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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00650091
First Posted: April 1, 2008
Last Update Posted: June 2, 2015
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.
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Duke University
Results First Submitted: July 31, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Pulmonary Fibrosis
Interventions: Drug: N-acetylcysteine (NAC)
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Initial Study Design: Subjects are randomly assigned to receive a three-drug regimen of prednisone, azathioprine, and acetylcysteine; acetylcysteine alone; or placebo.

Amended Study Design: The three-drug regimen was removed from the protocol due to safety concerns on 10/14/2011. Subjects are randomly assigned to acetylcysteine or placebo.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants in the Pred/AZA/NAC group were discontinued and not re-randomized in the amended study.

Reporting Groups
  Description
N-Acetylcysteine

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

N-acetylcysteine (NAC): Participants will receive 600 mg of NAC three times a day.

Placebo

Participants will receive placebo for 60 weeks.

Placebo: Participants will receive placebo each day.

Pred/AZA/NAC

The prednisone dose was started at 0.5 mg per kilo- gram of ideal body weight and was tapered to 0.15 mg per kilogram during a period of 25 weeks.

The azathioprine dose (maximum, 150 mg per day) was based on the patient’s ideal weight, concurrent use of allopurinol, and thiopurine methyl-transferase (TPMT) activity. NAC was prescribed at 600 mg orally three times a day.


Participant Flow for 2 periods

Period 1:   Initial Study Design - Interim Analysis
    N-Acetylcysteine   Placebo   Pred/AZA/NAC
STARTED   81   78   77 
COMPLETED   81   78   77 
NOT COMPLETED   0   0   0 

Period 2:   Amended Study Design
    N-Acetylcysteine   Placebo   Pred/AZA/NAC
STARTED   133   131   0 [1] 
COMPLETED   110   111   0 
NOT COMPLETED   23   20   0 
Withdrawal by Subject                12                11                0 
Physician Decision                5                0                0 
Adverse Event                1                4                0 
Lung transplantation                4                2                0 
Not specified                1                3                0 
[1] Study Drug was discontinued for all subjects due to safety concerns.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
N-Acetylcysteine

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

N-acetylcysteine (NAC): Participants will receive 600 mg of NAC three times a day.

Placebo

Participants will receive placebo for 60 weeks.

Placebo: Participants will receive placebo each day.

Total Total of all reporting groups

Baseline Measures
   N-Acetylcysteine   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 133   131   264 
Age 
[Units: Years]
Mean (Standard Deviation)
 68.3  (6.4)   67.2  (8.2)   67.8  (8.3) 
Gender 
[Units: Participants]
     
Female   26   33   59 
Male   107   98   205 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Overall Change in Forced Vital Capacity   [ Time Frame: Measured as the estimated change from baseline to Week 60 ]

Measure Type Primary
Measure Title Overall Change in Forced Vital Capacity
Measure Description Change from Baseline in Forced Vital Capacity at 60 weeks (units in liters)
Time Frame Measured as the estimated change from baseline to Week 60  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis population includes participants from the amended study design only.

Reporting Groups
  Description
N-Acetylcysteine

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

N-acetylcysteine (NAC): Participants will receive 600 mg of NAC three times a day.

Placebo

Participants will receive placebo for 60 weeks.

Placebo: Participants will receive placebo each day.


Measured Values
   N-Acetylcysteine   Placebo 
Participants Analyzed 
[Units: Participants]
 133   131 
Overall Change in Forced Vital Capacity 
[Units: Liters]
Mean (95% Confidence Interval)
 -0.18 
 (-0.23 to -0.12) 
 -0.19 
 (-0.24 to -0.14) 

No statistical analysis provided for Overall Change in Forced Vital Capacity



2.  Secondary:   Disease Progression   [ Time Frame: Measured at Week 60 ]

Measure Type Secondary
Measure Title Disease Progression
Measure Description

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.

Time Frame Measured at Week 60  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis population includes participants from the amended study design only.

Reporting Groups
  Description
N-Acetylcysteine

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

N-acetylcysteine (NAC): Participants will receive 600 mg of NAC three times a day.

Placebo

Participants will receive placebo for 60 weeks.

Placebo: Participants will receive placebo each day.


