Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in People With Idiopathic Pulmonary Fibrosis - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00650091

Purpose

Idiopathic pulmonary fibrosis (IPF) is a long-term lung disease that affects an individual's ability to breathe. This study will evaluate the effectiveness of the antioxidant N-acetylcysteine (NAC), alone and in combination with an established IPF medication regimen, at preventing the loss of lung function in people with IPF.

Condition	Intervention	Phase
Pulmonary Fibrosis	Drug: Prednisone Drug: Azathioprine Drug: N-acetylcysteine (NAC) Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in IPF

Resource links provided by NLM:

MedlinePlus related topics: Pulmonary Fibrosis

Drug Information available for: Prednisone Azathioprine sodium salt Azathioprine Acetylcysteine

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Change in serial forced vital capacity [ Time Frame: Measured at Week 60 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to disease progression [ Time Frame: Measured at Week 60 ] [ Designated as safety issue: No ]
Acute exacerbations [ Time Frame: Measured at Week 60 ] [ Designated as safety issue: No ]
Respiratory infections [ Time Frame: Measured at Week 60 ] [ Designated as safety issue: No ]
Maintained forced vital capacity response [ Time Frame: Measured at Week 60 ] [ Designated as safety issue: No ]

Estimated Enrollment:	390
Study Start Date:	October 2009
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Participants will receive prednisone, azathioprine, and N-acetylcysteine (NAC) for 60 weeks.	Drug: Prednisone Participants will receive 0.5 to 0.15 mg of prednisone once a day. Drug: Azathioprine Participants will receive 1 to 2 mg of azathioprine once a day. Drug: N-acetylcysteine (NAC) Participants will receive 600 mg of NAC three times a day.
2: Active Comparator Participants will receive N-acetylcysteine (NAC) for 60 weeks.	Drug: N-acetylcysteine (NAC) Participants will receive 600 mg of NAC three times a day.
3: Placebo Comparator Participants will receive placebo for 60 weeks.	Drug: Placebo Participants will receive placebo each day.

Detailed Description:

IPF is a disease in which fibrous tissue clogs and damages the air sacs within the lungs. Widespread and permanent scarring and stiffening of lung tissue eventually results. Individuals with IPF may experience breathing difficulties, cough, chest pain, and a decreased exercise capacity. Although the cause of IPF is not definitively known, it may be a result of an inflammatory response to an unknown substance. There is no cure for IPF, but most people with the disease take prednisone, a corticosteroid medication that helps reduce inflammation, and azathioprine, a medication with immune-suppression properties to slow the fibrous growth and scar forming process. NAC, an antioxidant that is effective at loosening up mucus that forms in the lungs, may improve lung function. Adding NAC to the standard treatment regimen of prednisone and azathioprine may be beneficial to people with IPF. The purpose of this study is to evaluate the effectiveness of NAC, alone and in combination with prednisone and azathioprine, at preventing the loss of lung function in people with IPF.

This study will enroll people with mild to moderate IPF. Participants will be randomly assigned to receive for 60 weeks either combination treatment with prednisone, azathioprine, and NAC; NAC alone; or placebo. Study visits will occur at baseline and Weeks 4, 15, 30, 45, and 60. At all study visits, a physical exam and blood collection will occur. At selected visits, the following study procedures will occur: lung function testing; urine collection; a 6-minute walk test, which will measure the distance walked in a 6-minute period; and questionnaires to assess health status, breathing, and quality of life. Participants will record medication usage and symptoms in a daily diary. Study researchers will review medical records and the Social Security death index 5 years after the end of the study to determine the incidence of death among study participants.

