Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00565409




Registration number
NCT00565409
Ethics application status
Date submitted
28/11/2007
Date registered
30/11/2007
Date last updated
10/08/2015

Titles & IDs
Public title
Study Comparing Etanercept in Combination With Methotrexate in Subjects With Rheumatoid Arthritis
Scientific title
A Randomized, Double-Blind Study Comparing the Safety & Efficacy of Once-Weekly Etanercept 50 mg, Etanercept 25 mg, & Placebo in Combination With Methotrexate in Subjects With Active Rheumatoid Arthritis
Secondary ID [1] 0 0
B1801003
Secondary ID [2] 0 0
0881A1-4423
Universal Trial Number (UTN)
Trial acronym
PRESERVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthritis, Rheumatoid 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Etanercept
Treatment: Drugs - Methotrexate
Treatment: Drugs - Etanercept
Treatment: Drugs - Methotrexate
Treatment: Drugs - Placebo
Treatment: Drugs - Methotrexate

Active comparator: 1 -

Active comparator: 2 -

Placebo comparator: 3 -


Treatment: Drugs: Etanercept
Subcutaneous (SC), 50 mg, once weekly for 88 weeks

Treatment: Drugs: Methotrexate
Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks.

If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).

Treatment: Drugs: Etanercept
Subcutaneous (SC), 25 mg, once weekly from week 36 to week 88.

Treatment: Drugs: Methotrexate
Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks.

If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).

Treatment: Drugs: Placebo
Subcutaneous (SC), once weekly from week 36 to week 88.

Treatment: Drugs: Methotrexate
Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks.

If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving 28 Joint Disease Activity Score (DAS28) Less Than or Equal to (=) 3.2 at Week 88
Timepoint [1] 0 0
Week 88
Secondary outcome [1] 0 0
Percentage of Participants Achieving DAS28 Low Disease Activity or Remission at Baseline, Weeks 4, 8, 12, 20, 28 and 36
Timepoint [1] 0 0
Baseline, Weeks 4, 8, 12, 20, 28, 36
Secondary outcome [2] 0 0
Percentage of Participants Achieving DAS28 Low Disease Activity or Remission
Timepoint [2] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [3] 0 0
Change From Baseline in DAS28 at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [3] 0 0
Baseline, Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [4] 0 0
Change From Week 36 in DAS28 at Weeks 40, 48, 56, 64, 72, 80 and 88
Timepoint [4] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [5] 0 0
Time to Loss of Low Disease Activity DAS28 and a Change of = 0.6 Units in the DAS28
Timepoint [5] 0 0
Week 36 up to Week 88
Secondary outcome [6] 0 0
Time to Loss of Low Disease Activity DAS28
Timepoint [6] 0 0
Week 36 up to Week 88
Secondary outcome [7] 0 0
Proportion of Time Participants Had Low Disease Activity DAS28 Week 36 to Week 88
Timepoint [7] 0 0
Week 36 up to Week 88
Secondary outcome [8] 0 0
Change From Baseline in Prorated Swollen Joint Count at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [8] 0 0
Baseline, Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [9] 0 0
Prorated Swollen Joint Count at Week 36
Timepoint [9] 0 0
Week 36
Secondary outcome [10] 0 0
Change From Week 36 in Prorated Swollen Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
Timepoint [10] 0 0
Week 36, Weeks 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [11] 0 0
Change From Baseline in the Painful Joint Count at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [11] 0 0
Baseline, Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [12] 0 0
Painful Joint Count at Week 36
Timepoint [12] 0 0
Week 36
Secondary outcome [13] 0 0
Change From Week 36 in Painful Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
Timepoint [13] 0 0
Weeks 36 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [14] 0 0
Change From Baseline in the Physician Global Assessment (PGA) at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [14] 0 0
Baseline, Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [15] 0 0
PGA Score at Week 36
Timepoint [15] 0 0
Week 36
Secondary outcome [16] 0 0
Change From Week 36 in the PGA Score at Weeks 40, 48, 56, 64, 72, 80 and 88
Timepoint [16] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [17] 0 0
Change From Baseline in Patient's Global Assessment (PtGA) of Arthritis Pain at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [17] 0 0
Baseline, Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [18] 0 0
PtGA of Arthritis Pain at Week 36
Timepoint [18] 0 0
Week 36
Secondary outcome [19] 0 0
Change From Week 36 in PtGA of Arthritis Pain at Weeks 40, 48, 56, 64, 72, 80, 88
Timepoint [19] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80, 88
Secondary outcome [20] 0 0
Change From Baseline in Duration of Morning Stiffness at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [20] 0 0
Baseline, Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [21] 0 0
Duration of Morning Stiffness at Week 36
Timepoint [21] 0 0
Week 36
Secondary outcome [22] 0 0
Change From Week 36 in Duration of Morning Stiffness at Weeks 40, 48, 56, 64, 72, 80, 88
Timepoint [22] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80, 88
Secondary outcome [23] 0 0
Change From Baseline in General Health at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [23] 0 0
Baseline, Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [24] 0 0
General Health at Week 36
Timepoint [24] 0 0
Week 36
Secondary outcome [25] 0 0
Change From Week 36 in General Health at Weeks 40, 48, 56, 64, 72, 80, 88
Timepoint [25] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80, 88
Secondary outcome [26] 0 0
Change From Baseline in Pain at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [26] 0 0
Baseline, Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [27] 0 0
Pain at Week 36
Timepoint [27] 0 0
Week 36
Secondary outcome [28] 0 0
Change From Week 36 in Pain at Weeks 40, 48, 56, 64, 72, 80 and 88
Timepoint [28] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [29] 0 0
Percentage of Participants Achieving an Acceptable State on the Patient Acceptable Symptom State (PASS) at Baseline and Week 36
Timepoint [29] 0 0
Baseline, Week 36
Secondary outcome [30] 0 0
Percentage of Participants Achieving an Acceptable State on the PASS at Week 36 and Weeks 64 and 88
Timepoint [30] 0 0
Weeks 36, 64 and 88
Secondary outcome [31] 0 0
Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good or Moderate Response at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [31] 0 0
Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [32] 0 0
Percentage of Participants Achieving EULAR Good or Moderate Response at Week 36, 40, 48, 56, 64, 72, 80 and 88
Timepoint [32] 0 0
Week 36, 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [33] 0 0
Percentage of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [33] 0 0
Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [34] 0 0
Percentage of Participants With an ACR20 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Timepoint [34] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [35] 0 0
Percentage of Participants With an ACR50 Response at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [35] 0 0
Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [36] 0 0
Percentage of Participants With an ACR50 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Timepoint [36] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [37] 0 0
Percentage of Participants With an ACR70 Response at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [37] 0 0
Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [38] 0 0
Percentage of Participants With an ACR70 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Timepoint [38] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [39] 0 0
Percentage of Participants With an ACR90 Response at Weeks 4, 8, 12, 20, 28 and 36
Timepoint [39] 0 0
Weeks 4, 8, 12, 20, 28 and 36
Secondary outcome [40] 0 0
Percentage of Participants With an ACR90 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Timepoint [40] 0 0
Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Secondary outcome [41] 0 0
DAS28 at Week 36
Timepoint [41] 0 0
Week 36