Measured Values
   N-Acetylcysteine   Placebo 
Participants Analyzed 
[Units: Participants]
 133   131 
Disease Progression 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 27.1 
 (20.1 to 36.0) 
 26.5 
 (19.5 to 35.4) 

No statistical analysis provided for Disease Progression



3.  Secondary:   Acute Exacerbations   [ Time Frame: Measured at Week 60 ]

Measure Type Secondary
Measure Title Acute Exacerbations
Measure Description

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.

Time Frame Measured at Week 60  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis population includes participants from the amended study design only.

Reporting Groups
  Description
N-Acetylcysteine

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

N-acetylcysteine (NAC): Participants will receive 600 mg of NAC three times a day.

Placebo

Participants will receive placebo for 60 weeks.

Placebo: Participants will receive placebo each day.


Measured Values
   N-Acetylcysteine   Placebo 
Participants Analyzed 
[Units: Participants]
 133   131 
Acute Exacerbations 
[Units: Events]
 3   3 

No statistical analysis provided for Acute Exacerbations



4.  Secondary:   Respiratory Infections   [ Time Frame: Measured at Week 60 ]

Measure Type Secondary
Measure Title Respiratory Infections
Measure Description No text entered.
Time Frame Measured at Week 60  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis population includes participants from the amended study design only.

Reporting Groups
  Description
N-Acetylcysteine

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

N-acetylcysteine (NAC): Participants will receive 600 mg of NAC three times a day.

Placebo

Participants will receive placebo for 60 weeks.

Placebo: Participants will receive placebo each day.


Measured Values
   N-Acetylcysteine   Placebo 
Participants Analyzed 
[Units: Participants]
 133   131 
Respiratory Infections 
[Units: Events]
 6   6 

No statistical analysis provided for Respiratory Infections



5.  Secondary:   Number of Participants With Maintained Forced Vital Capacity Response   [ Time Frame: Measured at Week 60 ]

Measure Type Secondary
Measure Title Number of Participants With Maintained Forced Vital Capacity Response
Measure Description 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.
Time Frame Measured at Week 60  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis population includes participants from the amended study design only.

Reporting Groups
  Description
N-Acetylcysteine

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

N-acetylcysteine (NAC): Participants will receive 600 mg of NAC three times a day.

Placebo

Participants will receive placebo for 60 weeks.

Placebo: Participants will receive placebo each day.


Measured Values
   N-Acetylcysteine   Placebo 
Participants Analyzed 
[Units: Participants]
 133   131 
Number of Participants With Maintained Forced Vital Capacity Response 
[Units: Participants]
 29   35 

No statistical analysis provided for Number of Participants With Maintained Forced Vital Capacity Response



6.  Post-Hoc:   Change in Forced Vital Capacity   [ Time Frame: Baseline, 15, 30, 45, 60 week ]

Measure Type Post-Hoc
Measure Title Change in Forced Vital Capacity
Measure Description Change from Baseline in Forced Vital Capacity at 15, 30, 45, and 60 weeks (units in liters)
Time Frame Baseline, 15, 30, 45, 60 week  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis population includes participants from the amended study design only.

Reporting Groups
  Description
N-Acetylcysteine

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

N-acetylcysteine (NAC): Participants will receive 600 mg of NAC three times a day.

Placebo

Participants will receive placebo for 60 weeks.

Placebo: Participants will receive placebo each day.


Measured Values
   N-Acetylcysteine   Placebo 
Participants Analyzed 
[Units: Participants]
 133   131 
Change in Forced Vital Capacity 
[Units: Liters]
Mean (Standard Deviation)
   
15 week   -0.07  (0.19)   -0.04  (0.19) 
30 week   -0.07  (0.20)   -0.08  (0.25) 
45 week   -0.15  (0.25)   -0.15  (0.30) 
60 week   -0.16  (0.26)   -0.15  (0.30) 

No statistical analysis provided for Change in Forced Vital Capacity




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Kevin J Anstrom
Organization: Duke Clinical Research Institute
phone: 919-668-8902
e-mail: kevin.anstrom@duke.edu


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 ( U.S. NIH Grant/Contract )
First Submitted: March 28, 2008
First Posted: April 1, 2008
Results First Submitted: July 31, 2014
Results First Posted: June 2, 2015
Last Update Posted: June 2, 2015