Rheumatoid ArthritisPhase 4NCT00422227
Study Comparing Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis in the Asia Pacific Region
A Phase 4 study testing Etanercept , Methotrexate and Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide in people with Rheumatoid Arthritis, run by Wyeth is now a wholly owned subsidiary of Pfizer at 27 sites in 8 countries.
Trial summary
The purpose of this study is to compare the efficacy of etanercept with usual disease-modifying anti-rheumatic drug (DMARD) therapy in the treatment of moderate to severe rheumatoid arthritis (RA) over 16 weeks in the Asia Pacific region. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Etanercept , Methotrexate and Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 27 sitesin 8 countries
- Study dates
- Jun 2007to Mar 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of RA
- Currently receiving an adequate dose of methotrexate (MTX) for treatment of RA
- Active RA at time of screening and baseline
Who cannot join
- Previous or current treatment with etanercept (ETN), other tumor necrosis factor-alpha inhibitors, or other biologic agents
- Concurrent treatment with a DMARD, other than MTX, at screening
- Receipt of any DMARD, other than MTX, within 3 months before screening
Trial locations and contacts
27 sites in 8 countries.
27 sites in 8 countries
Philippines6 sites
Study site
Cebu, 6000
Study site
Makati City, 1200
Study site
Manila, 1000
Study site
Manila, 1004
Study site
Manila, 1500
Study site
Quezon City, 1102
South Korea6 sites
Study site
Incheon, Korea, 400-711
Study site
Seoul, Korea, 110-744
Study site
Seoul, Korea, 120-752
Study site
Seoul, Korea, 133-792
Study site
Seoul, Korea, 137-701
Study site
Seoul, Korea, 138-736
Malaysia5 sites
Study site
Ipoh, Perak, 30450
Study site
Kuala Lumpur, 68100
Study site
Pulau Pinang, 10450
Study site
Putrajaya, 62250
Study site
Seremban, 70300
India4 sites
Study site
Bangalore, 560017
Study site
Bangalore, 560034
Study site
Hyderabaad, 500082
Study site
New Delhi, 110029
Taiwan3 sites
Study site
Kaohsiung City, 807
Study site
Taipei, 100
Study site
Taipei, 112
About this study
Official title: A Randomized, Open-Label Study in the Asia-Pacific Region Comparing the Safety and Efficacy of Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis
The purpose of this study is to compare the efficacy of etanercept with usual disease-modifying anti-rheumatic drug (DMARD) therapy in the treatment of moderate to severe rheumatoid arthritis (RA) over 16 weeks in the Asia Pacific region.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Etanercept , Methotrexate, Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Etanercept , MethotrexateDrug
- Etanercept: 25 mg twice weekly over 16 weeks, SC
- Methotrexate: > 7.5 mg/week and no more than 25 mg/week, PO
Methotrexate; sulfasalazine; hydroxychloroquine;leflunomideDrug
- Methotrexate: at least 7.5 mg/wk and not more than 25 mg/wk.;PO
- Sulfasalazine: Start treatment w/500 mg daily for 1 wk, thereafter increase dose by 1 tab each wk to a max of 3 g/day;PO
- Hydroxychloroquine:400 mg daily in divided dose, may be reduced to 200 mg. Max: 6.5 mg/kg/day
- Leflunomide: Initially, loading dose 100 mg daily for 3 days. Maintenance: 20 mg daily
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Etanercept + Methotrexate Receives: Drug: Etanercept , Methotrexate |
| 2 | Active comparator | DMARD therapy Methotrexate + Sulfasalazine/Hydroxychloroquine/Leflunomide Receives: Drug: Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Adjusted Mean of American College of Rheumatology Response (ACR-N) Area Under Curve (AUC) Over 16 Weeks
ACR-N = the lowest of 3 values (percent change in the number of swollen joints, percent change in the number of tender joints, and median of the other 5 measures in the ACR core data set). Negative numbers indicate worsening.
The ACR-N AUC was calculated using the trapezoidal rule as the ACR-N multiplied by the duration of the assessment period (in weeks) and was presented as %-weeks.
Measured: 16 weeks
Secondary outcomes (9)
Percentage of Participants Achieving ACR 20, 50, and 70 Responses
Response includes improvement in tender or swollen joints as well as 20 percent improvement in three of the other five criteria. Required: ≥ 20%, 50% or 70% improvement in tender joint count ≥ 20% , 50% or 70% improvement in swollen joint count and at least 20%, 50%, 70% improvement in 3 of the following 5:Patient pain assessment , Patient global assessment ,Physician global assessment, Patient self-assessed disability.
Measured: Week 16
Percentage of Participants Achieving DAS28 <3.2 (Low Disease Activity) and <2.6 (Remission)
Disease Activity Score 28 based on 28 Joints (DAS28) is the calculation of DAS28: DAS28 = 0.56 sqrt (28 painful joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln erythrocyte sedimentation rate (ESR)) + 0.014 (General Health) (GH). GH = Subject general health visual analog scale (0-10 mm).
