Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in Patients With IPF (PANTHER-IPF)
Idiopathic pulmonary fibrosis (IPF) is a long-term lung disease that affects an individual's ability to breathe. In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups — receiving a combination of prednisone, azathioprine, and NAC (combination therapy), NAC alone, or placebo — in a 1:1:1 ratio.
|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|
- Overall Change in Forced Vital Capacity [ Time Frame: Measured as the estimated change from baseline to Week 60 ] [ Designated as safety issue: No ]Change from Baseline in Forced Vital Capacity at 60 weeks (units in liters)
- Disease Progression [ Time Frame: Measured at Week 60 ] [ Designated as safety issue: No ]
The time-to-death or a 10% decline in FVC will be defined as the time-to-disease progression.
The 10% decline in FVC from enrollment must be confirmed on 2 consecutive visits no less than 6 weeks apart. For subjects with 2 consecutive visits with a 10% decline in FVC, the time-to-disease progression will be defined as the time interval between enrollment and the initial visit with a 10% FVC decline.
- Acute Exacerbations [ Time Frame: Measured at Week 60 ] [ Designated as safety issue: No ]
The following 3 criteria will define acute exacerbations in subjects with acute worsening of their respiratory conditions:
1. Clinical (all of the following required): A) Unexplained worsening of dyspnea or cough within 30 days, triggering unscheduled medical care (e.g., emergency room, clinic, study visit, hospitalization). B) No clinical suspicion or overt evidence of cardiac event, pulmonary embolism, or deep venous thrombosis to explain acute worsening of dyspnea. C) No pneumothorax.
- Respiratory Infections [ Time Frame: Measured at Week 60 ] [ Designated as safety issue: No ]
- Number of Participants With Maintained Forced Vital Capacity Response [ Time Frame: Measured at Week 60 ] [ Designated as safety issue: No ]Maintained forced vital capacity response was a binary variable taking on a value of 1 for participants with higher FVC % predicted at week 60 compared to baseline.
|Study Start Date:||October 2009|
|Study Completion Date:||January 2014|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
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.
Participants will receive placebo each day.
IPF is a disease with widespread and permanent scarring of lung tissue which eventually results in death. Individuals with IPF may experience breathing difficulties, cough, chest pain, and a decreased exercise capacity. Although the cause of IPF is unknown, it may be a result of an inflammatory response to an unknown substance. 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.
In the initial double-blind, placebo-controlled trial, subjects who have idiopathic pulmonary fibrosis with mild-to-moderate impairment in pulmonary function are randomly assigned to receive a three-drug regimen of prednisone, azathioprine, and acetylcysteine; acetylcysteine alone; or placebo.
After safety concerns were identified by the data and safety monitoring board, the three-drug regimen was stopped by the National Heart, Lung, and Blood Institute (NHLBI) on October 14, 2011, and a clinical alert was issued. After a brief period of interruption for modification of the protocol and approval by the institutional review boards, patients continued to be recruited for the acetylcysteine group and the placebo group and were followed for the pre-specified duration of 60 weeks.
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, and questionnaires to assess health status, breathing, and quality of life. Participants will record medication usage and symptoms in a daily diary.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00650091
Show 26 Study Locations
|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|
|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|