Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT00195494
First received: September 13, 2005
Last updated: August 1, 2012
Last verified: August 2012
Results First Received: March 31, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: Etanercept
Drug: Methotrexate
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
Participants were recruited worldwide from November 2004 to February 2006.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomly assigned equally to 1 of 4 blinded treatment groups: Group (G) 1a received the combination of etanercept (E) and methotrexate (M) in year Y1 and Y2. G1b received the combination of E and M in Y1 and E alone in Y2. G2a received M alone in Y1 and the combination of E and M in Y2. G2b received M alone in Y1 and Y2.

Reporting Groups
  Description
Year 1 E+M / Year 2 E+M

Following a blinded transition from year one- Etanercept injection- two injections 25 mg weekly (given at the same time at different sites)+ oral Methotrexate capsules weekly (same day as injection).

Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.

Year 1 M / Year 2 E+M

Following a blinded transition from year one- Etanercept two injections 25 mg weekly (given at the same time at different sites) + oral Methotrexate capsules weekly (same day as injection).

Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.

Year 1 E+M / Year 2 E Following a blinded transition from year one-Etanercept two injections 25 mg weekly (given at the same time at different sites).
Year 1 M / Year 2 M

Following a blinded transition from year one- Methotrexate dose consistent with the ending dose of year one (usually 20 mgs).

No reduction of MTX dose is permitted in year two.

Year 1 M+Placebo

Oral Methotrexate capsules once weekly + two injections of placebo given at the same time at different sites.

MTX dose is a forced titration from 7.5mg (3 capsules) to 20 mg weekly (8 capsules) by week 8.

Year 1 E+M

Etanercept injection- two injections 25 mg weekly (given at the same time at different sites) + oral Methotrexate capsules weekly (same day as injection).

MTX dose is a forced titration from 7.5mg (3 capsules) to 20 mg weekly (8 capsules) by week 8.


Participant Flow for 2 periods

Period 1:   Year 1
    Year 1 E+M / Year 2 E+M     Year 1 M / Year 2 E+M     Year 1 E+M / Year 2 E     Year 1 M / Year 2 M     Year 1 M+Placebo     Year 1 E+M  
STARTED     0     0     0     0     268     274  
COMPLETED     0     0     0     0     189     221  
NOT COMPLETED     0     0     0     0     79     53  
Adverse Event                 0                 0                 0                 0                 34                 27  
System Toxicity                 0                 0                 0                 0                 0                 1  
Lack of Efficacy                 0                 0                 0                 0                 24                 9  
Compliance                 0                 0                 0                 0                 5                 1  
Lost to Follow-up                 0                 0                 0                 0                 1                 0  
Missed >4 consecutive doses                 0                 0                 0                 0                 3                 2  
Protocol deviation                 0                 0                 0                 0                 2                 3  
Physician Decision                 0                 0                 0                 0                 1                 0  
Withdrawal by Subject                 0                 0                 0                 0                 8                 9  
Protocol Violation                 0                 0                 0                 0                 1                 1  

Period 2:   Year 2
    Year 1 E+M / Year 2 E+M     Year 1 M / Year 2 E+M     Year 1 E+M / Year 2 E     Year 1 M / Year 2 M     Year 1 M+Placebo     Year 1 E+M  
STARTED     111 [1]   90     111 [1]   99     0     0  
COMPLETED     104     74     93     76     0     0  
NOT COMPLETED     7     16     18     23     0     0  
Adverse Event                 3                 7                 5                 9                 0                 0  
Lack of Efficacy                 0                 1                 7                 7                 0                 0  
Compliance                 1                 0                 0                 2                 0                 0  
Lost to Follow-up                 0                 0                 1                 1                 0                 0  
Missed >4 consecutive doses                 1                 1                 1                 0                 0                 0  
Protocol deviation                 0                 1                 0                 0                 0                 0  
Physician Decision                 1                 1                 0                 0                 0                 0  
Withdrawal by Subject                 1                 5                 4                 3                 0                 0  
System toxicity                 0                 0                 0                 1                 0                 0  
[1] A patient with Year 1 termination had taken drug briefly during Year 2 and thus counted in the data.



  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
Year 1 M+Placebo

Oral Methotrexate capsules once weekly + two injections of placebo given at the same time at different sites.

MTX dose is a forced titration from 7.5mg (3 capsules) to 20 mg weekly (8 capsules) by week 8.

Year 1 E+M

Etanercept injection- two injections 25 mg weekly (given at the same time at different sites) + oral Methotrexate capsules weekly (same day as injection).

MTX dose is a forced titration from 7.5mg (3 capsules) to 20 mg weekly (8 capsules) by week 8.

Total Total of all reporting groups

Baseline Measures
    Year 1 M+Placebo     Year 1 E+M     Total  
Number of Participants  
[units: participants]
  268     274     542  
Age [1]
[units: years]
Median ( Full Range )
  51.50  
  ( 20.00 to 84.00 )  
  52.50  
  ( 18.00 to 82.00 )  
  52.00  
  ( 18.00 to 84.00 )  
Gender [2]
[units: Year¬†1¬†participants]
     
Female     194     204     398  
Male     74     70     144  
[1] Year 1 Overall Number of Baseline Participants is 542
[2] Year 1 participants collected from Arms M and E+M equal the stated overall participant population of 542. 411 of those participants were then entered into Year 2 Arms E+M/E+M, M/M+E, E+M/E, M/M. This measure provides the gender population for Year 1 only in order to accurately reflect the overall baseline population of 542.



  Outcome Measures
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1.  Primary:   The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.   [ Time Frame: 12 months ]
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Measure Type Primary
Measure Title The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.
Measure Description Effects of the combination of etanercept and methotrexate to methotrexate alone on clinical disease activity. DAS28 scale 0 - 10, 3.2 or lower showing controlled disease while 5.1 implies active disease.
Time Frame 12 months  
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 analysis population is the modified intent to treat participants from year 1, treatment arms M and E+M.

Reporting Groups
  Description
Year 1 M Oral methotrexate capsules 7.5mg weekly and etanercept placebo at the same day and time.
Year 1 E+M etanercept injection 50mg once weekly and oral methotrexate capsules 7.5 mg once weekly at the same time

Measured Values
    Year 1 M     Year 1 E+M  
Number of Participants Analyzed  
[units: participants]
  263     265  
The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.  
[units: participants]
  73     132  


Statistical Analysis 1 for The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.
Groups [1] All groups
Method [2] Fisher Exact
P Value [3] <0.001
Risk Difference (RD) [4] 22.0
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  E+M (49.8%) - M (27.8%) creates the risk difference estimated value.



2.  Primary:   Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5.   [ Time Frame: 12 months ]

3.  Secondary:   Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death   [ Time Frame: 12 and 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
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  More Information