Phase 3
N=236
Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in Patients With IPF
Pulmonary Fibrosis
Bottom Line
View on ClinicalTrials.gov: NCT00650091 ↗Enrolled (actual)
236
Serious AEs
18.4%
Results posted
Jun 2015
Primary outcome: Primary: Overall Change in Forced Vital Capacity — -0.18; -0.19 liters
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- N-acetylcysteine (NAC) (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 35+ yrs
- Sex
- All
- Sponsor
- Duke University
- Primary completion
- Oct 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Change in Forced Vital Capacity |
-0.18; -0.19 | — |
| SECONDARY Disease Progression |
27.1; 26.5 | — |
| SECONDARY Acute Exacerbations |
3; 3 | — |
| SECONDARY Respiratory Infections |
6; 6 | — |
| SECONDARY Number of Participants With Maintained Forced Vital Capacity Response |
29; 35 | — |
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.
Eligibility 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:
- Creatinine greater than twice the upper limit of normal (ULN)
- Hematology outside of specified limits
- White blood cells less than 3,500/mm3
- Hematocrit less than 25% or greater than 59%
- Platelets less than 100, 000 mm3 at the time of screening
- Any of the following liver function test criteria above specified limits
- Total bilirubin greater than twice the ULN
- Aspartate (AST) or alanine aminotransferases (ALT) greater than 1.5 the ULN
- Alkaline phosphatase greater than three times the ULN
- 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
Data sourced from ClinicalTrials.gov (NCT00650091). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.