Eligibility
Key inclusion criteria
* Diagnosis of rheumatoid arthritis.
* Currently receiving an optimal dose of oral Methotrexate (MTX)(at least 15 mg/week but no more than 25 mg/week) for the treatment of rheumatoid arthritis.
* Active rheumatoid arthritis at the time of screening.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous or current treatment with etanercept, other tumor necrosis factor-alpha (TNF) inhibitors, or other biologic agents.
* Concurrent treatment with any disease-modifying anti-rheumatoid drugs (DMARD), other than MTX within 28 days before baseline.
* Concurrent treatment with more than 1 non-steroid anti-inflammatory drug (NSAID) at baseline.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2011
Sample size
Target
Accrual to date
Final
834
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Campsie
Recruitment hospital [2] 0 0
Pfizer Investigational Site - Kogarah
Recruitment hospital [3] 0 0
Pfizer Investigational Site - Maroochydore
Recruitment hospital [4] 0 0
Pfizer Investigational Site - Daw Park
Recruitment hospital [5] 0 0
Pfizer Investigational Site - Heidelberg West
Recruitment hospital [6] 0 0
Pfizer Investigational Site - Malvern
Recruitment hospital [7] 0 0
Pfizer Investigational Site - Victoria Park
Recruitment postcode(s) [1] 0 0
2194 - Campsie
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
4558 - Maroochydore
Recruitment postcode(s) [4] 0 0
5041 - Daw Park
Recruitment postcode(s) [5] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [6] 0 0
3145 - Malvern
Recruitment postcode(s) [7] 0 0
6100 - Victoria Park
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Wien
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Liege
Country [4] 0 0
Belgium
State/province [4] 0 0
Yvoir
Country [5] 0 0
Chile
State/province [5] 0 0
Region Metropolitana
Country [6] 0 0
Colombia
State/province [6] 0 0
Atlantico
Country [7] 0 0
Colombia
State/province [7] 0 0
Cundinamarca
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Brno
Country [9] 0 0
Czech Republic
State/province [9] 0 0
Bruntal
Country [10] 0 0
Czech Republic
State/province [10] 0 0
Praha 2
Country [11] 0 0
Czech Republic
State/province [11] 0 0
Praha 5
Country [12] 0 0
Czech Republic
State/province [12] 0 0
Zlin
Country [13] 0 0
Former Serbia and Montenegro
State/province [13] 0 0
Belgrade
Country [14] 0 0
Former Serbia and Montenegro
State/province [14] 0 0
Niska Banja
Country [15] 0 0
France
State/province [15] 0 0
Corbeil-Essonnes
Country [16] 0 0
France
State/province [16] 0 0
Le Kremlin Bicetre
Country [17] 0 0
France
State/province [17] 0 0
Le Mans
Country [18] 0 0
France
State/province [18] 0 0
Montpellier
Country [19] 0 0
France
State/province [19] 0 0
Nice
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
France
State/province [21] 0 0
Strasbourg
Country [22] 0 0
France
State/province [22] 0 0
Toulouse
Country [23] 0 0
Germany
State/province [23] 0 0
Berlin
Country [24] 0 0
Germany
State/province [24] 0 0
Hamburg-Eilbek
Country [25] 0 0
Germany
State/province [25] 0 0
Koeln
Country [26] 0 0
Germany
State/province [26] 0 0
Leipzig
Country [27] 0 0
Germany
State/province [27] 0 0
Wuerzburg
Country [28] 0 0
Hungary
State/province [28] 0 0
Budapest
Country [29] 0 0
Hungary
State/province [29] 0 0
Debrecen
Country [30] 0 0
Hungary
State/province [30] 0 0
Szombathely
Country [31] 0 0
Italy
State/province [31] 0 0
CT
Country [32] 0 0
Italy
State/province [32] 0 0
TO
Country [33] 0 0
Italy
State/province [33] 0 0
Roma
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Daejeon
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Incheon
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Korea
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Anyang-si Gyeonggi-do
Country [39] 0 0
Mexico
State/province [39] 0 0
Yucatan
Country [40] 0 0
Mexico
State/province [40] 0 0
Guadalajara
Country [41] 0 0
Mexico
State/province [41] 0 0
Mexico City
Country [42] 0 0
Mexico
State/province [42] 0 0
Mexico DF
Country [43] 0 0
Mexico
State/province [43] 0 0
Monterrey
Country [44] 0 0
Mexico
State/province [44] 0 0
Queretaro
Country [45] 0 0
Netherlands
State/province [45] 0 0
Heerlen
Country [46] 0 0
Poland
State/province [46] 0 0
Bydgoszcz
Country [47] 0 0
Poland
State/province [47] 0 0
Lodz
Country [48] 0 0
Poland
State/province [48] 0 0
Lublin
Country [49] 0 0
Poland
State/province [49] 0 0
Szczecin
Country [50] 0 0
Poland
State/province [50] 0 0
Warszawa
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Moscow
Country [52] 0 0
Russian Federation
State/province [52] 0 0
St Petersburg
Country [53] 0 0
Russian Federation
State/province [53] 0 0
St. Petersburg
Country [54] 0 0
Spain
State/province [54] 0 0
A Coruña
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
State/province [56] 0 0
La Coruña
Country [57] 0 0
Spain
State/province [57] 0 0
Malaga
Country [58] 0 0
Spain
State/province [58] 0 0
Sevilla
Country [59] 0 0
Sweden
State/province [59] 0 0
Falun
Country [60] 0 0
Sweden
State/province [60] 0 0
Oskarström
Country [61] 0 0
Taiwan
State/province [61] 0 0
ROC
Country [62] 0 0
Taiwan
State/province [62] 0 0
Kaohsiung City
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Lancashire
Country [64] 0 0
United Kingdom
State/province [64] 0 0
West Midlands

