Study of the Effects of High-dose N-acetylcysteine (NAC) in Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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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.

Official Title
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Idiopathic Pulmonary Fibrosis International Group Exploring NAC I Annual Study of the Effects of High-dose N-acetylcysteine (NAC) in Idiopathic Pulmonary Fibrosis (IPF)

Conditions
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Pulmonary Fibrosis

Intervention / Treatment
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* Drug: n-acetylcysteine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>patients taking NAC 600 mg t.i.d. | Drug: n-acetylcysteine<br>* 600 mg x 3, for 12 months<br>* Other names: Flumucil;|
| Placebo Comparator: 2<br> | Drug: placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital capacity (VC) and diffusion capacity for CO (DLCO) |  | at 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical, radiologic and physiologic (CRP)-score |  | at 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic Pulmonary Fibrosis