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

NCT00650091 | Completed Phase 3 Results DMC

• 2 other identifiers: Pro00020066U10HL080413-03
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 26

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.

Conditions

Pulmonary Fibrosis

Keywords

Idiopathic Pulmonary Fibrosis; Prednisone; Azathioprine; NAC; N-acetylcysteine

Outcome Measures

Primary Outcomes (1)

• Overall Change in Forced Vital Capacity

  Change from Baseline in Forced Vital Capacity at 60 weeks (units in liters)

  Measured as the estimated change from baseline to Week 60

Secondary Outcomes (4)

• Disease Progression

  Measured at Week 60

• Acute Exacerbations

  Measured at Week 60

• Respiratory Infections

  Measured at Week 60

• Number of Participants With Maintained Forced Vital Capacity Response

  Measured at Week 60

Study Arms (2)

1

ACTIVE COMPARATOR

Participants will receive N-acetylcysteine (NAC) for 60 weeks.

Drug: N-acetylcysteine (NAC)

2

PLACEBO COMPARATOR

Participants will receive placebo for 60 weeks.

Drug: Placebo

Interventions

N-acetylcysteine (NAC) DRUG

Participants will receive 600 mg of NAC three times a day.

1

Placebo DRUG

Participants will receive placebo each day.

2

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (26)

University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California - Los Angeles

Los Angeles, California, 90095, United States

Location

University of California - San Francisco

San Francisco, California, 94110, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Louisville

Louisville, Kentucky, 40425, United States

Location

Tulane University

New Orleans, Louisiana, 70118, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

St. Luke's Hospital

Chesterfield, Missouri, 63107, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Highland Hospital - University of Rochester Medical Center

Rochester, New York, 14620, United States

Location

Duke Universtiy

Durham, North Carolina, 27705, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah Health Research Center

Salt Lake City, Utah, 84108, United States

Location

University of Washington

Seattle, Washington, 98165, United States

Location

Related Publications (5)

• Allen RJ, Stockwell A, Oldham JM, Guillen-Guio B, Schwartz DA, Maher TM, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV; International IPF Genetics Consortium. Genome-wide association study across five cohorts identifies five novel loci associated with idiopathic pulmonary fibrosis. Thorax. 2022 Aug;77(8):829-833. doi: 10.1136/thoraxjnl-2021-218577. Epub 2022 Jun 10.

  PMID: 35688625 DERIVED

• Andrade J, Schwarz M, Collard HR, Gentry-Bumpass T, Colby T, Lynch D, Kaner RJ; IPFnet Investigators. The Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet): diagnostic and adjudication processes. Chest. 2015 Oct;148(4):1034-1042. doi: 10.1378/chest.14-2889.

  PMID: 26111071 DERIVED

• Durheim MT, Collard HR, Roberts RS, Brown KK, Flaherty KR, King TE Jr, Palmer SM, Raghu G, Snyder LD, Anstrom KJ, Martinez FJ; IPFnet investigators. Association of hospital admission and forced vital capacity endpoints with survival in patients with idiopathic pulmonary fibrosis: analysis of a pooled cohort from three clinical trials. Lancet Respir Med. 2015 May;3(5):388-96. doi: 10.1016/S2213-2600(15)00093-4. Epub 2015 Apr 15.

  PMID: 25890798 DERIVED

• Idiopathic Pulmonary Fibrosis Clinical Research Network; Martinez FJ, de Andrade JA, Anstrom KJ, King TE Jr, Raghu G. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2093-101. doi: 10.1056/NEJMoa1401739. Epub 2014 May 18.

  PMID: 24836309 DERIVED

• Idiopathic Pulmonary Fibrosis Clinical Research Network; Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012 May 24;366(21):1968-77. doi: 10.1056/NEJMoa1113354. Epub 2012 May 20.

  PMID: 22607134 DERIVED

Related Links

• Click here for the Idiopathic Pulmonary Fibrosis Clinical Research Network web site.
• Clinical Alert: Commonly used three-drug regimen for idiopathic pulmonary fibrosis found harmful

MeSH Terms

Conditions

Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Kevin J Anstrom
• Organization: Duke Clinical Research Institute

kevin.anstrom@duke.edu

919-668-8902

Study Officials

• Marvin I Schwarz, MD

  University of Colorado, Denver

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

• Gail Weinmann, MD

  National Heart, Lung, and Blood Institute (NHLBI)

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2008
• First Posted: April 1, 2008
• Study Start: October 1, 2009
• Primary Completion: October 1, 2013
• Study Completion: January 1, 2014
• Last Updated: June 2, 2015
• Results First Posted: June 2, 2015

Record last verified: 2015-02

Locations

US (26)