Optimized Treatment Algorithm for Patients With Early Rheumatoid Arthritis (RA)

Arthritis, Rheumatoid Clinical Trial

— OPERA  

Official title:

Optimized Treatment Algorithm in Early Rheumatoid Arthritis: Methotrexate and Intra-articular Glucocorticosteroid Plus Adalimumab or Placebo in the Treatment of Early Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00660647
• Other study ID #: VEK-20070008
• Status: Completed
• Phase: Phase 3
• First received: April 10, 2008
• Last updated: November 23, 2015
• Start date: September 2007
• Est. completion date: December 2011

Study information

• Verified date: November 2015
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: National Board of Health
• Study type: Interventional

Clinical Trial Summary

Optimized treatment algorithm in early rheumatoid arthritis:

Methotrexate and intra-articular glucocorticosteroid plus adalimumab or placebo in the treatment of early rheumatoid arthritis.

A Randomised, double-blind and placebo-controlled, two arms, parallel group study of the additive effect of adalimumab concerning inflammatory control and inhibition of erosive development.

Optimized Treatment Algorithms for Patients with Early RA

Description:

In newly diagnosed rheumatoid arthritis patients it is recommended to treat as soon as possible with methotrexate and steroids However, this treatment algorithm, will only bring one third of the patients into remission and cannot stop progressive, persistent joint damage. The possible benefits and risks of adding adalimumab to this conventional treatment algorithm is unknown.

The aim of the study is to clarify the possible benefits of adding adalimumab an anti-TNF-alfa inhibitor versus placebo to the treatment of rheumatoid arthritis patients, who are treated very early and given methotrexate and intraarticular triamcinolone hexacetonide. Efficacy will be evaluated by DAS 28, ACR 20/50/70, HAQ, progressive changes in X-ray, MRI and DXA-scans.

Adverse events will also be registered.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients (more than 18 years) with rheumatoid arthritis according to the ACR classification criteria (1) who have had the diagnose < 6 months.

2. Moderate to severe rheumatoid arthritis defined as DAS28 (CRP-based) > 3.2.

3. Negative pregnancy test (serum HCG) for women of childbearing potential prior to trial start. (Non-fertile women are defined as postmenopausal for at least 1 year or surgical sterilisation (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)). Fertile women included in the trial should use contraception during the entire trial period (i.e. one of the following methods: Oral contraception, intrauterine device (IUD), depot injection of progesterone, subdermal implantation, contraceptive vaginal ring, transdermal depot plaster). In addition, contraception should be used for a period of 150 days after any discontinuation of trial medicine.

4. Ability and willingness to inject the sc. injections him/herself or to have an assistant give the injections.

5. Ability and willingness to give written informed consent and to meet the requirements of the trial protocol.

Exclusion Criteria:

1. Persons with latent TB defined with a positive Mantoux test (>12 mm for vaccinated and 6 mm for non-vaccinated), positive cultivation of mycobacteria in tissue samples, chest X-ray indicating TB,or other risk factors for activation of untreated latent TB, and persons not been given adequate TB prophylaxis according to the instructions of the department.

2. Active or recurrent infections or severe infections requiring hospitalization or treatment with i.v. antibiotics within the last 30 days or oral antibiotics within the last 14 days prior to inclusion

3. Positive serology for Hepatitis B or C indicating active infection.

4. Medical history with a positive HIV status (Check of HIV test upon suspicion).

5. Medical history with histoplasmosis or listeriosis.

6. Previous cancer or lymph proliferative disease except cases teated radically and have been without relapse for a minimum of 5 years.

Patients with previous squamous cell carcinoma, basal cell skin carcinoma or cervical dysplasia, who have been treated successfully and radically can be included.

7. Previous diagnosis or signs of demyelinized disease in the CNS system (e.g. optic neuritis, visual disorder, disturbed gait, facial paralysis, apraxia).

8. Severe renal insufficiency (creatinine clearance < 35 ml/min - nomogram).

9. Affected liver function: Liver enzymes > 2 x above normal limit value.

10. Clinical significant drug or alcohol abuse during the past year and/or current daily alcohol consumption.

11. Unstable diabetes, unstable ischemic heart disease, heart insufficiency (NYHA III-IV), active chronic inflammatory intestinal disease, recent cerebral apoplexia (within 3 months), chronic leg ulcer or any other condition (e.g. kateter a demeure)which according to the investigator imposes an increased risk to the subject, if he/she participates in the protocol.

12. Anticoagulant therapy.

13. Pregnancy or breast-feeding.

14. Other inflammatory rheumatic diseases.

15. Aggressive parvovirus B19 infection.

16. Previous treatment with one or more DMARDs.

17. Glucocorticosteroid treatment within the last 4 weeks (except nasal and inhalation steroids).

18. Contraindications for trial medicine.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Adalimumab
Adalimumab injection 0.8 ml (40 mg) s.c. every second week in up to 2 years
• Placebo
Saline injection 0.9%, 0.8 ml s.c. every second week up to 2 years

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (4)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Abbott, Meda Pharmaceuticals

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients who achieve a DAS28 < 3.2		0, 1, 3, 6, 9, 12 and 24 months (DAS28)	No
Secondary	Changes in DAS28 from start of treatment		1, 3, 6, 9, 12 and 24 months	No