Clinical trial NCT00391443: BUILD 3: Bosentan Use in Interstitial Lung Disease
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: BUILD 3
Idiopathic Pulmonary Fibrosis
Tracleer
Interstitial Lung Disease
bosentan
Actelion
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2006-10-24
Enrollment: 616
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: BUILD 3 is a prospective, multicenter, randomized, double-blind, parallel group, placebo-controlled, event-driven, group sequential, phase III superiority study. The primary objective is to demonstrate that bosentan delays disease worsening or death in patients with Idiopathic Pulmonary Fibrosis.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Male or female 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 American Thoracic Society / European Respiratory Society (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 honeycombing (HC) on baseline high-resolution computed tomography (HRCT) scan.
* Severe concomitant illness limiting life expectancy (\<1 year).
* Severe restrictive lung disease.
* Obstructive lung disease.
* Diffusing capacity of the lung for carbon monoxide \<30% predicted.
* Residual volume \> or = 120% predicted.
* 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.
* Chronic heart failure with New York Heart Association (NYHA) class III/IV or known left ventricular ejection fraction \<25%.
* Alanine aminotransferase (ALT/SGPT) and/or aspartate aminotransferase (AST/SGOT) \> 1.5 times the upper limit of the normal ranges.
* Moderate to severe hepatic impairment.
* Serum creatinine \> or = 2.5 mg/dl 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, 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.

Primary outcomes:
measure: Time to Occurrence of Disease Worsening or Death up to End of Study.
timeFrame: 36 months
Secondary outcomes:
measure: Percentage of Patients Who Experienced Either Disease Worsening or Death at 1 Year.
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Actelion
name: Isabelle Leconte
role: STUDY_DIRECTOR
References:
citation: King TE Jr, Brown KK, Raghu G, du Bois RM, Lynch DA, Martinez F, Valeyre D, Leconte I, Morganti A, Roux S, Behr J. BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 Jul 1;184(1):92-9. doi: 10.1164/rccm.201011-1874OC. Epub 2011 Apr 7.