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

Hamilton Health Sciences Corporation10 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hypertension, Pulmonary Connective Tissue Disease

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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)

Time frame: 6 months

Secondary Outcomes

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)