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Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II) (SLSII)

This study has been completed.
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Hoffmann-La Roche
Information provided by (Responsible Party):
Michael Roth, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00883129
First received: April 16, 2009
Last updated: February 6, 2017
Last verified: February 2017
Results First Received: November 6, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Participant, Care Provider, Investigator, Outcomes Assessor;   Primary Purpose: Treatment
Conditions: Scleroderma
Interstitial Lung Disease
Interventions: Drug: Mycophenolate mofetil
Drug: Cyclophosphamide
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment was carried out between September 28, 2009, and January 14, 2013, at 14 University Medical Centers within the United States.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Mycophenolate Arm

Participants treated with oral mycophenolate mofetil for 2 years.

Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated

Cyclophosphamide Arm

Participants treated with oral cyclophosphamide for 1 year, followed by placebo for 1 year.

Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated

Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.


Participant Flow:   Overall Study
    Mycophenolate Arm   Cyclophosphamide Arm
STARTED   69   73 
COMPLETED   49 [1]   37 [2] 
NOT COMPLETED   20   36 
Adverse Event                7                15 
Withdrawal by Subject                8                9 
Non-compliance                3                6 
Lost to Follow-up                1                2 
Death                1                2 
Defined Treatment Failure                0                2 
[1] 53 subjects provided a 24 month outcome, 4 of whom had prematurely withdrawn from drug treatment.
[2] 53 subjects provided a 24 month outcome, 16 of whom had prematurely withdrawn from drug treatment.



  Baseline Characteristics
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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
Mycophenolate Arm

Participants will receive oral mycophenolate mofetil for 2 years.

Mycophenolate mofetil: 24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated

Cyclophosphamide Arm

Participants will receive oral cyclophosphamide for 1 year, followed by placebo for 1 year.

Cyclophosphamide: 12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated

Placebo: 12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.

Total Total of all reporting groups

Baseline Measures
   Mycophenolate Arm   Cyclophosphamide Arm   Total 
Overall Participants Analyzed 
[Units: Participants]
 69   73   142 
Age 
[Units: Years]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   52.6  (9.7)   52.0  (9.8)   52.3  (9.7) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
Female      48  69.6%      57  78.1%      105  73.9% 
Male      21  30.4%      16  21.9%      37  26.1% 
Duration of scleroderma [1] 
[Units: Years]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 67   72   139 
   2.6  (1.7)   2.5  (1.8)   2.6  (1.8) 
[1] Only participants with available data included
Limited cutaneous scleroderma 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   26   33   59 
Diffuse cutaneous scleroderma 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   43   40   83 
modified-Rodnan Skin Score [1] 
[Units: Score]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   15.3  (10.4)   14.0  (10.6)   14.7  (10.5) 
[1] Skin score may range 0-51, with higher scores indicating more severe thickening
FVC %-predicted 
[Units: Percent of predicted normal value]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   66.5  (9.1)   66.5  (8.3)   66.5  (9.9) 
FEV1/FVC %-predicted 
[Units: Percent of predicted normal value]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   81.0  (5.5)   83.3  (5.6)   82.6  (5.6) 
Total Lung Capacity 
[Units: Percent of predicted normal value]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   66.3  (10.0)   65.5  (12.0)   65.8  (11.1) 
Single-Breath Diffusing Capacity 
[Units: Percent of predicted normal value]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   60.9  (11.8)   61.0  (13.7)   60.9  (12.8) 
Mahler Dyspnea Index, mean focal score [1] [2] 
[Units: Score]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 65   68   133 
   7.3  (2.1)   7.1  (2.3)   7.2  (2.2) 
[1] Scores range 0-12, with lower scores indicating worse dyspnea
[2] Only participants with available data included
SF-36 Physical component [1] 
[Units: Score]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   36.0  (10.0)   35.6  (9.8)   35.8  (9.9) 
[1] Score range 0-100, with lower scores indicating worse health status
SF-36 Mental component [1] 
[Units: Score]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   49.1  (7.9)   49.8  (10.0)   49.4  (9.0) 
[1] Score range 0-100, with lower scores indicating worse health status
HAQ disability index [1] 
[Units: Score]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 69   73   142 
   0.7  (0.6)   0.7  (0.7)   0.7  (0.7) 
[1] Score range 0-3, with higher scores indicating greater disability
Quantitative extent of lung fibrosis on HRCT, for whole lung [1] [2] 
[Units: Score]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 66   71   137 
   8.3  (6.9)   8.9  (7.0)   8.6  (6.9) 
[1] Score range 0 to 100, with higher score indicating greater lung involvement
[2] Only participants with available data included
Quantitative extent of lung fibrosis on HRCT, for lobe of maximum involvement [1] [2] 
[Units: Score]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 66   71   137 
   23.0  (20.2)   22.6  (19.3)   22.8  (19.6) 
[1] Score range 0 to 100, with higher score indicating greater lung involvement
[2] Only participants with available data included
Quantitative extent of total insterstitial lung disease on HRCT, for whole lung [1] [2] 
[Units: Score]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 66   71   137 
   27.2  (13.2)   31.6  (14.4)   29.5  (14.0) 
[1] Score range 0 to 100, with higher score indicating greater lung involvement
[2] Only participants with available data included
Quantitative extent of total insterstitial lung disease on HRCT, for lobe of maximum involvement [1] [2] 
[Units: Score]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 66   71   137 
   50.0  (20.9)   52.3  (19.9)   51.2  (20.3) 
[1] Score range 0 to 100, with higher score indicating greater lung involvement
[2] Only participants with available data included
ANA(+) [1] 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 63   71   134 
   61   66   127 
[1] Only participants with available data included
Topoisomerase-1(+) [1] 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 63   71   134 
   29   32   61 
[1] Only participants with available data included
RNA Polymerase(+) [1] 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 63   71   134 
   9   9   18 
[1] Only participants with available data included
Centromere(+) [1] 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 63   71   134 
   1   2   3 
[1] Only participants with available data included


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value   [ Time Frame: Measured at study Baseline and Months 3, 6, 12, 15, 18, 21, and 24 ]

2.  Secondary:   Total Lung Capacity (TLC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value   [ Time Frame: Measured at study entry and Months 6, 12, 18, and 24 ]

3.  Secondary:   Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value   [ Time Frame: Measured at study entry and Months 3, 6, 12, 15, 18, 21, and 24 ]

4.  Secondary:   Fibrosis Score, as Measured by Thoracic High Resolution Computerized Tomography (HRCT)   [ Time Frame: Measured at baseline and Month 24 ]

5.  Secondary:   Transitional Dyspnea Index Score   [ Time Frame: Measured at Months 6, 12, 18, and 24 ]

6.  Secondary:   Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI)   [ Time Frame: Measured at study entry and Months 3, 6, 9, 12, 15, 18, 21, and 24 ]

7.  Secondary:   Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS)   [ Time Frame: Measured at baseline and Months 3, 6, 9, 12, 15, 18, 21, and 24 ]

8.  Secondary:   Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death   [ Time Frame: Measured throughout the 2-year study ]

9.  Secondary:   Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure.   [ Time Frame: Continuous assessment from randomization to 24 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
While the rate of premature withdrawal from taking study drug was significant, this was anticipated in the study design and addressed by the sample size and the use of the mixed model statistical analysis.


  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: Donald P. Tashkin, M.D.
Organization: David Geffen School of Medicine at UCLA
phone: 310-825-5316
e-mail: dtashkin@mednet.ucla.edu


Publications of Results:

Other Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Michael Roth, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00883129     History of Changes
Other Study ID Numbers: 632
R01HL089901 ( US NIH Grant/Contract Award Number )
R01HL089758 ( US NIH Grant/Contract Award Number )
Study First Received: April 16, 2009
Results First Received: November 6, 2016
Last Updated: February 6, 2017