Measured: Week 16
Percent Change From Baseline in DAS28 at Week 16
Disease Activity Score 28 based on 28 Joints (DAS28) is the calculation of DAS28: DAS28 = 0.56 sqrt (28 painful joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln erythrocyte sedimentation rate (ESR)) + 0.014 (General Health) (GH). GH = Subject general health visual analog scale (0-10 mm).
Measured: Week 16
Percentage of Participants Achieving European League Against Rheumatism (EULAR) Moderate or Good Response
EULAR Response Criteria DAS28) improvement at week 16. Good response was defined as >1.2 improvement in DAS from Baseline and DAS attained during follow-up of ≤2.4. Non-responders were participants with improvement of ≤0.6 or participants with improvement of >0.6 but ≤1.2 and DAS attained during follow-up of >3.7. Remaining participants were classified as moderate. Scores of good and moderate were considered to have therapeutic response.
Measured: Week 16
Percentage of Participants With DAS28 Improvement of ≥0.6 and ≥1.2
Disease Activity Score 28 based on 28 Joints (DAS28) is the calculation of DAS28: DAS28 = 0.56 sqrt (28 painful joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln erythrocyte sedimentation rate (ESR) + 0.014 (General Health) (GH). GH = Subject general health visual analog scale (0-10 mm).
Measured: Week 16
Percent Change From Baseline in Painful and Swollen Joint Counts
Participant's assessment of pain - A horizontal pain visual analog scale (VAS) (0-100 mm) is used to assess the participants current level of pain; 0 = no pain and 100 = worst pain. Swollen joint count - ACR swollen joint count, an assessment of 28 joints. Joints are classified as either swollen or not swollen.
Measured: Week 2, 4, 8, 12, 16
Percent Change From Baseline in Physician And Subject Global Assessments
The Physician Global Assessment of Disease Activity: The participant's disease activity is estimated over the last two - three days by the physician; A zero (0) means no disease activity and a ten (10) means extreme disease activity. The Subject Global Assessment of Disease Activity: The participant assesses overall arthritis activity. A zero (0) means no disease activity and a ten (10) means extreme disease activity.
Measured: Week 2, 4, 8, 12, 16
Percent Change From Baseline in Duration (Minutes) of Morning Stiffness
The duration of morning stiffness on the day of examination should be determined by asking the following two questions: When did you awaken this morning? When were you able to resume your normal activities without stiffness? Duration of morning stiffness is equal to the time elapsed between the above two times in minutes; If none is present enter 0, If morning stiffness is still continuing, please indicate average of duration of stiffness over the past 3 days. If stiffness persists the entire day 1440 minutes (24h x 60 minutes) should be recorded.
Measured: Week 2, 4, 8, 12, 16
Percent Change From Baseline in General Health, Pain, and Fatigue, Visual Analog Scales
VAS, participant indicates by marking a vertical line at an appropriate position through a horizontal line. The length of the line measures from left (in mm) and the value (in mm) is recorded. General Health VAS, "in general how would you rate your heath over the last 2-3 weeks", 0mm equals very well and 100mm equals extremely bad. Pain VAS: "indicate the amount of pain experienced during the last 2-3 days", 0 mm equals no pain and 100 mm equals pain as bad as it can be. Fatigue VAS: "how fatigued or tired have you been over the last week", range =No Fatigue - Extremely Fatigued.
Measured: Week 2, 4, 8, 12, 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2007 (estimated)
- Study startJun 2007
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wyeth is now a wholly owned subsidiary of Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Medical Monitor, Study director, Wyeth is now a wholly owned subsidiary of PfizerTrial Manager, Principal investigator, For Hong Kong: medinfo@wyeth.comTrial Manager, Principal investigator, For Taiwan: medinfo@wyeth.com
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00422227
- Sponsor's protocol ID
- 0881A1-408
- Status last verified
- Jul 2010
- First submitted
- 11 Jan 2007
- Last updated
- 30 Aug 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Fleischmann R, Koenig AS, Szumski A, Nab HW, Marshall L, Bananis E. Short-term efficacy of etanercept plus methotrexate vs combinations of disease-modifying anti-rheumatic drugs with methotrexate in established rheumatoid arthritis. Rheumatology (Oxford). 2014 Nov;53(11):1984-93. doi: 10.1093/rheumatology/keu235. Epub 2014 Jun 6.
PubMed 24907147Bae SC, Gun SC, Mok CC, Khandker R, Nab HW, Koenig AS, Vlahos B, Pedersen R, Singh A. Improved health outcomes with etanercept versus usual DMARD therapy in an Asian population with established rheumatoid arthritis. BMC Musculoskelet Disord. 2013 Jan 8;14:13. doi: 10.1186/1471-2474-14-13.
