'Allegheny General Hospital'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'Group 1', 'description': 'GROUP 1\n\n1. Patients have to be currently enrolled or previously enrolled in STRIDE FPH01, FPH01-XC FPH02, FPH02x, FPH03, FPH04 or FPH06.\n2. 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.', 'interventionNames': ['Drug: Sitaxsentan']}, {'label': 'Group 2', 'description': 'Group 2\n\n1. Patients currently receiving bosentan or ambrisentan OR who have previously received bosentan or ambrisentan for greater than 4 (four) months.\n2. 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.', 'interventionNames': ['Drug: Bosentan, Ambrisentan']}], 'interventions': [{'name': 'Sitaxsentan', 'type': 'DRUG', 'otherNames': ['Sitaxsentan-Thelin'], 'description': 'Sitaxsentan sodium 100 mg tablet every morning', 'armGroupLabels': ['Group 1']}, {'name': 'Bosentan, Ambrisentan', 'type': 'DRUG', 'otherNames': ['Bosentan-Tracleer', 'Ambrisentan-Letairis'], 'description': 'Bosentan 125 mg tablet twice daily Ambrisentan 5-10 mg tablet once daily', 'armGroupLabels': ['Group 2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '15212', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Allegheny General Hospital', 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}], 'overallOfficials': [{'name': 'Raymond L Benza, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Allegheny General Hospital/Allegheny-Singer Research Institute of West Penn Allegheny Health System'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'West Penn Allegheny Health System', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institutes of Health (NIH)', 'class': 'NIH'}, {'name': 'Baylor College of Medicine', 'class': 'OTHER'}, {'name': 'Emory University', 'class': 'OTHER'}, {'name': 'University of Chicago', 'class': 'OTHER'}, {'name': 'Johns Hopkins University', 'class': 'OTHER'}, {'name': 'Tufts Medical Center', 'class': 'OTHER'}, {'name': 'Sir Mortimer B. Davis - Jewish General Hospital', 'class': 'OTHER'}, {'name': 'London Health Sciences Centre', 'class': 'OTHER'}, {'name': 'University of Maryland, College Park', 'class': 'OTHER'}, {'name': 'University of California, San Francisco', 'class': 'OTHER'}, {'name': 'University of Calgary', 'class': 'OTHER'}, {'name': 'Chest Medical Associates', 'class': 'UNKNOWN'}, {'name': 'Columbia University', 'class': 'OTHER'}, {'name': 'Lung Diagnostics, Ltd.', 'class': 'UNKNOWN'}, {'name': 'Duke University', 'class': 'OTHER'}, {'name': 'University of California, Los Angeles', 'class': 'OTHER'}, {'name': 'Latter Day Saints Hospital', 'class': 'OTHER'}, {'name': 'Louisiana State University Health Sciences Center in New Orleans', 'class': 'OTHER'}, {'name': 'Massachusetts General Hospital', 'class': 'OTHER'}, {'name': 'Mayo Clinic', 'class': 'OTHER'}, {'name': 'Medical College of Wisconsin', 'class': 'OTHER'}, {'name': 'Southeastern Lung Care', 'class': 'UNKNOWN'}, {'name': 'Suncoast Lung Center', 'class': 'UNKNOWN'}, {'name': "Children's Hospital Colorado", 'class': 'OTHER'}, {'name': 'University Hospitals Cleveland Medical Center', 'class': 'OTHER'}, {'name': 'University of Colorado, Denver', 'class': 'OTHER'}, {'name': 'University of Michigan', 'class': 'OTHER'}, {'name': 'University of Pittsburgh Medical Center', 'class': 'OTHER'}, {'name': 'University of Southern California', 'class': 'OTHER'}, {'name': 'The University of Texas Medical Branch, Galveston', 'class': 'OTHER'}, {'name': 'Vanderbilt University', 'class': 'OTHER'}, {'name': 'Wayne State University', 'class': 'OTHER'}, {'name': 'Ohio State University', 'class': 'OTHER'}, {'name': 'University of Alabama at Birmingham', 'class': 'OTHER'}, {'name': 'Washington University School of Medicine', 'class': 'OTHER'}, {'name': 'Sentara Norfolk General Hospital', 'class': 'OTHER'}, {'name': 'University of Texas Southwestern Medical Center', 'class': 'OTHER'}, {'name': 'Bay Area Chest Physicians', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': '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', 'investigatorFullName': 'Dawnmarie DeFazio', 'investigatorAffiliation': 'West Penn Allegheny Health System'}}}}