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

Pulmonary Fibrosis Clinical Trial

— IFIGENIA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00639496
• Other study ID #: 7112LAMC01
• Status: Completed
• Phase: Phase 3
• First received: March 13, 2008
• Last updated: March 4, 2015
• Start date: March 2000
• Est. completion date: July 2003

Study information

• Verified date: March 2008
• Source: Zambon SpA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionNetherlands: Medical Ethics Review Committee (METC)United Kingdom: Research Ethics CommitteeBelgium: Institutional Review BoardSpain: Ethics CommitteeItaly: Ethics CommitteeFrance: Institutional Ethical Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: July 2003
• Est. primary completion date: July 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• n-acetylcysteine
600 mg x 3, for 12 months
• placebo
Placebo

Locations

Country	Name	City	State
Belgium	U.Z. Ghent	Gent
France	Hôpital A. Calmette	Lille Cedex
Germany	Klinikum Grosshadern	Munich
Italy	U.O. di Pneumologia-Ospedale	Arezzo
Netherlands	Stichting St. Antonius Ziekenhuis	Nieuwegein
Spain	Hospital Universitario Virgen del Rocío	Sevilla
United Kingdom	The University of Edinburgh-Medical School	Edinburgh

Sponsors (1)

Lead Sponsor	Collaborator
Zambon SpA

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

References & Publications (1)

Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, MacNee W, Thomeer M, Wallaert B, Laurent F, Nicholson AG, Verbeken EK, Verschakelen J, Flower CD, Capron F, Petruzzelli S, De Vuyst P, van den Bosch JM, Rodriguez-Becerra E, Corvasce G, Lankh — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vital capacity (VC) and diffusion capacity for CO (DLCO)		at 6 and 12 months	No
Secondary	clinical, radiologic and physiologic (CRP)-score		at 6 and 12 months	No