study of the effects of high-dose n-acetylcysteine (nac) in idiopathic pulmonary fibrosis (ipf)

Conditions: Pulmonary Fibrosis

Summary: the purpose of this study is to determine whether nac added to prednisone, and azathioprine has a better effect on lung function, radiology and clinical condition than placebo + prednisone in combination with azathioprine after 6 and 12 months.


Eligibility criteria:
inclusion criteria: * diagnosis of ipf according to the international consensus statement * bronchoalveolar lavage (bal) showing no features to support an alternative diagnosis. * patients in whom it was possible to determine single breath dlco. * patients with newly or previously diagnosed ipf, in whom it was clinically justified to use the standardised regimen azathioprine plus prednisone exclusion criteria: * known intolerance to n-acetylcysteine. * patients with respiratory infections at study entry should be excluded until the infections have been treated successfully (vc and dlco comparable with the values before the infection). * patients with pre-existing disease that interferes with the evaluation of ipf: extensive old tbc lesions, significant bronchiectasis, moderate or severe copd. * patients with malignancy in the last 5 years. if the patient had a malignancy in the past and is free of malignancy for more than five years, the patient is regarded as healed. * patients with heart failure. * patients with hepatic function abnormalities contraindicating the use of azathioprine (i.e. clinically significant abnormalities of ptt and/or ggt). * patients with a renal clearance \< 10ml/min and/or hematuria and/or proteinuria of collagen vascular disease origin. a renal clearance is only performed in the presence of an abnormal serum creatinine and/or serum urea level. * patients who are artificially ventilated. * prednisone at a dose \> 0.5 mg/kg/day (or other glucocorticoids such as triamcinolone, dexamethasone or methylprednisolone at an equivalent dose) or azathioprine at a dose \> 2 mg/kg/day during the last month prior to inclusion. * use of other immunosuppressives (such as cyclophosphamide and colchicine) is not allowed in the last month and for the duration of the trial. * any form of anticancer therapy or methotrexate are not allowed when used for more than 1 week in the past and for the duration of the trial. * amiodarone or nitrofurantoin are not allowed in the last 5 years, when used for more than 1 week in the past and for the duration of the trial. * allopurinol, oxypurinol, thiopurinol, anti-oxidants (e.g. vitamin e) or glutathione supplements are not allowed in the last month and during the trial. * the use of interferon or other antifibrotics (e.g. pirfenidone) is not allowed in the past and during the study. * the use of nac therapy at a dosage of more than 600 mg/day is not allowed in the last 3 years for a total period of more than 3 months. * patients suffering or having suffered from documented active ulcer within the last 3 years. * patients in whom the standardised treatment regimen is contraindicated or not justified. * pregnancy. * known or suspected drug or alcohol abuse. * patients on other investigational compounds or participating in clinical trials on investigational compounds within the last 3 months. * patients expected to be non-compliant in taking the medication.

Keywords: idiopathic pulmonary fibrosis