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

Condition(s) targeted: Pulmonary Fibrosis

Intervention: N-acetylcysteine (NAC) (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

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

Official(s) and/or principal investigator(s):
Marvin I Schwarz, MD, Study Chair, Affiliation: University of Colorado, Denver
Kevin Brown, MD, Principal Investigator, Affiliation: National Jewish Health
Rob Kaner, MD, Principal Investigator, Affiliation: Weill Medical College at Cornell University
Talmadge King, MD, Principal Investigator, Affiliation: University of California, San Francisco
Joe Lasky, MD, Principal Investigator, Affiliation: Tulane University School of Medicine
James Loyd, MD, Principal Investigator, Affiliation: Vanderbilt University
Fernando Martinez, MD, Principal Investigator, Affiliation: University of Michigan
Imre Noth, MD, Principal Investigator, Affiliation: University of Chicago
Ganesh Raghu, MD, Principal Investigator, Affiliation: University of Washington
Jesse Roman, MD, Principal Investigator, Affiliation: Emory University
Jay Ryu, MD, Principal Investigator, Affiliation: Mayo Clinic
John Belperio, MD, Principal Investigator, Affiliation: University of California, Los Angeles
Kevin Anstrom, PhD, Principal Investigator, Affiliation: Duke University
Gail Weinmann, MD, Study Director, Affiliation: National Heart, Lung, and Blood Institute (NHLBI)
Jeffrey Chapman, MD, Principal Investigator, Affiliation: The Cleveland Clinic
Lake Morrison, MD, Principal Investigator, Affiliation: Duke University
Michael Kallay, MD, Principal Investigator, Affiliation: Highland Hospital
Steven Sahn, MD, Principal Investigator, Affiliation: Medical University of South Carolina
Marilyn Glassberg, MD, Principal Investigator, Affiliation: University of Miami
Milton Rossman, MD, Principal Investigator, Affiliation: University of Pennsylvania
John Fitzgerald, MD, Principal Investigator, Affiliation: University of Texas
Mary Beth Scholand, MD, Principal Investigator, Affiliation: University of Utah
Neil Ettinger, MD, Principal Investigator, Affiliation: St Luke's Hospital
Danielle Antin-Ozerkis, MD, Principal Investigator, Affiliation: Yale University
Joao deAndrade, MD, Principal Investigator, Affiliation: University of Alabama at Birmingham
Ivan Rosas, MD, Principal Investigator, Affiliation: Brigham and Women's
Joseph Zibrak, MD, Principal Investigator, Affiliation: Beth Isreal-Deaconess
Gerald Criner, MD, Principal Investigator, Affiliation: Temple University
Maria Padilla, MD, Principal Investigator, Affiliation: Mount Sinai Hospital, New York

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), at preventing the loss of lung function in people with IPF.

Official title: Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in IPF

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

Primary outcome: Change in serial forced vital capacity

Secondary outcome:

Time to disease progression

Acute exacerbations

Respiratory infections

Maintained forced vital capacity response

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, and no approved treatment for the disease. NAC, an antioxidant that is effective at loosening up mucus that forms in the lungs, may improve lung function. The purpose of this study is to evaluate the effectiveness of NAC 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 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.

Minimum age: 35 Years. Maximum age: 85 Years. Gender(s): Both.

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

- 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

University of Alabama - Birmingham, Birmingham, Alabama 35294, United States; Recruiting
Tonja Meadows, RN, Phone: 205-934-7557, Email: tmeadows@uab.edu
Mitch Olman, MD, Principal Investigator
Joao deAndrade, MD, Sub-Investigator

University of California - Los Angeles, Los Angeles, California 90095, United States; Recruiting
Eileen Callahan, RN, Phone: 310-794-2466, Email: ecallahan@mednet.ucla.edu
Joseph Lynch, MD, Principal Investigator

University of California - San Francisco, San Francisco, California 94110, United States; Recruiting
Renee Jeffrey, RN, Phone: 415-476-5034, Email: renee.jeffrey@ucsf.edu
Talmadge King, MD, Principal Investigator
Harold Collard, MD, Sub-Investigator
Harold Chapman, MD, Sub-Investigator
Jeffrey Golden, MD, Sub-Investigator
Laura Koth, MD, Sub-Investigator
Paul Wolters, MD, Sub-Investigator

National Jewish Medical and Research Center, Denver, Colorado 80206, United States; Recruiting
Carol Bair, RCP, CRC, Phone: 303-398-1912, Email: bairc@njhealth.org
Kevin Brown, MD, Principal Investigator
Marvin Schwarz, MD, Sub-Investigator
Steven Frankel, MD, Sub-Investigator
Gregory Cosgrove, MD, Sub-Investigator

Yale University School of Medicine, New Haven, Connecticut 06520, United States; Recruiting
Kathryn Engle, RN, Phone: 203-785-7324, Email: kathryn.engle@yale.edu
Danielle Antin-Ozerkis, MD, Principal Investigator

University of Miami Miller School of Medicine, Miami, Florida 33136, United States; Recruiting
Emmanuelle Simonet, RN, Phone: 305-243-3728, Email: esimonet@med.miami.edu
Marilyn Glassberg, MD, Principal Investigator