PubMed 23294908
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label Study in the Asia-Pacific Region Comparing the Safety and Efficacy of Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT00422227
- Acronym / sponsor ID
- 0881A1-408
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Wyeth is now a wholly owned subsidiary of PfizerIndustry (pharma, biotech, devices)
- Study start
- Jun 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 15 Jan 2007 (estimated)
- Results
- Posted 30 Aug 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the efficacy of etanercept with usual disease-modifying anti-rheumatic drug (DMARD) therapy in the treatment of moderate to severe rheumatoid arthritis (RA) over 16 weeks in the Asia Pacific region.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Etanercept , MethotrexateEtanercept + Methotrexate |
| 2 | Active comparator | Drug: Methotrexate; sulfasalazine; hydroxychloroquine;leflunomideDMARD therapy Methotrexate + Sulfasalazine/Hydroxychloroquine/Leflunomide |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of RA
- Currently receiving an adequate dose of methotrexate (MTX) for treatment of RA
- Active RA at time of screening and baseline
Key exclusion criteria (3 listed)
- Previous or current treatment with etanercept (ETN), other tumor necrosis factor-alpha inhibitors, or other biologic agents
- Concurrent treatment with a DMARD, other than MTX, at screening
- Receipt of any DMARD, other than MTX, within 3 months before screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Etanercept , Methotrexate* Etanercept: 25 mg twice weekly over 16 weeks, SC * Methotrexate: > 7.5 mg/week and no more than 25 mg/week, PO | Drug | 1 |
| Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide* Methotrexate: at least 7.5 mg/wk and not more than 25 mg/wk.;PO * Sulfasalazine: Start treatment w/500 mg daily for 1 wk, thereafter increase dose by 1 tab each wk to a max of 3 g/day;PO * Hydroxychloroquine:400 mg daily in divided dose, may be reduced to 200 mg. Max: 6.5 mg/kg/day * Leflunomide: Initially, loading dose 100 mg daily for 3 days. Maintenance: 20 mg daily | Drug | 2 |
Primary outcome
Change From Baseline in Adjusted Mean of American College of Rheumatology Response (ACR-N) Area Under Curve (AUC) Over 16 Weeks
Time frame: 16 weeks
ACR-N = the lowest of 3 values (percent change in the number of swollen joints, percent change in the number of tender joints, and median of the other 5 measures in the ACR core data set). Negative numbers indicate worsening. The ACR-N AUC was calculated using the trapezoidal rule as the ACR-N multiplied by the duration of the assessment period (in weeks) and was presented as %-weeks.
9 secondary outcomes
Percentage of Participants Achieving ACR 20, 50, and 70 Responses
Time frame: Week 16
Percentage of Participants Achieving DAS28 <3.2 (Low Disease Activity) and <2.6 (Remission)
Time frame: Week 16
Percent Change From Baseline in DAS28 at Week 16
Time frame: Week 16
Percentage of Participants Achieving European League Against Rheumatism (EULAR) Moderate or Good Response
Time frame: Week 16
Percentage of Participants With DAS28 Improvement of ≥0.6 and ≥1.2
Time frame: Week 16
Percent Change From Baseline in Painful and Swollen Joint Counts
Time frame: Week 2, 4, 8, 12, 16
Percent Change From Baseline in Physician And Subject Global Assessments
Time frame: Week 2, 4, 8, 12, 16
Percent Change From Baseline in Duration (Minutes) of Morning Stiffness
Time frame: Week 2, 4, 8, 12, 16
Percent Change From Baseline in General Health, Pain, and Fatigue, Visual Analog Scales
Time frame: Week 2, 4, 8, 12, 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24907147Fleischmann R, Koenig AS, Szumski A, Nab HW, Marshall L, Bananis E. Short-term efficacy of etanercept plus methotrexate vs combinations of disease-modifying anti-rheumatic drugs with methotrexate in established rheumatoid arthritis. Rheumatology (Oxford). 2014 Nov;53(11):1984-93. doi: 10.1093/rheumatology/keu235. Epub 2014 Jun 6.
- Derived from this study: PubMed 23294908Bae SC, Gun SC, Mok CC, Khandker R, Nab HW, Koenig AS, Vlahos B, Pedersen R, Singh A. Improved health outcomes with etanercept versus usual DMARD therapy in an Asian population with established rheumatoid arthritis. BMC Musculoskelet Disord. 2013 Jan 8;14:13. doi: 10.1186/1471-2474-14-13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Wyeth is now a wholly owned subsidiary of Pfizer
Trial Manager principal investigator
For Hong Kong: medinfo@wyeth.com
Trial Manager principal investigator
For Taiwan: medinfo@wyeth.com
27 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Etanercept , Methotrexate and Methotrexate; sulfasalazine; hydroxychloroquine;leflunomide in people with Rheumatoid Arthritis, run by Wyeth is now a wholly owned subsidiary of Pfizer at 27 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in Philippines, South Korea, Malaysia, India, Taiwan and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Adjusted Mean of American College of Rheumatology Response (ACR-N) Area Under Curve (AUC) Over 16 Weeks (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00422227, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2010.