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Pharmacogenomics in Pulmonary Arterial Hypertension

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ClinicalTrials.gov Identifier: NCT00593905
Recruitment Status : Unknown
Verified January 2012 by Raymond Benza, West Penn Allegheny Health System.
Recruitment status was:  Recruiting
First Posted : January 15, 2008
Last Update Posted : January 24, 2012
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Baylor College of Medicine
Emory University
University of Chicago
Johns Hopkins University
Tufts Medical Center
Sir Mortimer B. Davis - Jewish General Hospital
London Health Sciences Centre
University of Maryland
University of California, San Francisco
University of Calgary
Chest Medical Associates
Columbia University
Lung Diagnostics, Ltd.
Duke University
University of California, Los Angeles
Latter Day Saints Hospital
Louisiana State University Health Sciences Center in New Orleans
Massachusetts General Hospital
Mayo Clinic
Medical College of Wisconsin
Southeastern Lung Care
Suncoast Lung Center
Children's Hospital Colorado
University Hospitals Cleveland Medical Center
University of Colorado, Denver
University of Michigan
University of Pittsburgh
University of Southern California
The University of Texas Medical Branch, Galveston
Vanderbilt University
Wayne State University
Ohio State University
University of Alabama at Birmingham
Washington University School of Medicine
Sentara Norfolk General Hospital
University of Texas Southwestern Medical Center
Bay Area Chest Physicians
Information provided by (Responsible Party):
Raymond Benza, West Penn Allegheny Health System

January 3, 2008
January 15, 2008
January 24, 2012
July 2005
July 2012   (Final data collection date for primary outcome measure)
6 Minute Walk Test [ Time Frame: 12 months after initiation of drug therapy ]
Same as current
Complete list of historical versions of study NCT00593905 on ClinicalTrials.gov Archive Site
  • Hemodynamics - Right Heart Catheterization [ Time Frame: 12 months after intitation of drug therapy ]
  • Borg [ Time Frame: 12 months after initiation of drug therapy ]
  • Functional Class - FC [ Time Frame: 12 months after intitation of drug therapy ]
  • Toxicities [ Time Frame: 12 months after initiation of drug therapy ]
  • Time of Clinical Worsening [ Time Frame: 12 months after initiation of drug therapy ]
  • Decline in WHO Functional Class [ Time Frame: 12 months after initiation of drug therapy ]
Not Provided
Not Provided
Not Provided
 
Pharmacogenomics in Pulmonary Arterial Hypertension
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

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.

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.***

Observational
Observational Model: Cohort
Not Provided
Retention:   Samples With DNA
Description:
Whole Blood
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.
  • Pulmonary Arterial Hypertension
  • Pulmonary Hypertension
  • PAH WHO Group I
  • Drug: Sitaxsentan
    Sitaxsentan sodium 100 mg tablet every morning
    Other Name: Sitaxsentan-Thelin
  • Drug: Bosentan, Ambrisentan
    Bosentan 125 mg tablet twice daily Ambrisentan 5-10 mg tablet once daily
    Other Names:
    • Bosentan-Tracleer
    • Ambrisentan-Letairis
  • Group 1

    GROUP 1

    1. Patients have to be currently enrolled or previously enrolled in STRIDE FPH01, FPH01-XC FPH02, FPH02x, FPH03, FPH04 or FPH06.
    2. 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.
    Intervention: Drug: Sitaxsentan
  • Group 2

    Group 2

    1. Patients currently receiving bosentan or ambrisentan OR who have previously received bosentan or ambrisentan for greater than 4 (four) months.
    2. 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.
    Intervention: Drug: Bosentan, Ambrisentan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Unknown status
1300
1080
July 2013
July 2012   (Final data collection date for primary outcome measure)

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).
Sexes Eligible for Study: All
Child, Adult, Older Adult
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00593905
RC-4590
RC #4590 ( Other Identifier: Allegheny General Hospital )
Yes
Not Provided
Not Provided
Raymond Benza, West Penn Allegheny Health System
West Penn Allegheny Health System
  • National Institutes of Health (NIH)
  • Baylor College of Medicine
  • Emory University
  • University of Chicago
  • Johns Hopkins University
  • Tufts Medical Center
  • Sir Mortimer B. Davis - Jewish General Hospital
  • London Health Sciences Centre
  • University of Maryland
  • University of California, San Francisco
  • University of Calgary
  • Chest Medical Associates
  • Columbia University
  • Lung Diagnostics, Ltd.
  • Duke University
  • University of California, Los Angeles
  • Latter Day Saints Hospital
  • Louisiana State University Health Sciences Center in New Orleans
  • Massachusetts General Hospital
  • Mayo Clinic
  • Medical College of Wisconsin
  • Southeastern Lung Care
  • Suncoast Lung Center
  • Children's Hospital Colorado
  • University Hospitals Cleveland Medical Center
  • University of Colorado, Denver
  • University of Michigan
  • University of Pittsburgh
  • University of Southern California
  • The University of Texas Medical Branch, Galveston
  • Vanderbilt University
  • Wayne State University
  • Ohio State University
  • University of Alabama at Birmingham
  • Washington University School of Medicine
  • Sentara Norfolk General Hospital
  • University of Texas Southwestern Medical Center
  • Bay Area Chest Physicians
Principal Investigator: Raymond L Benza, MD Allegheny General Hospital/Allegheny-Singer Research Institute of West Penn Allegheny Health System
West Penn Allegheny Health System
January 2012