Eligibility

Ages Eligible for Study:	35 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Forced vital capacity (FVC) greater than or equal to 50% of predicted value
Diffusion capacity (DLCO) greater than or equal to 30% of predicted value
Diagnosis of IPF by modified American Thoracic Society (ATS) criteria in the 48 months before study entry

Exclusion Criteria:

History of clinically significant environmental exposure known to cause pulmonary fibrosis
Diagnosis of connective tissue disease as the likely cause of the interstitial disease
Extent of emphysema greater than the extent of fibrotic change (i.e., honeycombing, reticular changes) on high resolution computed tomography (HRCT) scan
Forced expiratory volume in 1 second (FEV1)/FVC ratio less than 0.65 at the time of screening (post-bronchodilator)
Partial pressure of arterial oxygen (PaO2) less than 55 mm Hg (less than 50 mm Hg at Denver study site)
Residual volume greater than 120% predicted at the time of screening (post-bronchodilator)
Evidence of active infection
Significant bronchodilator response on screening spirometry, defined as change in FEV1 greater than or equal to 12% and absolute change greater than 200 mL OR change in FVC greater than or equal to 12% and absolute change greater than 200 mL
Screening and baseline FVC measurements (in liters, post-bronchodilator) differing by 11%
Listed for lung transplantation
History of unstable or deteriorating cardiac disease
Heart attack, coronary artery bypass, or angioplasty in the 6 months before study entry
Unstable angina pectoris or congestive heart failure requiring hospitalization in the 6 months before study entry
Uncontrolled arrhythmia
Severe uncontrolled high blood pressure
Known HIV or hepatitis C
Known cirrhosis and chronic active hepatitis
Active substance and/or alcohol abuse
Pregnant or breastfeeding
Women of childbearing potential who are not using a medically approved means of contraception
Any clinically relevant lab abnormalities, including the following:
1. Creatinine greater than twice the upper limit of normal (ULN)
2. Hematology outside of specified limits
  1. White blood cells less than 3,500/mm3
  2. Hematocrit less than 25% or greater than 59%
  3. Platelets less than 100,000 mm3 at the time of screening
3. Any of the following liver function test criteria above specified limits
  1. Total bilirubin greater than twice the ULN
  2. Aspartate (AST) or alanine aminotransferases (ALT) greater than 1.5 the ULN
  3. Alkaline phosphatase greater than three times the ULN
  4. Albumin less than 3.0 mg/dL at the time of screening
Homozygous for low thiopurine S-methyl transferase (TPMT)
Uncontrolled depression (Hospital Anxiety and Depression [HAD] score greater than or equal to 15)
Known hypersensitivity to study medication
Any condition other than IPF that, in the opinion of the site PI, is likely to result in death in the 1 year after study entry
Any condition that, in the judgment of the PI, might cause participation in this study to be detrimental or makes the person a poor candidate for the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00650091

