Rheumatoid ArthritisPhase 4NCT00195494

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

A Phase 4 study testing Etanercept and Methotrexate in people with Rheumatoid Arthritis, run by Wyeth is now a wholly owned subsidiary of Pfizer at 1 site in United States.

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

To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change and clinical disease activity in subjects with early RA over 12 months. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: Etanercept and Methotrexate
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 542 participants
Where: 1 siteUnited States
Study dates: Nov 2004to Mar 2008
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Satisfies the 1987 ACR Revised Criteria for Rheumatoid Arthritis
Has RA greater than or equal to 3 months and less than or equal to 2 years

Who cannot join

Received any previous treatment with MTX
Received any previous treatment with ETN or other tumour necrosis factor antagonist

Trial locations and contacts

1 site in 1 country.

United States1 site

Study site
Denver, Colorado, 80230

Other trials in United States

About this study

Official title: A 24-Month,Randomized,Double-Blind,Two-Period Study to Evaluate the Efficacy and Safety of the Combination of Etanercept and Methotrexate and Methotrexate Alone in Subjects With Early Rheumatoid Arthritis

To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change and clinical disease activity in subjects with early RA over 12 months.

Conditions: Rheumatoid Arthritis
Being tested: Etanercept, Methotrexate, Placebo
Keywords: Rheumatoid Arthritis
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EtanerceptDrug
Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 \& 2
Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2
Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2
MethotrexateDrug
Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 \& 2
Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2
Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2
Group 2b: Oral Methotrexate weekly for both Periods 1 and 2
PlaceboDrug
Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2
Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2

Study groups in NCT00195494
Study group	Role	What they receive
1a	Active comparator	Etanercept + Methorexate for Period 1 (first 12 months) and Period 2 (Second 12 months) Receives: Drug: Etanercept; Drug: Methotrexate
1b	Active comparator	Etanercept + Methotrexate for Period 1 (First 12 months) and Etanercept alone for Period 2 (Second 12 months) Receives: Drug: Etanercept; Drug: Methotrexate; Drug: Placebo
2a	Active comparator	Methotrexate alone in Period 1 (First 12 months) and etanercept + Methotrexate in Period 2 (Second 12 months) Receives: Drug: Etanercept; Drug: Methotrexate; Drug: Placebo
2b	Active comparator	Methotrexate alone in Period 1 (First 12 months) and Methotrexate alone in Period 2 (Second 12 months) Receives: Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.
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.
Measured: 12 months
Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5.
The (van der Heijde) modified total Sharp score (mTSS) is the sum of scores for erosions (range 0-280) and joint space narrowings (range 0-168) and thus has a total range of (0 - 448 ), where zero is the best score , indicating no damage.
Measured: 12 months

Secondary outcomes (1)

Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death
Safety report for entire trial where participants reported a serious adverse event that led to death.
Measured: 12 and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2004Mar 2008

First posted19 Sep 2005 (estimated)
Study startNov 2004
Primary completionMar 2008
Study completionMar 2008

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 (4)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: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 542 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00195494
Sponsor's protocol ID: 0881A-101548
Status last verified: Aug 2012
First submitted: 13 Sep 2005
Last updated: 5 Sep 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Fleischmann RM, van der Heijde D, Gardiner PV, Szumski A, Marshall L, Bananis E. DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable. RMD Open. 2017 Jan 30;3(1):e000382. doi: 10.1136/rmdopen-2016-000382. eCollection 2017.
PubMed 28255449
Gallo G, Brock F, Kerkmann U, Kola B, Huizinga TW. Efficacy of etanercept in combination with methotrexate in moderate-to-severe rheumatoid arthritis is not dependent on methotrexate dosage. RMD Open. 2016 Apr 21;2(1):e000186. doi: 10.1136/rmdopen-2015-000186. eCollection 2016.
PubMed 27175292
Zhang W, Sun H, Emery P, Sato R, Singh A, Freundlich B, Anis AH. Does achieving clinical response prevent work stoppage or work absence among employed patients with early rheumatoid arthritis? Rheumatology (Oxford). 2012 Feb;51(2):270-4. doi: 10.1093/rheumatology/ker189. Epub 2011 Jun 29.
PubMed 21719418
Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, Singh A, Pedersen RD, Koenig AS, Freundlich B. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008 Aug 2;372(9636):375-82. doi: 10.1016/S0140-6736(08)61000-4. Epub 2008 Jul 16.
PubMed 18635256

