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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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

Other trials in Philippines

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

Other trials in South Korea

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

Other trials in Malaysia

India4 sites
  • Study site

    Bangalore, 560017

  • Study site

    Bangalore, 560034

  • Study site

    Hyderabaad, 500082

  • Study site

    New Delhi, 110029

Other trials in India

Taiwan3 sites
  • Study site

    Kaohsiung City, 807

  • Study site

    Taipei, 100

  • Study site

    Taipei, 112

Other trials in Taiwan

Hong Kong1 site
  • Study site

    Hong Kong

Other trials in Hong Kong

Singapore1 site
  • Study site

    Singapore, 308433

Other trials in Singapore

Thailand1 site
  • Study site

    Bangkok, 10400

Other trials in Thailand

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.

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 groups in NCT00422227
Study groupRoleWhat they receive
1Active comparatorEtanercept + Methotrexate
Receives: Drug: Etanercept , Methotrexate
2Active comparatorDMARD 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.

  1. 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)
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  1. First posted15 Jan 2007 (estimated)
  2. Study startJun 2007
  3. Primary completionMar 2009
  4. Study completionMar 2009

Resources

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)
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
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 24907147
  • Bae 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

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.

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