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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00195494
First Posted: September 19, 2005
Last Update Posted: September 5, 2012
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.
Information provided by (Responsible Party):
Wyeth is now a wholly owned subsidiary of Pfizer
Results First Submitted: March 31, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: Etanercept
Drug: Methotrexate
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
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 
Overall Participants Analyzed 
[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) 
[1] Year 1 Overall Number of Baseline Participants is 542
Gender [1] 
[Units: Year 1 participants]
     
Female   194   204   398 
Male   74   70   144 
[1] 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
  Show All Outcome Measures

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 ]

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
  Hide Other Adverse Events

Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.


Other Adverse Events
    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
Total, Other (not including serious) Adverse Events             
# participants affected   91   71   89   79   241   246 
Blood and lymphatic system disorders             
Blood and lymphatic             
# participants affected / at risk   6/111 (5.41%)   2/90 (2.22%)   2/111 (1.80%)   4/99 (4.04%)   4/268 (1.49%)   20/274 (7.30%) 
Cardiac disorders             
Cardiac disorders             
# participants affected / at risk   0/111 (0.00%)   5/90 (5.56%)   3/111 (2.70%)   1/99 (1.01%)   14/268 (5.22%)   14/274 (5.11%) 
Ear and labyrinth disorders             
Ear and labyrinth             
# participants affected / at risk   0/111 (0.00%)   0/90 (0.00%)   0/111 (0.00%)   0/99 (0.00%)   16/268 (5.97%)   11/274 (4.01%) 
Eye disorders             
Eye             
# participants affected / at risk   5/111 (4.50%)   4/90 (4.44%)   5/111 (4.50%)   7/99 (7.07%)   20/268 (7.46%)   28/274 (10.22%) 
Gastrointestinal disorders             
Abdominal pain upper             
# participants affected / at risk   0/111 (0.00%)   0/90 (0.00%)   0/111 (0.00%)   0/99 (0.00%)   27/268 (10.07%)   23/274 (8.39%) 
Diarhhea             
# participants affected / at risk   4/111 (3.60%)   2/90 (2.22%)   6/111 (5.41%)   7/99 (7.07%)   20/268 (7.46%)   24/274 (8.76%) 
Nausea             
# participants affected / at risk   8/111 (7.21%)   8/90 (8.89%)   4/111 (3.60%)   8/99 (8.08%)   48/268 (17.91%)   53/274 (19.34%) 
Vomiting             
# participants affected / at risk   0/111 (0.00%)   0/90 (0.00%)   0/111 (0.00%)   0/99 (0.00%)   18/268 (6.72%)   11/274 (4.01%) 
Dyspepsia             
# participants affected / at risk   1/111 (0.90%)   0/90 (0.00%)   3/111 (2.70%)   5/99 (5.05%)   0/268 (0.00%)   0/274 (0.00%) 
General disorders             
Administration site conditions             
# participants affected / at risk   0/111 (0.00%)   0/90 (0.00%)   0/111 (0.00%)   0/99 (0.00%)   50/268 (18.66%)   67/274 (24.45%) 
Infections and Infestations             
# participants affected / at risk   47/111 (42.34%)   33/90 (36.67%)   49/111 (44.14%)   42/99 (42.42%)   0/268 (0.00%)   0/274 (0.00%) 
Gastroenteritis             
# participants affected / at risk   7/111 (6.31%)   1/90 (1.11%)   1/111 (0.90%)   1/99 (1.01%)   0/268 (0.00%)   0/274 (0.00%) 
Lower respiratory tract infection             
# participants affected / at risk   2/111 (1.80%)   1/90 (1.11%)   4/111 (3.60%)   5/99 (5.05%)   0/268 (0.00%)   0/274 (0.00%) 
Rhinitis             
