Endothelin antagonist trial in mildly symptomatic PAH patients. A randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy, safety, and tolerability of bosentan in patients with mildly symptomatic pulmonary arterial hypertension. - EARLY
- Conditions
- Patients with modified NYHA functional Class II PAH have mild symptoms, but their pulmonary artery pressures are elevated which leads to increased wall stress and silent heart damage progression. Therefore Class I-II patients have a better survival rate than Class III-IV patients (Odds ratio = 1.9) but will eventually deteriorate if untreated.There are no approved drug therapies for Class II PAH and the EARLY study is the first trial designed to enroll exclusively class II patients.
- Registration Number
- EUCTR2004-000478-30-ES
- Lead Sponsor
- Actelion Pharmaceuticals Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 170
a)Men or women aged 12 years of age and over (except for countries where this age limit is contrary to specific regulatory requirements).
Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination.
–Reliable method of contraception are:
Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide.
Intra-uterine devices.
Oral, injectable or implantable contraceptives only in combination with a barrier method.
–Hormone-based contraceptives alone, regardless of the route of administration, are not considered as reliable methods of contraception.
–Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception.
Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.
b)PAH in modified NYHA functional class II due to:
1.PAH idiopathic (Primary Pulmonary Hypertension)
2.PAH secondary to human immunodeficiency virus (HIV)
3.PAH secondary to anorexigens
4.PAH secondary to atrial septum defect (ASD) < 2 cm, ventricular septum defect (VSD) < 1 cm or patent ductus arteriosus (PAD)
5.PAH secondary to connective tissue or auto-immune diseases
c)6-minute walk test (6MWT) distance < 80% of normal predicted value (see Appendix 3 in protocol)
d)Mean pulmonary arterial pressure (mPAP) 25 mmHg and over, pulmonary capillary wedge pressure (PCWP) < 15 mmHg, and pulmonary vascular resistance (PVR) at rest 500 dyn.sec.cm-5 and over
e)Signed informed consent prior to initiation of any study-mandated procedure.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1)PAH associated with conditions other than those mentioned above, e.g., PAH secondary to portal hypertension, complex congenital heart disease or reverse shunt
2)Severe obstructive lung disease: FEV1/FVC < 0.5
3)Total lung capacity (TLC) < 80% of normal predicted value (see Appendix 4 in protocol)
4)Significant vasoreactivity during right heart catheterization: i.e., a fall in mPAP to < 40 mmHg with a decrease of 10 mmHg and over and with a normal cardiac index ( 2.5 l/min.m2 and over)
5)Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (in particular with 6MWT)
6)Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
7)Symptomatic lower limb vascular disease
8)HIV patient with opportunistic infection
9)Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
10)Aminotransferases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) > 3 times the upper limit of the normal (ULN) range
11)Hemoglobin concentration < 75% of the lower limit of the normal range
12)Systolic blood pressure (BP) < 85 mmHg
13)Pregnancy or breast-feeding
14)Recently started (< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise
15)Treatment or planned treatment with another investigational drug within 3 months of randomization.
16)Treatment with an endothelin receptor antagonist or with prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 3 months of randomization.
17)Treatment for PAH within one month of randomization, excluding calcium channel blockers (if present for at least 1 month before randomization) and anticoagulants.
18)Treatment with calcineurin-inhibitors (e.g., cyclosporine A, tacrolimus), fluconazole, glibenclamide (glyburide) within 1 week of randomization.
19)Known hypersensitivity to bosentan or any of the excipients
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method