Locations

United States, Alabama
University of Alabama - Birmingham	Not yet recruiting
Birmingham, Alabama, United States, 35294
Contact: Tonja Meadows, RN 205-934-7557 tmeadows@uab.edu
Principal Investigator: Mitch Olman, MD
Sub-Investigator: Joao deAndrade, MD
United States, California
University of California - Los Angeles	Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Eileen Callahan, RN 310-794-2466 ecallahan@mednet.ucla.edu
Principal Investigator: David Zisman, MD
University of California - San Francisco	Not yet recruiting
San Francisco, California, United States, 94110
Contact: Renee Jeffrey, RN 415-476-5034 renee.jeffrey@ucsf.edu
Principal Investigator: Talmadge King, MD
Sub-Investigator: Harold Collard, MD
Sub-Investigator: Harold Chapman, MD
Sub-Investigator: Jeffrey Golden, MD
Sub-Investigator: Laura Koth, MD
Sub-Investigator: Paul Wolters, MD
United States, Colorado
National Jewish Medical and Research Center	Not yet recruiting
Denver, Colorado, United States, 80206
Contact: Dolly Kervitsky, RN 303-398-1621 kervitskyd@njc.org
Principal Investigator: Kevin Brown, MD
Sub-Investigator: Marvin Schwarz, MD
Sub-Investigator: Steven Frankel, MD
Sub-Investigator: Gregory Cosgrove, MD
United States, Georgia
Emory University	Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Tamra Perez, RN 404-727-6821 tamra.perez@emoryhealthcare.org
Principal Investigator: Jesse Roman, MD
Sub-Investigator: Rafael Perez, MD
United States, Illinois
University of Chicago	Recruiting
Chicago, Illinois, United States, 60637
Contact: Cathy Brown, RN 773-834-7083 cbrown@medicine.bsd.uchicago.edu
Principal Investigator: Imre Noth, MD
Sub-Investigator: Stephen White, MD
Sub-Investigator: Mary Strek, MD
United States, Louisiana
Tulane University	Recruiting
New Orleans, Louisiana, United States, 70118
Contact: Chodie Gabor, RN 504-988-2250 egabor@tulane.edu
Principal Investigator: Joseph Lasky, MD
United States, Michigan
University of Michigan	Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Debra Dahlgren, RN 734-936-8917 ddahlgre@med.umich.edu
Principal Investigator: Fernando Martinez, MD
Sub-Investigator: Kevin Flaherty, MD
Sub-Investigator: Galen Toews, MD
Sub-Investigator: MeiLan Han, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Kathleen Mieras 507-284-9187 mieras.kathleen@mayo.edu
Principal Investigator: Jay Ryu, MD
Sub-Investigator: James Utz, MD
Sub-Investigator: Andrew Limper, MD
United States, New York
Weill Medical College of Cornell University	Not yet recruiting
New York, New York, United States, 10021
Contact: Mei Wang, RN 212-746-5307 mew2001@med.cornell.edu
Principal Investigator: Robert Kaner, MD
United States, Tennessee
Vanderbilt University	Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Wendi Mason, RN 615-343-7068 wendi.mason@vanderbilt.edu
Principal Investigator: James Loyd, MD
Sub-Investigator: William Lawson, MD
Sub-Investigator: Lisa Lancaster, MD
United States, Washington
University of Washington	Not yet recruiting
Seattle, Washington, United States, 98165
Contact: Margaret Snyder, RN 206-685-4191 snyderp@u.washington.edu
Principal Investigator: Ganesh Raghu, MD

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:	Gary Hunninghake, MD	University of Iowa
Principal Investigator:	Kevin Brown, MD	National Jewish Health
Principal Investigator:	Rob Kaner, MD	Weill Medical College at Cornell University
Principal Investigator:	Talmadge King, MD	University of California, San Francisco
Principal Investigator:	Joe Lasky, MD	Tulane University School of Medicine
Principal Investigator:	James Loyd, MD	Vanderbilt University
Principal Investigator:	Fernando Martinez, MD	University of Michigan
Principal Investigator:	Imre Noth, MD	University of Chicago
Principal Investigator:	Ganesh Raghu, MD	University of Washington
Principal Investigator:	Jesse Roman, MD	Emory University
Principal Investigator:	Jay Ryu, MD	Mayo Clinic
Principal Investigator:	David Zisman, MD	University of California, Los Angeles
Principal Investigator:	Kevin Anstrom, PhD	Duke University
Study Director:	Herbert Reynolds, MD	National Heart, Lung, and Blood Institute (NHLBI)

More Information

Additional Information:

Click here for the IPFnet Web site. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Duke Clinical Research Institute ( Kevin J. Anstrom, Principal Investigator, DCC )
Study ID Numbers:	506, U10 HL080413-03, PANTHER001
Study First Received:	March 28, 2008
Last Updated:	November 24, 2009
ClinicalTrials.gov Identifier:	NCT00650091 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Idiopathic Pulmonary Fibrosis
Prednisone
Azathioprine
NAC
N-acetylcysteine

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Respiratory System Agents
Prednisone
Anti-Infective Agents
Antioxidants
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Fibrosis
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Pulmonary Fibrosis

Azathioprine
Pathologic Processes
Respiratory Tract Diseases
Therapeutic Uses
Free Radical Scavengers
Acetylcysteine
Antidotes
Lung Diseases, Interstitial
Antineoplastic Agents, Hormonal
Glucocorticoids
Immunosuppressive Agents
Antiviral Agents
Protective Agents
Pharmacologic Actions
Expectorants

ClinicalTrials.gov processed this record on February 08, 2010