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Pharmacogenomics in Pulmonary Arterial Hypertension

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by West Penn Allegheny Health System.
Recruitment status was  Recruiting
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
ClinicalTrials.gov Identifier:
NCT00593905
First received: January 3, 2008
Last updated: January 20, 2012
Last verified: January 2012
History of Changes
  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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by West Penn Allegheny Health System:

Primary Outcome Measures:
  • 6 Minute Walk Test [ Time Frame: 12 months after initiation of drug therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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

  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.
 Drug: Sitaxsentan
Sitaxsentan sodium 100 mg tablet every morning
Other Name: Sitaxsentan-Thelin
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.
 Drug: Bosentan, Ambrisentan
Bosentan 125 mg tablet twice daily Ambrisentan 5-10 mg tablet once daily
Other Names:
  • Bosentan-Tracleer
  • Ambrisentan-Letairis

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
Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
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.
Criteria

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 Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00593905

Contacts
Contact: Andrea L Nowicki, BA 412.359.3653 phgenotype@wpahs.org
Contact: Raymond L Benza, MD 412.359.3584 rbenza@wpahs.org

Locations
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         
Sponsors and Collaborators
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
Investigators
Principal Investigator: Raymond L Benza, MD Allegheny General Hospital/Allegheny-Singer Research Institute of West Penn Allegheny Health System
  More Information

Additional Information:
Pulmonary Hypertension Association website  This link exits the ClinicalTrials.gov site

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
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
 Respiratory Tract Diseases
Sitaxsentan
Bosentan
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents

ClinicalTrials.gov processed this record on September 30, 2016