Comparison of Combination Disease Modifying Antirheumatic Drugs With Methotrexate Therapy in Early Rheumatoid Arthritis

NCT ID: NCT02644499

Last Updated: 2019-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 186 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2017-09-15

Brief Summary

This study will be conducted to find out how well a patient of rheumatoid arthritis (RA) will respond to disease-modifying antirheumatic drugs (DMARDs). RA is a chronic inflammatory arthritis, which leads to joint damage & disability if not treated properly. A DMARD is used to treat RA that slows down or prevents joint damage, as opposed to just relieve pain or inflammation by painkillers. The study will be conducted at the Department of Clinical Immunology, JIPMER (Jawaharlal Institute of Postgraduate Medical Education & Research). Patients will receive either a single DMARD (Methotrexate) or combination DMARDs therapy (Methotrexate + Leflunomide + Hydroxychloroquine). During treatment course, routine blood investigations will be carried out to monitor treatment response and side effects.

Detailed Description

Patients aged ≥18 years, fulfilling the 2010 ACR EULAR criteria for RA (symptom duration less than one year) & having moderate to severe disease activity (DAS28≥3.2) will be invited to participate. After providing written informed consent, eligible patients will be stratified into two groups. Block randomization will be done to generate random allocation sequence.

Treatment Group I will be treated with Methotrexate (MTX) monotherapy and Treatment Group II will be treated with Methotrexate + Leflunomide (LEF) + Hydroxychloroquine (HCQ) combination therapy. Concurrent treatment with non-steroidal anti-inflammatory drugs in adequate dose and oral low dose Glucocorticoids (GC) (max: 15 mg/d) will be allowed during the study.

DMARD dosages used are: MTX 25 mg/week orally (dosage after 6 weeks), LEF 20 mg/day (dosage after 2 weeks) and HCQ 400 mg/day. GCs will be given in an oral tapering scheme. All patients will be prescribed folic acid (10 mg/week) during MTX prescription.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination therapy

Combination of Methotrexate (up to 25 mg per week), Leflunomide (20 mg once a day) and Hydroxychloroquine (200-400 mg once at night). All drugs are to be taken orally. Duration of therapy is for 3 months. All patients will receive folic acid (5 mg twice a week) along with methotrexate. Low dose prednisolone (weeks 1-2: 15 mg/day, weeks 2-4: 10 mg/day, weeks 4-6: 5 mg/day and weeks 6-8: 2.5 mg/day then stop) will be given as bridging therapy.

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic dise

Leflunomide

Intervention Type: DRUG

Leflunomide inhibits pyrimidine synthesis, resulting in blockade of T-cell proliferation. Leflunomide is used in patients with moderate to severe active rheumatoid arthritis with early or late disease

Hydroxychloroquine

Intervention Type: DRUG

Hydroxychloroquine (HCQ) is a well-tolerated DMARD that is commonly used in combination therapy regimens for RA. HCQ is more commonly used than chloroquine.

Prednisolone

Intervention Type: DRUG

Low dose prednisolone (weeks 1-2: 15 mg/day, weeks 2-4: 10 mg/day, weeks 4-6: 5 mg/day and weeks 6-8: 2.5 mg/day then stop)

Folic Acid

Intervention Type: DRUG

Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.

Monotherapy

Methotrexate (up to 25 mg once a week) for 3 months. All patients will receive folic acid (5 mg twice a week) along with methotrexate. Low dose prednisolone (weeks 1-2: 15 mg/day, weeks 2-4: 10 mg/day, weeks 4-6: 5 mg/day and weeks 6-8: 2.5 mg/day then stop) will be given as bridging therapy.

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic dise

Prednisolone

Intervention Type: DRUG

Low dose prednisolone (weeks 1-2: 15 mg/day, weeks 2-4: 10 mg/day, weeks 4-6: 5 mg/day and weeks 6-8: 2.5 mg/day then stop)

Folic Acid

Intervention Type: DRUG

Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.

Interventions

Methotrexate

Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic dise

Intervention Type: DRUG

Leflunomide

Leflunomide inhibits pyrimidine synthesis, resulting in blockade of T-cell proliferation. Leflunomide is used in patients with moderate to severe active rheumatoid arthritis with early or late disease

Intervention Type: DRUG

Hydroxychloroquine

Hydroxychloroquine (HCQ) is a well-tolerated DMARD that is commonly used in combination therapy regimens for RA. HCQ is more commonly used than chloroquine.

Intervention Type: DRUG

Prednisolone

Low dose prednisolone (weeks 1-2: 15 mg/day, weeks 2-4: 10 mg/day, weeks 4-6: 5 mg/day and weeks 6-8: 2.5 mg/day then stop)

Intervention Type: DRUG

Folic Acid

Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.

Intervention Type: DRUG

Other Intervention Names

Folitrax, MTX; Arava, Lefno; HCQ; Steroids, Glucocorticoids; Folvite, Folate

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years satisfying 2010 ACR (American college of rheumatology) - EULAR criteria for RA

2. Arthritis in one or more joint (s)

3. Symptom duration <1 year

4. DMARD naive

5. Patients with moderate to severe disease activity (DAS28 ≥3.2)

Exclusion Criteria

1. Disease in Remission/inactive disease (DAS28 criteria)

2. End stage disease (deformed fixed joints)

3. Patients with vasculitis or other severe extra-articular features

4. Contraindications to DMARD therapy (Chronic Alcoholism, Chronic liver disease, Evidence of acute/chronic infection, Chronic kidney disease, Patients with leucopenia (<3.0×109/l), thrombocytopenia (<150×109/l), aspartate aminotransferase (AST)/alanine aminotransferase (ALT)>2× upper normal value and creatinine level >150 μmol/l )

5. Pregnant, lactating females or inadequate contraception

6. Patients unable to come for regular follow up

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jawaharlal Institute of Postgraduate Medical Education & Research

OTHER_GOV

Sponsor Role: lead

Responsible Party

Dr. Vir Singh Negi

Professor and head of the department, Department of Clinical Immunology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vir S Negi, DM

Role: PRINCIPAL_INVESTIGATOR

Jawaharlal Institute of Postgraduate Medical Education & Research

Jignesh B Usdadiya, MD

Role: STUDY_CHAIR

Jawaharlal Institute of Postgraduate Medical Education & Research

Locations

Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER)

Puducherry, Pondicherry UT, India

Countries

India

Other Identifiers

JIP/IEC/SC/2013/5/433

Identifier Type: -

Identifier Source: org_study_id