Remission Induction in Very Early Rheumatoid Arthritis (RIVERA)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2007 by University Hospital Birmingham.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:
University Hospital Birmingham
ClinicalTrials.gov Identifier:
NCT00523692
First received: August 30, 2007
Last updated: NA
Last verified: August 2007
History: No changes posted
  Purpose

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 Intervention Phase
Rheumatoid Arthritis
Drug: Etanercept, methotrexate and depomedrone
Drug: depemedrone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (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

Resource links provided by NLM:


Further study details as provided by University Hospital Birmingham:

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. [ Time Frame: 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). [ 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 ]

Estimated Enrollment: 20
Study Start Date: September 2007
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00523692

Contacts
Contact: Karim Raza, MRCP PhD 00 44 1214143837 k.raza@bham.ac.uk

Locations
United Kingdom
Sandwell and West Birmingham Hospitals NHS Trust Not yet recruiting
Birmingham, West Midlands, United Kingdom, B18 7QH
Contact: Karim Raza, MRCP PhD       k.raza@bham.ac.uk   
University Hopsital Birmingham NHS Foundation Trust Not yet recruiting
Birmingham, West Midlands, United Kingdom, B15 2TH
Contact: Paresh Jobanputra, MRCP MD       Paresh.Jobanputra@uhb.nhs.uk   
Sponsors and Collaborators
University Hospital Birmingham
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Principal Investigator: Karim Raza, MRCP PhD University of Birmingham
Study Director: Christopher D Buckley, FRCP PhD University of Birmingham
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00523692     History of Changes
Other Study ID Numbers: RRK2939, REC reference 06/Q2404/95, EudraCT number 2006-001428-38, CTA number 16719/0201/001-0001
Study First Received: August 30, 2007
Last Updated: August 30, 2007
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University Hospital Birmingham:
Early arthritis
Rheumatoid arthritis
Rheumatoid factor
Anti CCP antibody
Remission
Anti-TNF therapy
methotrexate

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
TNFR-Fc fusion protein
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics

ClinicalTrials.gov processed this record on September 22, 2014