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 24-Month,Randomized,Double-Blind,Two-Period Study to Evaluate the Efficacy and Safety of the Combination of Etanercept and Methotrexate and Methotrexate Alone in Subjects With Early Rheumatoid Arthritis
ClinicalTrials.gov ID: NCT00195494
Acronym / sponsor ID: 0881A-101548
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 542 participants (actual)
Lead sponsor: Wyeth is now a wholly owned subsidiary of PfizerIndustry (pharma, biotech, devices)
Study start: Nov 2004
Primary completion: Mar 2008 (actual)
Study completion: Mar 2008 (actual)
First posted: 19 Sep 2005 (estimated)
Results: Posted 5 Sep 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change and clinical disease activity in subjects with early RA over 12 months.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
1a	Active comparator	Drug: Etanercept, Drug: MethotrexateEtanercept + Methorexate for Period 1 (first 12 months) and Period 2 (Second 12 months)
1b	Active comparator	Drug: Etanercept, Drug: Methotrexate, Drug: PlaceboEtanercept + Methotrexate for Period 1 (First 12 months) and Etanercept alone for Period 2 (Second 12 months)
2a	Active comparator	Drug: Etanercept, Drug: Methotrexate, Drug: PlaceboMethotrexate alone in Period 1 (First 12 months) and etanercept + Methotrexate in Period 2 (Second 12 months)
2b	Active comparator	Drug: MethotrexateMethotrexate alone in Period 1 (First 12 months) and Methotrexate alone in Period 2 (Second 12 months)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Satisfies the 1987 ACR Revised Criteria for Rheumatoid Arthritis
Has RA greater than or equal to 3 months and less than or equal to 2 years

Key exclusion criteria (2 listed)

Received any previous treatment with MTX
Received any previous treatment with ETN or other tumour necrosis factor antagonist

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
EtanerceptGroup 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 \& 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2	Drug	1a, 1b, 2a
MethotrexateGroup 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 \& 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2	Drug	1a, 1b, 2a, 2b
PlaceboGroup 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2	Drug	1b, 2a

Primary outcome

The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.
Time frame: 12 months
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.
Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5.
Time frame: 12 months
The (van der Heijde) modified total Sharp score (mTSS) is the sum of scores for erosions (range 0-280) and joint space narrowings (range 0-168) and thus has a total range of (0 - 448 ), where zero is the best score , indicating no damage.

1 secondary outcome

Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death
Time frame: 12 and 24 months

Results and safety

Results posted to the registry on 5 Sep 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Year 1 E+M / Year 2 E+M	0	0
Year 1 M / Year 2 E+M	0	0
Year 1 E+M / Year 2 E	0	0
Year 1 M / Year 2 M	0	0
Year 1 M+Placebo	268	189
Year 1 E+M	274	221

Primary outcome: The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.

Time frame: 12 months. Number. Unit: participants

Measure	Year 1 M n = 263	Year 1 E+M n = 265
Value	73	132

Year 1 M vs Year 1 E+M: Risk Difference (RD): 22.0, p <0.001, Fisher Exact

Population analysed: The analysis population is the modified intent to treat participants from year 1, treatment arms M and E+M.

Primary outcome: Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5.

Time frame: 12 months. Number. Unit: participants

Measure	Year 1 M n = 230	Year 1 E+M n = 246
Value	135	196

Year 1 M vs Year 1 E+M: Risk Difference (RD): 21.0, p <0.001, Fisher Exact

Population analysed: The analysis population is the modified intent to treat participants from year 1, treatment arms M and E+M.

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Year 1 E+M / Year 2 E+M	8 of ?	91 of ?	Not reported
Year 1 M / Year 2 E+M	11 of ?	71 of ?	Not reported
Year 1 E+M / Year 2 E	10 of ?	89 of ?	Not reported
Year 1 M / Year 2 M	12 of ?	79 of ?	Not reported
Year 1 M+Placebo	34 of ?	241 of ?	Not reported
Year 1 E+M	33 of ?	246 of ?	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28255449Fleischmann RM, van der Heijde D, Gardiner PV, Szumski A, Marshall L, Bananis E. DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable. RMD Open. 2017 Jan 30;3(1):e000382. doi: 10.1136/rmdopen-2016-000382. eCollection 2017.
Derived from this study: PubMed 27175292Gallo G, Brock F, Kerkmann U, Kola B, Huizinga TW. Efficacy of etanercept in combination with methotrexate in moderate-to-severe rheumatoid arthritis is not dependent on methotrexate dosage. RMD Open. 2016 Apr 21;2(1):e000186. doi: 10.1136/rmdopen-2015-000186. eCollection 2016.
Derived from this study: PubMed 21719418Zhang W, Sun H, Emery P, Sato R, Singh A, Freundlich B, Anis AH. Does achieving clinical response prevent work stoppage or work absence among employed patients with early rheumatoid arthritis? Rheumatology (Oxford). 2012 Feb;51(2):270-4. doi: 10.1093/rheumatology/ker189. Epub 2011 Jun 29.
Derived from this study: PubMed 18635256Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, Singh A, Pedersen RD, Koenig AS, Freundlich B. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008 Aug 2;372(9636):375-82. doi: 10.1016/S0140-6736(08)61000-4. Epub 2008 Jul 16.

Related trials for Rheumatoid Arthritis

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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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Etanercept and Methotrexate in people with Rheumatoid Arthritis, run by Wyeth is now a wholly owned subsidiary of Pfizer at 1 site in United States.

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 2 inclusion and 2 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 5 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 5 Sep 2012). 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?

The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6. (time frame: 12 months). The study lists 2 primary outcomes in all. 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 NCT00195494, which also lists 4 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 5 Sep 2012.