# participants affected / at risk   2/111 (1.80%)   2/90 (2.22%)   6/111 (5.41%)   1/99 (1.01%)   0/268 (0.00%)   0/274 (0.00%) 
Infections and infestations             
Nasopharyngitis             
# participants affected / at risk   10/111 (9.01%)   10/90 (11.11%)   10/111 (9.01%)   13/99 (13.13%)   42/268 (15.67%)   44/274 (16.06%) 
Upper respiratory tract infections             
# participants affected / at risk   6/111 (5.41%)   8/90 (8.89%)   5/111 (4.50%)   9/99 (9.09%)   19/268 (7.09%)   18/274 (6.57%) 
Urinary tract infections             
# participants affected / at risk   0/111 (0.00%)   2/90 (2.22%)   6/111 (5.41%)   4/99 (4.04%)   10/268 (3.73%)   17/274 (6.20%) 
Injury, poisoning and procedural complications             
Post procedural nausea             
# participants affected / at risk   0/111 (0.00%)   0/90 (0.00%)   0/111 (0.00%)   0/99 (0.00%)   23/268 (8.58%)   18/274 (6.57%) 
Injury, poisoning and procedural complications             
# participants affected / at risk   13/111 (11.71%)   11/90 (12.22%)   15/111 (13.51%)   9/99 (9.09%)   0/268 (0.00%)   0/274 (0.00%) 
Investigations             
Investigations             
# participants affected / at risk   0/111 (0.00%)   0/90 (0.00%)   0/111 (0.00%)   0/99 (0.00%)   50/268 (18.66%)   49/274 (17.88%) 
Alanine aminotransferase increased             
# participants affected / at risk   5/111 (4.50%)   7/90 (7.78%)   2/111 (1.80%)   1/99 (1.01%)   0/268 (0.00%)   0/274 (0.00%) 
Musculoskeletal and connective tissue disorders             
Rheumatoid arthritis             
# participants affected / at risk   6/111 (5.41%)   6/90 (6.67%)   4/111 (3.60%)   15/99 (15.15%)   36/268 (13.43%)   13/274 (4.74%) 
Back pain             
# participants affected / at risk   2/111 (1.80%)   3/90 (3.33%)   4/111 (3.60%)   6/99 (6.06%)   0/268 (0.00%)   0/274 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Neoplasms benign             
# participants affected / at risk   0/111 (0.00%)   7/90 (7.78%)   2/111 (1.80%)   3/99 (3.03%)   0/268 (0.00%)   0/274 (0.00%) 
Nervous system disorders             
Headache             
# participants affected / at risk   8/111 (7.21%)   4/90 (4.44%)   6/111 (5.41%)   4/99 (4.04%)   20/268 (7.46%)   29/274 (10.58%) 
Psychiatric disorders             
Psychiatric             
# participants affected / at risk   0/111 (0.00%)   0/90 (0.00%)   0/111 (0.00%)   0/99 (0.00%)   23/268 (8.58%)   28/274 (10.22%) 
Depression             
# participants affected / at risk   1/111 (0.90%)   5/90 (5.56%)   0/111 (0.00%)   0/99 (0.00%)   0/268 (0.00%)   0/274 (0.00%) 
Renal and urinary disorders             
Renal and urinary             
# participants affected / at risk   8/111 (7.21%)   5/90 (5.56%)   2/111 (1.80%)   5/99 (5.05%)   19/268 (7.09%)   21/274 (7.66%) 
Respiratory, thoracic and mediastinal disorders             
Cough             
# participants affected / at risk   7/111 (6.31%)   2/90 (2.22%)   8/111 (7.21%)   6/99 (6.06%)   26/268 (9.70%)   23/274 (8.39%) 
Skin and subcutaneous tissue disorders             
Alopecia             
# participants affected / at risk   0/111 (0.00%)   0/90 (0.00%)   0/111 (0.00%)   0/99 (0.00%)   8/268 (2.99%)   15/274 (5.47%) 
Rash             
# participants affected / at risk   4/111 (3.60%)   5/90 (5.56%)   3/111 (2.70%)   4/99 (4.04%)   14/268 (5.22%)   16/274 (5.84%) 
Vascular disorders             
Hypertension             
# participants affected / at risk   5/111 (4.50%)   0/90 (0.00%)   3/111 (2.70%)   6/99 (6.06%)   22/268 (8.21%)   17/274 (6.20%) 
* Events were collected by non-systematic assessment



  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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