Pharmacogenomics in Pulmonary Arterial Hypertension

NCT00593905 | Withdrawn DMC

• 2 other identifiers: RC-4590RC #4590
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pulmonary Arterial Hypertension; Pulmonary Hypertension; PAH WHO Group I

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 6 Minute Walk Test

  12 months after initiation of drug therapy

Secondary Outcomes (6)

• Hemodynamics - Right Heart Catheterization

  12 months after intitation of drug therapy

• Borg

  12 months after initiation of drug therapy

• Functional Class - FC

  12 months after intitation of drug therapy

• Toxicities

  12 months after initiation of drug therapy

• Time of Clinical Worsening

  12 months after initiation of drug therapy

Study Arms (2)

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

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

Interventions

Sitaxsentan DRUG

Sitaxsentan sodium 100 mg tablet every morning

Also known as: Sitaxsentan-Thelin

Group 1

Bosentan, Ambrisentan DRUG

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

Also known as: Bosentan-Tracleer, Ambrisentan-Letairis

Group 2

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• West Penn Allegheny Health System: lead
• National Institutes of Health (NIH): collaborator
• Baylor College of Medicine: collaborator
• Emory University: collaborator
• University of Chicago: collaborator
• Johns Hopkins University: collaborator
• Tufts Medical Center: collaborator
• Sir Mortimer B. Davis - Jewish General Hospital: collaborator
• London Health Sciences Centre: collaborator
• University of Maryland, College Park: collaborator
• University of California, San Francisco: collaborator
• University of Calgary: collaborator
• Chest Medical Associates: collaborator
• Columbia University: collaborator
• Lung Diagnostics, Ltd.: collaborator
• Duke University: collaborator
• University of California, Los Angeles: collaborator
• Latter Day Saints Hospital: collaborator
• Louisiana State University Health Sciences Center in New Orleans: collaborator
• Massachusetts General Hospital: collaborator
• Mayo Clinic: collaborator
• Medical College of Wisconsin: collaborator
• Southeastern Lung Care: collaborator
• Suncoast Lung Center: collaborator
• Children's Hospital Colorado: collaborator
• University Hospitals Cleveland Medical Center: collaborator
• University of Colorado, Denver: collaborator
• University of Michigan: collaborator
• University of Pittsburgh Medical Center: collaborator
• University of Southern California: collaborator
• The University of Texas Medical Branch, Galveston: collaborator
• Vanderbilt University: collaborator
• Wayne State University: collaborator
• Ohio State University: collaborator
• University of Alabama at Birmingham: collaborator
• Washington University School of Medicine: collaborator
• Sentara Norfolk General Hospital: collaborator
• University of Texas Southwestern Medical Center: collaborator
• Bay Area Chest Physicians: collaborator

Study Sites (1)

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Related Links

• Pulmonary Hypertension Association website

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Familial Primary Pulmonary Hypertension

Interventions

sitaxsentan; Bosentan; ambrisentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Raymond L Benza, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: 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

Study Record Dates

• First Submitted: January 3, 2008
• First Posted: January 15, 2008
• Study Start: July 1, 2005
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: December 9, 2021

Record last verified: 2021-11

Locations

US (1)