Clinical trial NCT02644499: Comparison of Combination Disease Modifying Antirheumatic Drugs With Methotrexate Therapy in Early Rheumatoid Arthritis
Official title: Comparison of Combination Disease Modifying Antirheumatic Drugs (DMARDs) With Single Drug (Methotrexate) Therapy in Early Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: Jawaharlal Institute of Postgraduate Medical Education & Research
Sponsor class: OTHER_GOV
First posted: 2015-12-31
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: A good response according to European league against rheumatism (EULAR) response criteria and Functional ability with Indian health assessment questionnaire (iHAQ)
timeFrame: 3 months
Secondary outcomes:
measure: Mean changes over time in early morning stiffness (EMS)
timeFrame: 3 months
measure: Mean changes over time in erythrocyte sedimentation rate (ESR)
timeFrame: 3 months
measure: Disease activity as per ultrasound (US-7) score
timeFrame: 3 months
measure: Radiographic progression assessed with Simple Erosion Narrowing Score (SENS)
timeFrame: 3 months
measure: Adverse drug reactions
timeFrame: 3 months
Other outcomes:
Locations:
city: Pondicherry
country: India
facility: Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER)
state: Pondicherry UT
Study officials:
affiliation: Jawaharlal Institute of Postgraduate Medical Education & Research
name: Vir S Negi, DM
role: PRINCIPAL_INVESTIGATOR
affiliation: Jawaharlal Institute of Postgraduate Medical Education & Research
name: Jignesh B Usdadiya, MD
role: STUDY_CHAIR
References: