Rheumatoid ArthritisPhase 4RIVERANCT00523692
Remission Induction in Very Early Rheumatoid Arthritis
A Phase 4 study testing Etanercept, methotrexate and depomedrone and depemedrone in people with Rheumatoid Arthritis, run by University Hospital Birmingham at 2 sites in United Kingdom.
Trial summary
Rheumatoid arthritis (RA) is a debilitating chronic immune mediated inflammatory disease which affects 1% of the European population. RA is associated with significant joint damage, disability and an enhanced mortality. 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, methotrexate and depomedrone and depemedrone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Sep 2007to not given
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Age over 18 years
- Synovial swelling of at least 1 joint confirmed by clinical assessment
- Duration of symptoms attributable to inflammatory joint disease (pain, swelling or early morning stiffness of >1 hour) of < 12 weeks.
- Seropositivity for RF and anti-CCP Ab
- Women of childbearing potential or men capable of fathering children must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization) during the study.
- Female subjects of childbearing potential must test negative for pregnancy
Who cannot join
- Previous history of inflammatory arthritis.
- Previous use of DMARDs or anti-TNF-agents.
- Any current inflammatory condition with signs or symptoms that might confound the diagnosis (e.g. connective tissue disorders).
- Clinical evidence of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to study entry.
- Administration, or expected administration, of any live virus or bacterial vaccination within 3 months before the first administration of study agent, or during the trial.
- A history of an infected joint prosthesis, or administration of antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced.
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- Known infection with HIV, hepatitis B, or hepatitis C.
- A serious infection that in the opinion of the investigator precludes receipt of a TNF blocking agent.
- Serious and uncontrolled co-existing disease that in the opinion of the investigator preclude the use of TNF-blocking medication, methotrexate or depomedrone (including pulmonary disease on chest radiograph, congestive cardiac failure (NYHA grade 3 or 4), history of demyelinating disease such as multiple sclerosis or optic neuritis).
- Bleeding disorder of the use of anti-coagulants
- Any known malignancy or a history of malignancy within the previous 5 years (with the exception of a basal cell carcinoma that has been treated with no evidence of recurrence).
- Any other contraindication to etanercept, methotrexate or parenteral depomedrone.
- Patients will also be excluded with the following laboratory results: haemoglobin <8.5 gm/dl, total white cell count <3.5 x 109/litre, serum transaminase value more than twice the upper limit of normal, and serum creatinine >150 micromoles/litre.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
University Hopsital Birmingham NHS Foundation Trust
Birmingham, West Midlands, B15 2TH
Paresh Jobanputra, MRCP MD, Paresh.Jobanputra@uhb.nhs.uk
Sandwell and West Birmingham Hospitals NHS Trust
Birmingham, West Midlands, B18 7QH
Karim Raza, MRCP PhD, k.raza@bham.ac.uk
About this study
Official title: Remission Induction in Very Early Rheumatoid Arthritis: a Comparison of Etanercept Plus Methotrexate Plus Steroid With Standard Therapy
Rheumatoid arthritis (RA) is a debilitating chronic immune mediated inflammatory disease which affects 1% of the European population. RA is associated with significant joint damage, disability and an enhanced mortality. Current treatment strategies target patients once synovitis has been present for several months and it is clear that the patient has developed persistent disease. After the first 3 months of symptoms, we and others have shown that the persistence of chronic inflammation in the rheumatoid synovium is driven by hyperplastic stromal tissue which inhibits leukocyte apoptosis leading to the accumulation of inflammatory cells in the joint. Therapies at this stage of disease, with conventional disease modifying anti-rheumatic drugs (DMARDs) as well as drugs targeting TNF-alpha reduce disease activity but are unable to cure RA. We have now identified that the very early phase of synovitis in patients destined to develop RA (within the first 12 weeks of symptoms) represents a pathologically distinct phase of disease. This suggests that late disease is not just more of early disease and gives, for the first time, a clear rationale for very early intervention. Building on these recent observations, we propose to test the hypothesis that the disease processes in the very early stages of RA are fundamentally different to those in established chronic disease. This will be done by assessing whether treatment during this phase with the well-established gold standard modality of anti-TNF-alpha therapy and methotrexate can permanently switch off inflammation, preventing the development of RA and thereby effecting a cure of the disease.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Etanercept, methotrexate and depomedrone, depemedrone
- Keywords
- Early arthritis, Rheumatoid arthritis, Rheumatoid factor, Anti CCP antibody, Remission, Anti-TNF therapy, methotrexate
- Medical subject headings
- Arthritis, Rheumatoid, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Etanercept, methotrexate and depomedroneDrug
Etanercept (50mg weekly; subcutaneous) Methotrexate (7.5-25mg weekly; oral) Depomedrone (up to 120mg; intraarticular / intramuscular)
depemedroneDrug
depomedrone (up to 120mg im/ia) methotrexate (added after symptoms have been present for 12 weeks)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Intensive therapy Receives: Drug: Etanercept, methotrexate and depomedrone |
| 2 | Active comparator | Standard therapy Receives: Drug: depemedrone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The percentage of patients in drug free clinical remission at week 48 having withdrawn therapy at week 24 i.e. the induction of drug free remission.
Measured: week 48
Secondary outcomes (6)
The percentage of patients in clinical remission at week 24 (when all drugs will be withdrawn if remission has been achieved).
Measured: week 24
The percentage of patients in radiological remission (no ultrasound evidence of synovitis) at week 24.
Measured: week 24
Clinical disease activity measures, including ACR responder rates (20%, 50%, and 70%), Disease Activity Score in 28 joints (DAS28), functional assessments (HAQ) and health status (EuroQuol-5D) at week 24.
Measured: week 24
The percentage of patients in drug free radiological remission (no ultrasound evidence of synovitis) at week 48 having withdrawn therapy at week 24.
Measured: week 48
Clinical disease activity measures, including ACR responder rates (20%, 50%, and 70%), Disease Activity Score in 28 joints (DAS28), functional assessments (HAQ) and health status (EuroQuol-5D) at weeks 48 and 96.
Measured: weeks 48 and 96.
The rate of progression of radiological change on conventional radiographs from baseline to week 48 and week 96.
Measured: weeks 48 and 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2007 (estimated)
- Study startSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Investigators
- Karim Raza, MRCP PhD, Principal investigator, University of BirminghamChristopher D Buckley, FRCP PhD, Study director, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00523692
- Sponsor's protocol ID
- RRK2939
- Other IDs
- REC reference 06/Q2404/95, EudraCT number 2006-001428-38, CTA number 16719/0201/001-0001
- Acronym
- RIVERA
- Status last verified
- Aug 2007
- First submitted
- 30 Aug 2007
- Last updated
- 31 Aug 2007
- Results posted
- No
- Data monitoring committee
- No
Publications
Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, Lord JM, Gordon C, Buckley CD, Salmon M. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther. 2005;7(4):R784-95. doi: 10.1186/ar1733. Epub 2005 Apr 7.
PubMed 15987480Raza K, Breese M, Nightingale P, Kumar K, Potter T, Carruthers DM, Situnayake D, Gordon C, Buckley CD, Salmon M, Kitas GD. Predictive value of antibodies to cyclic citrullinated peptide in patients with very early inflammatory arthritis. J Rheumatol. 2005 Feb;32(2):231-8.
PubMed 15693082Raza K, Buckley CE, Salmon M, Buckley CD. Treating very early rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2006 Oct;20(5):849-63. doi: 10.1016/j.berh.2006.05.005.
PubMed 16980210
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remission Induction in Very Early Rheumatoid Arthritis: a Comparison of Etanercept Plus Methotrexate Plus Steroid With Standard Therapy
- ClinicalTrials.gov ID
- NCT00523692
- Acronym / sponsor ID
- RIVERA / RRK2939
- Conditions
- Rheumatoid Arthritis
- Keywords
- Early arthritis, Rheumatoid arthritis, Rheumatoid factor, Anti CCP antibody, Remission, Anti-TNF therapy, methotrexate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Hospital BirminghamUniversity, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Study start
- Sep 2007
- First posted
- 31 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rheumatoid arthritis (RA) is a debilitating chronic immune mediated inflammatory disease which affects 1% of the European population. RA is associated with significant joint damage, disability and an enhanced mortality. Current treatment strategies target patients once synovitis has been present for several months and it is clear that the patient has developed persistent disease. After the first 3 months of symptoms, we and others have shown that the persistence of chronic inflammation in the rheumatoid synovium is driven by hyperplastic stromal tissue which inhibits leukocyte apoptosis leading to the accumulation of inflammatory cells in the joint. Therapies at this stage of disease, with conventional disease modifying anti-rheumatic drugs (DMARDs) as well as drugs targeting TNF-alpha reduce disease activity but are unable to cure RA. We have now identified that the very early phase of synovitis in patients destined to develop RA (within the first 12 weeks of symptoms) represents a pathologically distinct phase of disease. This suggests that late disease is not just more of early disease and gives, for the first time, a clear rationale for very early intervention. Building on these recent observations, we propose to test the hypothesis that the disease processes in the very early stages of RA are fundamentally different to those in established chronic disease. This will be done by assessing whether treatment during this phase with the well-established gold standard modality of anti-TNF-alpha therapy and methotrexate can permanently switch off inflammation, preventing the development of RA and thereby effecting a cure of the disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Etanercept, methotrexate and depomedroneIntensive therapy |
| 2 | Active comparator | Drug: depemedroneStandard therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age over 18 years
- Synovial swelling of at least 1 joint confirmed by clinical assessment
- Duration of symptoms attributable to inflammatory joint disease (pain, swelling or early morning stiffness of >1 hour) of < 12 weeks.
- Seropositivity for RF and anti-CCP Ab
- Women of childbearing potential or men capable of fathering children must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization) during the study.
Key exclusion criteria (13 listed)
- Previous history of inflammatory arthritis.
- Previous use of DMARDs or anti-TNF-agents.
- Any current inflammatory condition with signs or symptoms that might confound the diagnosis (e.g. connective tissue disorders).
- Clinical evidence of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to study entry.
- Administration, or expected administration, of any live virus or bacterial vaccination within 3 months before the first administration of study agent, or during the trial.
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 and depomedroneEtanercept (50mg weekly; subcutaneous) Methotrexate (7.5-25mg weekly; oral) Depomedrone (up to 120mg; intraarticular / intramuscular) | Drug | 1 |
| depemedronedepomedrone (up to 120mg im/ia) methotrexate (added after symptoms have been present for 12 weeks) | Drug | 2 |
Primary outcome
The percentage of patients in drug free clinical remission at week 48 having withdrawn therapy at week 24 i.e. the induction of drug free remission.
Time frame: week 48
6 secondary outcomes
The percentage of patients in clinical remission at week 24 (when all drugs will be withdrawn if remission has been achieved).
Time frame: week 24
The percentage of patients in radiological remission (no ultrasound evidence of synovitis) at week 24.
Time frame: week 24
Clinical disease activity measures, including ACR responder rates (20%, 50%, and 70%), Disease Activity Score in 28 joints (DAS28), functional assessments (HAQ) and health status (EuroQuol-5D) at week 24.
Time frame: week 24
The percentage of patients in drug free radiological remission (no ultrasound evidence of synovitis) at week 48 having withdrawn therapy at week 24.
Time frame: week 48
Clinical disease activity measures, including ACR responder rates (20%, 50%, and 70%), Disease Activity Score in 28 joints (DAS28), functional assessments (HAQ) and health status (EuroQuol-5D) at weeks 48 and 96.
Time frame: weeks 48 and 96.
The rate of progression of radiological change on conventional radiographs from baseline to week 48 and week 96.
Time frame: weeks 48 and 96
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2007.
- Background: PubMed 15987480Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, Lord JM, Gordon C, Buckley CD, Salmon M. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther. 2005;7(4):R784-95. doi: 10.1186/ar1733. Epub 2005 Apr 7.
- Background: PubMed 15693082Raza K, Breese M, Nightingale P, Kumar K, Potter T, Carruthers DM, Situnayake D, Gordon C, Buckley CD, Salmon M, Kitas GD. Predictive value of antibodies to cyclic citrullinated peptide in patients with very early inflammatory arthritis. J Rheumatol. 2005 Feb;32(2):231-8.
- Background: PubMed 16980210Raza K, Buckley CE, Salmon M, Buckley CD. Treating very early rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2006 Oct;20(5):849-63. doi: 10.1016/j.berh.2006.05.005.
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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.
Karim Raza, MRCP PhD principal investigator
University of Birmingham
Christopher D Buckley, FRCP PhD study director
University of Birmingham
2 sites 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, methotrexate and depomedrone and depemedrone in people with Rheumatoid Arthritis, run by University Hospital Birmingham at 2 sites in United Kingdom.
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 6 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 31 Aug 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Karim Raza, MRCP PhD (00 44 1214143837, k.raza@bham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The percentage of patients in drug free clinical remission at week 48 having withdrawn therapy at week 24 i.e. the induction of drug free remission. (time frame: week 48). 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 NCT00523692, which also lists 3 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 31 Aug 2007.