Endothelin antagonist trial in mildly symptomatic PAH patientsA randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy, safety, and tolerability of bosentan in patients with mildly symptomatic pulmonary arterial hypertension.
| DEC-NET Serial number ES577 | |
| Published online | 02/05/2006 11.13.00 |
| Last updated | 02/05/2006 11.12.19 |
| Other protocol ID number | N/A |
| Current trial status | Open (actively recruiting new participants) |
| Major Disease (ICD9 class) | PRIMARY PULMONARY HYPERTENSION |
| Experimental drug | |
| Bosentan | |
| Gender | Both |
| Age (range) | |
Eligibility criteria | |
| Inclusion criteria | |
| Signed informed consent Men or women ³ 12 years of age (women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception) PAH in modified NYHA functional class II due to: -PAH idiopathic (Primary Pulmonary Hypertension) -PAH secondary to human immunodeficiency virus (HIV) -PAH secondary to anorexigens -PAH secondary to atrial septum defect (ASD) < 2 cm, ventricular septum defect (VSD) < 1 cm or patent ductus arteriosus (PDA) -PAH secondary to connective tissue or auto-immune diseases 6-minute walk test (6MWT) distance < 80% of normal predicted value Mean pulmonary arterial pressure (mPAP) ³ 25 mmHg, pulmonary capillary wedge pressure (PCWP) < 15 mmHg, and pulmonary vascular resistance (PVR) at rest ³ 500 dyn.sec.cm-5 | |
| Exclusion criteria | |
| ·PAH associated with conditions other than those mentioned above, e.g., PAH secondary to portal hypertension, complex congenital heart disease or reverse shunt ·Severe obstructive lung disease: FEV1/FVC < 0.5 ·Total lung capacity < 80% of normal predicted value ·Significant vasoreactivity during right heart catheterization: i.e., a fall in mPAP to < 40 mmHg with a decrease ³ 10 mmHg and with a normal cardiac index (³ 2.5 l/min.m2) ·Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements (in particular with 6MWT) ·Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements ·Symptomatic lower limb vascular disease ·HIV patient with opportunistic infection ·Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C ·AST and/or ALT > 3 times the upper limit of normal ranges. ·Hemoglobin concentration < 75% the lower limit of normal ranges ·Systolic blood pressure < 85 mmHg ·Pregnancy or breast-feeding. (others...) | |
Trial design/methodology | |
| Phase | 3 |
| Kind of study | Efficacy Safety |
| Design | Controlled Randomised Blinded Double blind |
| Purpose of study | |
| Primary Objective: To demonstrate that bosentan improves exercise capacity and/or cardiac hemodynamics in mildly symptomatic PAH patients. Secondary Objectives: To demonstrate that bosentan delays time to clinical worsening, and improves dyspnea, NYHA Class, and quality of life. To demonstrate that bosentan is safe and well tolerated in this patient population. | |
| Primary outcomes | |
| ·Change from baseline to Month 6 in 6MWT distance ·Change from baseline to Month 6 in PVR at rest. | |
| Secondary outcomes | |
| ·Time to clinical worsening up to Month 6 and End-of-Study (EOS) ·Change from baseline to Month 6 and EOS in modified NYHA functional class ·Change from baseline to Month 6 and EOS in Borg dyspnea index. ·Change from baseline to Month 6 in mean right atrial pressure (mRAP), mPAP, cardiac index (CI), mixed venous oxygen saturation (SVO2) at rest | |
| Principal investigator | |
| Name | Dr. Joan Albert Barberà |
| Institution | Hospital Clínic Barcelona |
| Postal address | |
| City | |
| Country | |
| Phone | |
| Fax | |
| Promoter |
| ACTELION Pharmaceuticals Ltd. (Industry) |
| Participating centres |
| Hospital Universitario 12 de Octubre (Madrid) |
| Hospital Vall d.Hebron (Barcelona) |
| Hospital Clínic (Barcelona) |
| ISRCTN | EudraCT 2004-000478-30 |
