Status:
COMPLETED
Combination Therapy in Pulmonary Arterial Hypertension
Lead Sponsor:
Actelion
Conditions:
Pulmonary Arterial Hypertension
Eligibility:
All Genders
12+ years
Phase:
PHASE4
Brief Summary
An open label, non-comparative study design is appropriate for this Phase 4 study designed to assess whether a core therapy of bosentan, either as monotherapy or with the addition of sildenafil, enabl...
Eligibility Criteria
Inclusion
- Signed informed consent prior to initiation of any study-mandated procedures.
- Males or females ≥ 12 years of age (females of child-bearing potential must have been surgically sterilized or use a reliable method of contraception).
- Symptomatic patients with the following types of PAH belonging to World Health Organization (WHO) Pulmonary Hypertension Classification Group I:
- Idiopathic (IPAH)
- Familial (FPAH)
- Associated with PAH (APAH):
- Collagen vascular disease
- Drugs and toxins
- Patients naïve to treatment with advanced PAH therapies (i.e., endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE-5) inhibitors or prostacyclins) with a right heart catheterization (RHC) showing all of the following:
- Mean pulmonary arterial pressure (mPAP) ≥ 25 mm Hg
- Pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg or left ventricular end diastolic pressure (LVEDP) ≤ 15 mm Hg when PCWP is not accurately obtained
- Pulmonary vascular resistance ≥ 3 Wood units
- 6-MWT distance ≥ 150 meters and \< 360 meters.
Exclusion
- Patients with Pulmonary Hypertension (PH) belonging to WHO Classification Group II-V.
- Patients with PAH (WHO PH Classification Group I) other than that listed in the Inclusion Criteria.
- Pregnant and/or nursing.
- Women of childbearing potential not using a reliable method of contraception.
- Patients with known human immunodeficiency virus (HIV) infection.
- Patients with significant vasoreactivity during right heart catheterization (i.e., a fall in mPAP to \< 40 mm Hg with a decrease of ≥ 10 mm Hg and with a normal cardiac index ≥ 2.5 l/min.m\^2).
- Patients with restrictive lung disease (i.e., total lung capacity (TLC) \< 60% of normal predicted value).
- Patients with obstructive lung disease (i.e., forced expiratory volume/ forced vital capacity (FEV1/FVC) \< 0.5).
- Patients with impaired left ventricular function (LVEF \<50%) or diastolic dysfunction.
- Patients with portal hypertension, cirrhosis, moderate to severe liver impairment (Child-Pugh Class B or C), or liver enzymes (Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)) \> 3.0 times the upper limit of normal range.
- Treatment with glibenclamide (glyburide) and calcineurin inhibitors (cyclosporine A, tacrolimus) sirolimus, everolimus up to 1 week prior to Baseline (Day 1).
- Patients currently receiving or predicted to require treatment, during the course of the study, with nitrates, protease inhibitors, or alpha-blockers.
- Patients with a hemoglobin concentration \< 75 % of the lower limit of the normal range or \< 8.5 g/dL.
- Patients currently receiving or predicted to require treatment with a prostanoid during the course of the study.
- Patients with systolic blood pressure \< 85 mm Hg.
- Patients with body weight \< 40 kg.
- Patients who have received any investigational product within 90 days prior to Baseline.
- Patients who previously received any advanced therapy for PAH (e.g., ERAs, PDE-5 inhibitors or prostacyclins).
- Patients with hypersensitivity to sildenafil or any excipients of its formulation.
- Patients with any contraindication to sildenafil treatment (i.e., nitrates).
- Patients with any recent medical condition limiting the ability to comply with the study requirements (i.e., stroke, myocardial infarction).
- Patients with unstable PAH whose disease state would prohibit the completion of study procedures, in the opinion of the investigator.
- Patients unable to complete a MRI scan (e.g., claustrophobia).
- Patients with permanent cardiac pacemakers, automatic internal cardioverter defibrillators (AICD's), neurostimulators, hearing aides, and other implanted metallic devices that are contraindicated during a MRI study.
- Patients with conditions that would interfere with proper cardiac gating during MRI, such as atrial fibrillation or multiple premature ventricular contractions (PVCs)/premature atrial contractions (PACs).
- Patients with conditions that prevent compliance with the protocol or the ability to adhere to therapy.
Key Trial Info
Start Date :
March 1 2007
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 1 2010
Estimated Enrollment :
100 Patients enrolled
Trial Details
Trial ID
NCT00433329
Start Date
March 1 2007
End Date
August 1 2010
Last Update
February 4 2025
Active Locations (0)
Enter a location and click search to find clinical trials sorted by distance.
No Results Found
We couldn’t find results for the location/zipcode entered or within the selected range. Please check your input or adjust your search.