Pharmacogenomics in Pulmonary Arterial Hypertension

NCT ID: NCT00593905

Last Updated: 2021-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2005-07-31

Study Completion Date

2012-07-31

Brief Summary

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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.

Detailed Description

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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.\*\*\*

Conditions

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Pulmonary Arterial Hypertension Pulmonary Hypertension PAH WHO Group I

Keywords

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Pulmonary Arterial Hypertension Pulmonary Hypertension Pharmacogenomics DNA Testing sitaxsentan bosentan ambrisentan elevated pulmonary artery pressures Letairis Tracleer Thelin Primary Pulmonary Hypertension Pulmonary Artery

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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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.

Sitaxsentan

Intervention Type DRUG

Sitaxsentan sodium 100 mg tablet every morning

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.

Bosentan, Ambrisentan

Intervention Type DRUG

Bosentan 125 mg tablet twice daily Ambrisentan 5-10 mg tablet once daily

Interventions

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Sitaxsentan

Sitaxsentan sodium 100 mg tablet every morning

Intervention Type DRUG

Bosentan, Ambrisentan

Bosentan 125 mg tablet twice daily Ambrisentan 5-10 mg tablet once daily

Intervention Type DRUG

Other Intervention Names

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Sitaxsentan-Thelin Bosentan-Tracleer Ambrisentan-Letairis

Eligibility 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).
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role collaborator

University of Chicago

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

Tufts Medical Center

OTHER

Sponsor Role collaborator

Sir Mortimer B. Davis - Jewish General Hospital

OTHER

Sponsor Role collaborator

London Health Sciences Centre

OTHER

Sponsor Role collaborator

University of Maryland, College Park

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

University of Calgary

OTHER

Sponsor Role collaborator

Chest Medical Associates

UNKNOWN

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role collaborator

Lung Diagnostics, Ltd.

UNKNOWN

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role collaborator

Latter Day Saints Hospital

OTHER

Sponsor Role collaborator

Louisiana State University Health Sciences Center in New Orleans

OTHER

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role collaborator

Medical College of Wisconsin

OTHER

Sponsor Role collaborator

Southeastern Lung Care

UNKNOWN

Sponsor Role collaborator

Suncoast Lung Center

UNKNOWN

Sponsor Role collaborator

Children's Hospital Colorado

OTHER

Sponsor Role collaborator

University Hospitals Cleveland Medical Center

OTHER

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role collaborator

University of Pittsburgh Medical Center

OTHER

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role collaborator

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role collaborator

Vanderbilt University

OTHER

Sponsor Role collaborator

Wayne State University

OTHER

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role collaborator

Sentara Norfolk General Hospital

OTHER

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role collaborator

Bay Area Chest Physicians

OTHER

Sponsor Role collaborator

West Penn Allegheny Health System

OTHER

Sponsor Role lead

Responsible Party

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Dawnmarie DeFazio

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

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Raymond L Benza, MD

Role: PRINCIPAL_INVESTIGATOR

Allegheny General Hospital/Allegheny-Singer Research Institute of West Penn Allegheny Health System

Locations

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Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

Related Links

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http://www.phassociation.org

Pulmonary Hypertension Association website

Other Identifiers

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RC #4590

Identifier Type: OTHER

Identifier Source: secondary_id

RC-4590

Identifier Type: -

Identifier Source: org_study_id