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.
MedDRA version: 9.1Level: LLTClassification code 10064911Term: Pulmonary arterial hypertension

Registration Number: EUCTR2004-000478-30-CZ

Lead Sponsor: Actelion Pharmaceuticals Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 170

Inclusion Criteria

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? no
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

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 = 10 mmHg and
with a normal cardiac index (= 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
• Recently started (< 8 weeks prior to randomization) or planned
cardio-pulmonary rehabilitation program based on exercise
• Treatment or planned treatment with another investigational
drug within 3 months of randomization
• 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
• Treatment for PAH within one month of randomization,
excluding sildenafil treatment (if present for at least 2 months
before randomization, at a stable dose not lower than 20 mg
TID), calcium channel blockers (if present for at least 1 month
before randomization) and anticoagulants
• Treatment with calcineurin-inhibitors (e.g., cyclosporine A and
tacrolimus), fluconazole, glibenclamide (glyburide) within 1
week of randomization
• Known hypersensitivity to bosentan or any of the excipients
• Previous exposure to bosentan

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

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