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 (Responsible Party):	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), at preventing the loss of lung function in people with IPF.

Condition	Intervention	Phase
Pulmonary Fibrosis	Drug: N-acetylcysteine (NAC) Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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 Acetylcysteine Azathioprine Sodium

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:	September 2013
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Participants will receive N-acetylcysteine (NAC) for 60 weeks.	Drug: N-acetylcysteine (NAC) Participants will receive 600 mg of NAC three times a day.
Placebo Comparator: 2 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, 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.

Eligibility

Ages Eligible for Study:	35 Years to 85 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
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

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Locations

United States, Alabama
University of Alabama - Birmingham	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	Recruiting
Los Angeles, California, United States, 90095
Contact: Eileen Callahan, RN 310-794-2466 ecallahan@mednet.ucla.edu
Principal Investigator: Joseph Lynch, MD
University of California - San Francisco	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	Recruiting
Denver, Colorado, United States, 80206
Contact: Carol Bair, RCP, CRC 303-398-1912 bairc@njhealth.org
Principal Investigator: Kevin Brown, MD
Sub-Investigator: Marvin Schwarz, MD
Sub-Investigator: Steven Frankel, MD
Sub-Investigator: Gregory Cosgrove, MD
United States, Connecticut
Yale University School of Medicine	Recruiting
New Haven, Connecticut, United States, 06520
Contact: Kathryn Engle, RN 203-785-7324 kathryn.engle@yale.edu
Principal Investigator: Danielle Antin-Ozerkis, MD
United States, Florida
University of Miami Miller School of Medicine	Recruiting
Miami, Florida, United States, 33136
Contact: Emmanuelle Simonet, RN 305-243-3728 esimonet@med.miami.edu
Principal Investigator: Marilyn Glassberg, MD
United States, Illinois
University of Chicago	Recruiting
Chicago, Illinois, United States, 60637
Contact: Spring Maleckar, RN 773-834-4053 smalecka@medicine.bsd.uchicago.edu
Principal Investigator: Imre Noth, MD
Sub-Investigator: Stephen White, MD
Sub-Investigator: Mary Strek, MD
United States, Kentucky
University of Louisville	Recruiting
Louisville, Kentucky, United States, 40425
Contact: Tamra Perez, RN 502-852-1358 tamra.perez@louisville.edu
Principal Investigator: Jesse Roman, MD
Sub-Investigator: Rafael Perez, MD
United States, Louisiana
Tulane University	Recruiting
New Orleans, Louisiana, United States, 70118
Contact: Sandy Ditta, RN 504-988-4040 sditta@tulane.edu
Principal Investigator: Joseph Lasky, MD
United States, Massachusetts
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Maureen Vey, RN 617-667-4708 mvey@bidmc.harvard.edu
Principal Investigator: Joseph Zibrak, MD
Sub-Investigator: Peter LaCamera, MD
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Pierre Debrosse 617-732-7420 pdebrosse@partners.org
Principal Investigator: Ivan O Rosas, MD
Sub-Investigator: Erin Morse, MD
Sub-Investigator: Hillary Goldberg, MD
Sub-Investigator: Paul Dellaripa, MD
United States, Michigan
University of Michigan	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, Missouri
St. Luke's Hospital	Recruiting
Chesterfield, Missouri, United States, 63107
Contact: Sue Merli, RN 314-576-4501 sue.merli@stlukes-stl.com
Principal Investigator: Neil Ettinger, MD
United States, New York
Weill Medical College of Cornell University	Recruiting
New York, New York, United States, 10021
Contact: Vanessa Monroy, RN 646-962-5568 vam2012@med.cornell.edu
Principal Investigator: Robert Kaner, MD
Mount Sinai Hospital	Recruiting
New York, New York, United States, 10029
Contact: Olivera Calukovic 212-241-0059 olivera.calukovic@mssm.edu
Principal Investigator: Maria Padilla, MD
Sub-Investigator: Adam Morgenthau, MD
Sub-Investigator: Alvin Teirstein, MD
Highland Hospital - University of Rochester Medical Center	Recruiting
Rochester, New York, United States, 14620
Contact: Elizabeth Lyda, RN 585-233-4358 elizabeth_lyda@urmc.rochester.edu
Principal Investigator: Michael Kallay, MD
United States, North Carolina
Duke Universtiy	Recruiting
Durham, North Carolina, United States, 27705
Contact: Melissa Westbrook, RN 919-668-8854 melissa.westbrook@duke.edu
Principal Investigator: Lake Morrison, MD
United States, Ohio
Cleveland Clinic	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Susan Lubell, RN 216-445-5872 lubells@ccf.org
Principal Investigator: Jeffrey Chapman, MD
United States, Pennsylvania
University of Pennsylvania Health System	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Susan Metzger, RN 215-662-3115 susan.metzger@uphs.upenn.edu
Principal Investigator: Milton Rossman, MD
Temple University	Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Gayle Jones 215-707-2687 gayle.jones@tuhs.temple.edu
Principal Investigator: Gerard Criner, MD
Sub-Investigator: Michael Jacobs, MD
United States, South Carolina
Medical University of South Carolina	Recruiting
Charleston, South Carolina, United States, 29425
Contact: Teresa Johnson, RN 843-732-0401 johnsotm@musc.edu
Principal Investigator: Steven Sahn, MD
United States, Tennessee
Vanderbilt University	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, Texas
University of Texas Southwestern Medical Center	Recruiting
Dallas, Texas, United States, 75390
Contact: Allison Johnson, RN 214-648-6702 allison.johnson@utsouthwestern.edu
Principal Investigator: John Fitzgerald, MD
United States, Utah
University of Utah Health Research Center	Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Laurie Brewster, RN 801-581-5811 laurie.brewster@hsc.utah.edu
Principal Investigator: Mary Beth Scholand, MD
United States, Washington
University of Washington	Recruiting
Seattle, Washington, United States, 98165
Contact: Trish Berry-Bell, RN 206-598-6871 tbb@u.washington.edu
Principal Investigator: Ganesh Raghu, MD

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:	Marvin I Schwarz, MD	University of Colorado, Denver
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:	John Belperio, MD	University of California, Los Angeles
Principal Investigator:	Kevin Anstrom, PhD	Duke University
Study Director:	Gail Weinmann, MD	National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator:	Jeffrey Chapman, MD	The Cleveland Clinic
Principal Investigator:	Lake Morrison, MD	Duke University
Principal Investigator:	Michael Kallay, MD	Highland Hospital
Principal Investigator:	Steven Sahn, MD	Medical University of South Carolina
Principal Investigator:	Marilyn Glassberg, MD	University of Miami
Principal Investigator:	Milton Rossman, MD	University of Pennsylvania
Principal Investigator:	John Fitzgerald, MD	University of Texas
Principal Investigator:	Mary Beth Scholand, MD	University of Utah
Principal Investigator:	Neil Ettinger, MD	St Luke's Hospital
Principal Investigator:	Danielle Antin-Ozerkis, MD	Yale University
Principal Investigator:	Joao deAndrade, MD	University of Alabama at Birmingham
Principal Investigator:	Ivan Rosas, MD	Brigham and Women's
Principal Investigator:	Joseph Zibrak, MD	Beth Isreal-Deaconess
Principal Investigator:	Gerald Criner, MD	Temple University
Principal Investigator:	Maria Padilla, MD	Mount Sinai Hospital, New York

Responsible Party:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00650091 History of Changes
Other Study ID Numbers:	506, U10 HL080413-03, PANTHER001
Study First Received:	March 28, 2008
Last Updated:	January 23, 2012
Health Authority:	United States: Food and Drug Administration