Effects of bosentan on morbidity and mortality in patients with Idiopathic Pulmonary Fibrosis - a multicenter, double-blind, randomized, placebo-controlled, parallel group, event-driven, group sequential, phase III study

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

•Signed informed consent.
•Male or female patients aged 18 years or older (females of child-bearing potential must have been surgically sterilized or use a reliable method of contraception).
•Proven diagnosis of IPF according to ATS/ERS statement, of < 3 years, with surgical lung biopsy (SLB).

Exclusion Criteria

•Interstitial lung disease due to conditions other than IPF.
•Presence of extensive honeycomb (HC) on Baseline high-resolution computed tomography (HRCT) scan.
The patient is not allowed in BUILD 3 if HC involves more than 5 % of the parenchyma in 3 or more of the 6 zones (i.e., right and left lung, viewed at the levels of tracheal carina, inferior pulmonary veins, and 1 cm above the dome of the diaphragm), whether the involvement is unilateral or bilateral.
•Severe concomitant illness limiting life expectancy (< 1 year).
•Severe restrictive lung disease: forced vital capacity (FVC) < 50% predicted, or FVC < 1.2 liter.
•Diffusing capacity of the lung for carbon monoxide (DLCO) < 30% predicted.
•Residual volume * 120% predicted.
•Obstructive lung disease: forced expiratory volume in 1 second (FEV1)/FVC < 0.65.
•Documented sustained improvement of patient's IPF condition up to 12 months prior to randomization with or without IPF-specific therapy.
•Recent pulmonary or upper respiratory tract infection (up to 4 weeks prior to randomization).
•Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (e.g., pulmonary function tests).
•Chronic heart failure with NYHA class III/IV or known left ventricular ejection fraction < 25%.
•ALT/SGPT and/or AST/SGOT > 1.5 times the upper limit of the normal ranges (ULN).
•Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
•Serum creatinine >= 2.5 mg/dl (221 *mol/l) or chronic dialysis.
•Hemoglobin concentration < 75% the lower limit of the normal ranges.
•Systolic blood pressure < 85 mmHg.
•Pregnancy or breast-feeding.
•Current drug or alcohol dependence.
•Chronic treatment with the following drugs prescribed for IPF (within 4 weeks of randomization):
- Oral corticosteroids (> 20 mg/day of prednisone or equivalent),
- Immunosuppressive or cytotoxic drugs,
- Antifibrotic drugs including pirfenidone, D-penicillamine, colchicine,TNFalfa blocker, imatinib, interferon *, cyclophosphamide, azathioprine,
- Chronic use of N-acetylcysteine (prescribed for IPF).
•Oral anticoagulants other than those indicated for a venous or arterial thrombotic disease.
•Treatment with glibenclamide (glyburide) and calcineurin inhibitors (cyclosporine A, tacrolimus) up to 1 week prior to randomization.
•Treatment with an endothelin receptor antagonist up to 3 months prior to randomization.
•Participation in the BUILD 1 trial.
•Treatment with another investigational drug up to 3 months prior to randomization or planned treatment.
•Known hypersensitivity to bosentan or any of the excipients.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary end-point: Time to occurrence of disease worsening or death up to EOS.<br /><br>- Disease worsening is defined as worsening of PFTs or acute exacerbation of<br /><br>IPF.<br /><br>1) Worsening of PFTs (confirmed by two tests at least 4 weeks apart) is defined<br /><br>as the occurrence of both:<br /><br>- Decrease from baseline >= 10% in FVC (absolute values, i.e., liters)<br /><br>and<br /><br>- Decrease from baseline >= 15% in DLCO (absolute values, i.e., ml.mmHg -1.min-1)<br /><br>2) Acute exacerbation of IPF is defined as:<br /><br>An unexplained rapid deterioration of patient*s condition within 4 weeks with<br /><br>an increasing shortness of breath requiring hospitalization and oxygen<br /><br>supplementation >= 5 liters/min to maintain a resting SaO2 >= 90% or PaO2 >= 55<br /><br>mmHg (sea level) or 50 mmHg (high altitude).</p><br>

Secondary Outcome Measures

Name	Time	Method

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