CAMEO: Canadian Methotrexate and Etanercept Outcome Study

This study has been completed.
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00654368
First received: April 3, 2008
Last updated: July 14, 2014
Last verified: July 2014
Results First Received: February 10, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Biological: Etanercept
Drug: Methotrexate

  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
First patient was enrolled 28 June 2008 and last patient was enrolled 07 November 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 258 participants were enrolled, of whom 205 were randomized after 6 months and 53 were not randomized.

Reporting Groups
  Description
Non-randomized Enrolled participants received treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) but discontinued prior to completing this 6 months of treatment.
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Participant Flow:   Overall Study
    Non-randomized     Etanercept Alone     Etanercept + Methotrexate  
STARTED     53     98     107  
COMPLETED     0     50     75  
NOT COMPLETED     53     48     32  
Ineligibility determined                 6                 0                 0  
Protocol deviation                 3                 2                 1  
Non-compliance                 2                 1                 2  
Withdrawal by Subject                 5                 2                 2  
Disease progression                 21                 31                 13  
Requirement for alternative therapy                 1                 1                 1  
Physician Decision                 0                 0                 2  
Death                 1                 0                 0  
Pregnancy                 0                 0                 2  
Other                 0                 2                 3  
Adverse Event                 14                 9                 6  



  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
Non-randomized Enrolled participants received treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) but discontinued prior to completing this 6 months of treatment.
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.
Total Total of all reporting groups

Baseline Measures
    Non-randomized     Etanercept Alone     Etanercept + Methotrexate     Total  
Number of Participants  
[units: participants]
  53     98     107     258  
Age  
[units: years]
Mean ± Standard Deviation
  56.2  ± 13.4     54.3  ± 11.9     54.4  ± 12.7     54.7  ± 12.5  
Gender  
[units: participants]
       
Female     41     72     84     197  
Male     12     26     23     61  
Race/Ethnicity, Customized  
[units: participants]
       
White or Caucasian     47     96     103     246  
Black or African American     2     1     0     3  
Hispanic or Latino     0     0     1     1  
Asian     2     0     0     2  
Native Hawaiian or other Pacific Islander     0     0     3     3  
Aborigine     1     0     0     1  
Other     1     1     0     2  
Duration of rheumatoid arthritis  
[units: participants]
       
< 2 years     11     23     23     57  
>= 2 years     42     75     84     201  
Reimbursement type  
[units: participants]
       
Private     23     48     55     126  
Public     16     33     37     86  
Combination/Other     14     17     15     46  
Disease Activity Score (DAS28-ESR) [1]
[units: participants]
       
<= 5.1     20     43     41     104  
> 5.1     33     55     66     154  
[1] The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28)   [ Time Frame: Month 6 (randomization) and Month 12 ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28)
Measure Description The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. In this study, the mean change in DAS28 scores from Month 6 to Month 12 was multiplied by a factor of -1, such that a negative change in DAS28 indicates worsening in disease activity.
Time Frame Month 6 (randomization) and Month 12  
Safety Issue No  

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.
The per protocol population defined as all randomized participants with DAS28 measurements both at the 6- and 12-month visit.

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  73     88  
Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28)  
[units: scores on a scale]
Least Squares Mean ± Standard Error
  -0.39  ± 0.11     0.02  ± 1.26  


Statistical Analysis 1 for Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28)
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Mean Difference [3] -0.41
95% Confidence Interval ( -0.75 to -0.06 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  If the lower bound of the one-sided 95% confidence interval (CI), defined below, exceeded the noninferiority margin of -0.6, then noninferiority was to be concluded.
[3] Other relevant estimation information:
  The 95% CI was calculated using the mean square error from an analysis of variance (ANOVA) fitted with effects for treatment and covariates of duration of disease, type of reimbursement, and 6 month DAS28.



2.  Secondary:   Disease Activity Score (DAS) 28 Response   [ Time Frame: Month 6, 12, 18 and 24 ]

3.  Secondary:   Change From Baseline in Disease Activity Score 28 (DAS28)   [ Time Frame: Baseline and Month 6, 12, 18 and 24 ]

4.  Secondary:   Drug Persistence   [ Time Frame: Month 6, 12, 18 and 24 ]

5.  Secondary:   Change From Baseline in Modified Total Sharp Score (mTSS)   [ Time Frame: Baseline, Month 12 and Month 24 ]

6.  Secondary:   Change From Baseline in Joint Erosion Score   [ Time Frame: Baseline, Month 12 and Month 24 ]

7.  Secondary:   Change From Baseline in Joint Space Narrowing   [ Time Frame: Baseline, Month 12 and Month 24 ]

8.  Secondary:   Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI)   [ Time Frame: Month 6, 12, 18 and 24 ]

9.  Secondary:   Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS)   [ Time Frame: Month 6, 12, 18 and 24 ]

10.  Secondary:   Change From Month 6 in Short Form 36 Health Survey (SF-36)   [ Time Frame: Month 6, 12, 18 and 24 ]

11.  Secondary:   Change From Month 6 in Work Productivity and Activity Impairment (WPAI)   [ Time Frame: Month 6, 12, 18 and 24 ]

12.  Secondary:   Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM)   [ Time Frame: Month 6, 12, 18 and 24 ]

13.  Secondary:   Number of Participants With Adverse Events (AEs)   [ Time Frame: 25 months ]


  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
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


No publications provided


Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00654368     History of Changes
Other Study ID Numbers: 20070301
Study First Received: April 3, 2008
Results First Received: February 10, 2014
Last Updated: July 14, 2014
Health Authority: Canada: Institutional Review Board