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To compare the efficacy of the combination of etanercept 50 mg once weekly plus methotrexate with that of methotrexate monotherapy in the treatment of rheumatoid arthritis over 88 weeks.
Trial website
https://clinicaltrials.gov/study/NCT00565409
Trial related presentations / publications
Tanaka Y, Smolen JS, Jones H, Szumski A, Marshall L, Emery P. The effect of deep or sustained remission on maintenance of remission after dose reduction or withdrawal of etanercept in patients with rheumatoid arthritis. Arthritis Res Ther. 2019 Jul 5;21(1):164. doi: 10.1186/s13075-019-1937-4.
Smolen JS, Pedersen R, Jones H, Mahgoub E, Marshall L. Impact of flare on radiographic progression after etanercept continuation, tapering or withdrawal in patients with rheumatoid arthritis. Rheumatology (Oxford). 2020 Jan 1;59(1):153-164. doi: 10.1093/rheumatology/kez224.
Smolen JS, Szumski A, Koenig AS, Jones TV, Marshall L. Predictors of remission with etanercept-methotrexate induction therapy and loss of remission with etanercept maintenance, reduction, or withdrawal in moderately active rheumatoid arthritis: results of the PRESERVE trial. Arthritis Res Ther. 2018 Jan 16;20(1):8. doi: 10.1186/s13075-017-1484-9.
Smolen JS, Strand V, Koenig AS, Szumski A, Kotak S, Jones TV. Discordance between patient and physician assessments of global disease activity in rheumatoid arthritis and association with work productivity. Arthritis Res Ther. 2016 May 21;18(1):114. doi: 10.1186/s13075-016-1004-3.
Smolen JS, Nash P, Durez P, Hall S, Ilivanova E, Irazoque-Palazuelos F, Miranda P, Park MC, Pavelka K, Pedersen R, Szumski A, Hammond C, Koenig AS, Vlahos B. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet. 2013 Mar 16;381(9870):918-29. doi: 10.1016/S0140-6736(12)61811-X. Epub 2013 Jan 17.
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00565409