A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease

A Pilot Study to Evaluate the Effect of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease

The primary objectives of this exploratory study are to evaluate the effects of bosentan on hemodynamics (via cardiac catheterization) during exercise in patients with Pulmonary Arterial Hypertension (PAH) who have abnormal hemodynamics during exercise but normal hemodynamics at rest. The authors hypothesize that early treatment may change the course of disease progression by improving hemodynamics during exercise, thus delaying disease progression.

Study Overview

• Status: Unknown
• Conditions: Hypertension, Pulmonary; Connective Tissue Disease
• Intervention / Treatment: Drug: bosentan

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 5G4
      • Victoria Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women ≥ 18 years of age

• For female patients, only non-pregnant women who are surgically sterile, postmenopausal or have documented infertility (over 50 years of age and amenorrheic for at least 1 year), or those of childbearing potential using one of the following methods of contraception:

  • Barrier-type devices (e.g., condom, diaphragm) used ONLY in combination with a spermicide. A double-barrier method is recommended.
  • Intrauterine devices (IUDs)
  • Oral contraceptives, if used in combination with a barrier method
• Body weight of 40 kg or higher
• Patients diagnosed with connective tissue disease

• Hemodynamics at rest, based on cardiac catheterization, should be as follows:

  • Mean pulmonary arterial pressure (mPAP) : 18 - 25 mmHg
  • PCWP ≤ 15 mmHg
• Hemodynamics during exercise, based on cardiac catheterization, should be as follows: mPAP > 30 mmHg
• Provide written informed consent

Exclusion Criteria:

• PAH associated with any other condition
• Severe obstructive lung disease : FEV1∕ FVC <0.5
• Total lung capacity <60% of normal predicted value
• Unable or unwilling have a cardiac catheterization procedure
• Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements (6-MWT)
• Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
• AST and ∕or ALT > 3 times uln
• Hemoglobin concentration > 25% below the lower limit of normal
• Systolic blood pressure < 85 mm Hg
• Pregnancy or breast-feeding
• Treatment or planned treatment with another investigational drug
• Treatment with an endothelin receptor antagonist, phosphodiesterase type 5 inhibitor, or with prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 2 months of inclusion
• Treatment with calcineurin-inhibitors (i.e., cyclosporine A and tacrolimus), fluconazole, glibenclamide (glyburide) within 1 week of study start;
• Known hypersensitivity to bosentan or any of the excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bosentan	Drug: bosentan; bosentan 62mg bid x 4 weeks, followed by bosentan 125mg bid x 20 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome is the change in the following hemodynamics during exercise: pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac output∕cardiac input (CO∕CI), mean right arterial pressure (mRAP)	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in hemodynamics at rest: pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac output/cardiac input (CO∕CI), mean right arterial pressure (mRAP)	6 months

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Actelion
• Investigators: Principal Investigator: Christine Bradley, Hamilton Health Sciences Corporation

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Anticipated): April 1, 2010
• Study Completion (Anticipated): April 1, 2010

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 17, 2009
• First Posted (Estimate): March 18, 2009

Study Record Updates

• Last Update Posted (Estimate): March 18, 2009
• Last Update Submitted That Met QC Criteria: March 17, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Connective Tissue Diseases; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: PAH-CTD-2007