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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00650091
First received: March 28, 2008
Last updated: May 27, 2015
Last verified: February 2015
  Purpose

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.


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:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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.


Enrollment: 264
Study Start Date: October 2009
Study Completion Date: January 2014
Primary Completion Date: October 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 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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 26 Study Locations
Sponsors and Collaborators
Duke University
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
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
  More Information

Additional Information:
No publications provided by Duke University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00650091     History of Changes
Other Study ID Numbers: Pro00020066, U10HL080413-03
Study First Received: March 28, 2008
Results First Received: July 31, 2014
Last Updated: May 27, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
Idiopathic Pulmonary Fibrosis
Prednisone
Azathioprine
NAC
N-acetylcysteine

Additional relevant MeSH terms:
Pulmonary Fibrosis
Lung Diseases
Respiratory Tract Diseases
Acetylcysteine
Azathioprine
N-monoacetylcystine
Prednisone
Anti-Infective Agents
Anti-Inflammatory Agents
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antioxidants
Antirheumatic Agents
Antiviral Agents
Expectorants
Free Radical Scavengers
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 29, 2015