University of Chicago, Chicago, Illinois 60637, United States; Recruiting
Spring Maleckar, RN, Phone: 773-834-4053, Email: smalecka@medicine.bsd.uchicago.edu
Imre Noth, MD, Principal Investigator
Stephen White, MD, Sub-Investigator
Mary Strek, MD, Sub-Investigator

University of Louisville, Louisville, Kentucky 40425, United States; Recruiting
Tamra Perez, RN, Phone: 502-852-1358, Email: tamra.perez@louisville.edu
Jesse Roman, MD, Principal Investigator
Rafael Perez, MD, Sub-Investigator

Tulane University, New Orleans, Louisiana 70118, United States; Recruiting
Sandy Ditta, RN, Phone: 504-988-4040, Email: sditta@tulane.edu
Joseph Lasky, MD, Principal Investigator

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States; Recruiting
Maureen Vey, RN, Phone: 617-667-4708, Email: mvey@bidmc.harvard.edu
Joseph Zibrak, MD, Principal Investigator
Peter LaCamera, MD, Sub-Investigator

Brigham and Women's Hospital, Boston, Massachusetts 02115, United States; Recruiting
Pierre Debrosse, Phone: 617-732-7420, Email: pdebrosse@partners.org
Ivan O Rosas, MD, Principal Investigator
Erin Morse, MD, Sub-Investigator
Hillary Goldberg, MD, Sub-Investigator
Paul Dellaripa, MD, Sub-Investigator

University of Michigan, Ann Arbor, Michigan 48109, United States; Recruiting
Debra Dahlgren, RN, Phone: 734-936-8917, Email: ddahlgre@med.umich.edu
Fernando Martinez, MD, Principal Investigator
Kevin Flaherty, MD, Sub-Investigator
Galen Toews, MD, Sub-Investigator
MeiLan Han, MD, Sub-Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Kathleen Mieras, Phone: 507-284-9187, Email: mieras.kathleen@mayo.edu
Jay Ryu, MD, Principal Investigator
James Utz, MD, Sub-Investigator
Andrew Limper, MD, Sub-Investigator

St. Luke's Hospital, Chesterfield, Missouri 63107, United States; Recruiting
Sue Merli, RN, Phone: 314-576-4501, Email: sue.merli@stlukes-stl.com
Neil Ettinger, MD, Principal Investigator

Weill Medical College of Cornell University, New York, New York 10021, United States; Recruiting
Vanessa Monroy, RN, Phone: 646-962-5568, Email: vam2012@med.cornell.edu
Robert Kaner, MD, Principal Investigator

Mount Sinai Hospital, New York, New York 10029, United States; Recruiting
Olivera Calukovic, Phone: 212-241-0059, Email: olivera.calukovic@mssm.edu
Maria Padilla, MD, Principal Investigator
Adam Morgenthau, MD, Sub-Investigator
Alvin Teirstein, MD, Sub-Investigator

Highland Hospital - University of Rochester Medical Center, Rochester, New York 14620, United States; Recruiting
Elizabeth Lyda, RN, Phone: 585-233-4358, Email: elizabeth_lyda@urmc.rochester.edu
Michael Kallay, MD, Principal Investigator

Duke Universtiy, Durham, North Carolina 27705, United States; Recruiting
Melissa Westbrook, RN, Phone: 919-668-8854, Email: melissa.westbrook@duke.edu
Lake Morrison, MD, Principal Investigator

Cleveland Clinic, Cleveland, Ohio 44195, United States; Recruiting
Susan Lubell, RN, Phone: 216-445-5872, Email: lubells@ccf.org
Jeffrey Chapman, MD, Principal Investigator

University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, United States; Recruiting
Susan Metzger, RN, Phone: 215-662-3115, Email: susan.metzger@uphs.upenn.edu
Milton Rossman, MD, Principal Investigator

Temple University, Philadelphia, Pennsylvania 19140, United States; Recruiting
Gayle Jones, Phone: 215-707-2687, Email: gayle.jones@tuhs.temple.edu
Gerard Criner, MD, Principal Investigator
Michael Jacobs, MD, Sub-Investigator

Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting
Teresa Johnson, RN, Phone: 843-732-0401, Email: johnsotm@musc.edu
Steven Sahn, MD, Principal Investigator

Vanderbilt University, Nashville, Tennessee 37232, United States; Recruiting
Wendi Mason, RN, Phone: 615-343-7068, Email: wendi.mason@vanderbilt.edu
James Loyd, MD, Principal Investigator
William Lawson, MD, Sub-Investigator
Lisa Lancaster, MD, Sub-Investigator

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States; Recruiting
Allison Johnson, RN, Phone: 214-648-6702, Email: allison.johnson@utsouthwestern.edu
John Fitzgerald, MD, Principal Investigator

University of Utah Health Research Center, Salt Lake City, Utah 84108, United States; Recruiting
Laurie Brewster, RN, Phone: 801-581-5811, Email: laurie.brewster@hsc.utah.edu
Mary Beth Scholand, MD, Principal Investigator

University of Washington, Seattle, Washington 98165, United States; Recruiting
Trish Berry-Bell, RN, Phone: 206-598-6871, Email: tbb@u.washington.edu
Ganesh Raghu, MD, Principal Investigator

Click here for the IPFnet Web site.

Starting date: October 2009
Last updated: January 23, 2012