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Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in Patients With IPF (PANTHER-IPF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00650091
Recruitment Status : Completed
First Posted : April 1, 2008
Results First Posted : June 2, 2015
Last Update Posted : June 2, 2015
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE March 28, 2008
First Posted Date  ICMJE April 1, 2008
Results First Submitted Date  ICMJE July 31, 2014
Results First Posted Date  ICMJE June 2, 2015
Last Update Posted Date June 2, 2015
Study Start Date  ICMJE October 2009
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2015)
Overall Change in Forced Vital Capacity [ Time Frame: Measured as the estimated change from baseline to Week 60 ]
Change from Baseline in Forced Vital Capacity at 60 weeks (units in liters)
Original Primary Outcome Measures  ICMJE
 (submitted: March 28, 2008)
Change in serial forced vital capacity [ Time Frame: Measured at Week 60 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2015)
  • Disease Progression [ Time Frame: Measured at Week 60 ]
    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 ]
    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 ]
  • Number of Participants With Maintained Forced Vital Capacity Response [ Time Frame: Measured at Week 60 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2008)
  • Time to disease progression [ Time Frame: Measured at Week 60 ]
  • Acute exacerbations [ Time Frame: Measured at Week 60 ]
  • Respiratory infections [ Time Frame: Measured at Week 60 ]
  • Maintained forced vital capacity response [ Time Frame: Measured at Week 60 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in Patients With IPF
Official Title  ICMJE Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in IPF
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Fibrosis
Intervention  ICMJE
  • Drug: N-acetylcysteine (NAC)
    Participants will receive 600 mg of NAC three times a day.
  • Drug: Placebo
    Participants will receive placebo each day.
Study Arms  ICMJE
  • Active Comparator: 1
    Participants will receive N-acetylcysteine (NAC) for 60 weeks.
    Intervention: Drug: N-acetylcysteine (NAC)
  • Placebo Comparator: 2
    Participants will receive placebo for 60 weeks.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 19, 2014)
Original Estimated Enrollment  ICMJE
 (submitted: March 28, 2008)
Actual Study Completion Date  ICMJE January 2014
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00650091
Other Study ID Numbers  ICMJE Pro00020066
U10HL080413-03 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Duke University
Original Responsible Party Kevin J. Anstrom, Principal Investigator, DCC, Duke Clinical Research Institute
Current Study Sponsor  ICMJE Duke University
Original Study Sponsor  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
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
PRS Account Duke University
Verification Date February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP