RIVERA: Remission Induction in Very Early Rheumatoid Arthritis

Sponsor

University Hospital Birmingham (Other)

Overall Status

Unknown status

CT.gov ID

NCT00523692

Collaborator

Wyeth is now a wholly owned subsidiary of Pfizer (Industry)

Enrollment

Locations

Arms

Patients Per Site

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Etanercept, methotrexate and depomedrone Drug: depemedrone	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Remission Induction in Very Early Rheumatoid Arthritis: a Comparison of Etanercept Plus Methotrexate Plus Steroid With Standard Therapy

Study Start Date :

Sep 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Intensive therapy	Drug: Etanercept, methotrexate and depomedrone Etanercept (50mg weekly; subcutaneous) Methotrexate (7.5-25mg weekly; oral) Depomedrone (up to 120mg; intraarticular / intramuscular)
Active Comparator: 2 Standard therapy	Drug: depemedrone depomedrone (up to 120mg im/ia) methotrexate (added after symptoms have been present for 12 weeks)

Arm

Intervention/Treatment

Experimental: 1

Intensive therapy

Drug: Etanercept, methotrexate and depomedrone

Etanercept (50mg weekly; subcutaneous) Methotrexate (7.5-25mg weekly; oral) Depomedrone (up to 120mg; intraarticular / intramuscular)

Active Comparator: 2

Standard therapy

Drug: depemedrone

depomedrone (up to 120mg im/ia) methotrexate (added after symptoms have been present for 12 weeks)

Outcome Measures

Primary Outcome Measures

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. [week 48]

Secondary Outcome Measures

The percentage of patients in clinical remission at week 24 (when all drugs will be withdrawn if remission has been achieved). [week 24]
The percentage of patients in radiological remission (no ultrasound evidence of synovitis) at week 24. [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. [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. [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. [weeks 48 and 96.]
The rate of progression of radiological change on conventional radiographs from baseline to week 48 and week 96. [weeks 48 and 96]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hopsital Birmingham NHS Foundation Trust	Birmingham	West Midlands	United Kingdom	B15 2TH
2	Sandwell and West Birmingham Hospitals NHS Trust	Birmingham	West Midlands	United Kingdom	B18 7QH