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

NCT00639496 | Completed Phase 3 DMC

• 1 other identifier: 7112LAMC01
• Study Type: interventional
• Target: 184
• Locations: 7 countries
• Sites: 7

Brief 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.

Conditions

Pulmonary Fibrosis

Keywords

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• Vital capacity (VC) and diffusion capacity for CO (DLCO)

  at 6 and 12 months

Secondary Outcomes (1)

• clinical, radiologic and physiologic (CRP)-score

  at 6 and 12 months

Study Arms (2)

1

EXPERIMENTAL

patients taking NAC 600 mg t.i.d.

Drug: n-acetylcysteine

2

PLACEBO COMPARATOR

Drug: placebo

Interventions

n-acetylcysteine DRUG

600 mg x 3, for 12 months

Also known as: Flumucil

1

placebo DRUG

Placebo

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Zambon SpA: lead

Study Sites (7)

U.Z. Ghent

Ghent, B- 9000, Belgium

Location

Hôpital A. Calmette

Lille, F 59037, France

Location

Klinikum Grosshadern

Munich, 81377, Germany

Location

U.O. di Pneumologia-Ospedale

Arezzo, 52100, Italy

Location

Stichting St. Antonius Ziekenhuis

Nieuwegein, 3435 CM, Netherlands

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

The University of Edinburgh-Medical School

Edinburgh, EH8 9AG, United Kingdom

Location

Related Publications (2)

• 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, Lankhorst I, Sardina M, Montanari M; IFIGENIA Study Group. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005 Nov 24;353(21):2229-42. doi: 10.1056/NEJMoa042976.

  PMID: 16306520 RESULT

• Behr J, Demedts M, Buhl R, Costabel U, Dekhuijzen RP, Jansen HM, MacNee W, Thomeer M, Wallaert B, Laurent F, Nicholson AG, Verbeken EK, Verschakelen J, Flower CD, Petruzzelli S, De Vuyst P, van den Bosch JM, Rodriguez-Becerra E, Lankhorst I, Sardina M, Boissard G; IFIGENIA study group. Lung function in idiopathic pulmonary fibrosis--extended analyses of the IFIGENIA trial. Respir Res. 2009 Oct 27;10(1):101. doi: 10.1186/1465-9921-10-101.

  PMID: 19860915 DERIVED

MeSH Terms

Conditions

Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• M. Demedts, MD

  U.Z.-Gasthuisberg, Leuven, Belgium

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2008
• First Posted: March 20, 2008
• Study Start: March 1, 2000
• Primary Completion: July 1, 2003
• Study Completion: July 1, 2003
• Last Updated: March 5, 2015

Record last verified: 2008-03

Locations

GB (1); BE (1); FR (1); IT (1); NL (1); DE (1); ES (1)