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

NCT02644499 | Completed Phase 4

• 1 other identifier: JIP/IEC/SC/2013/5/433
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• A good response according to European league against rheumatism (EULAR) response criteria and Functional ability with Indian health assessment questionnaire (iHAQ)

  A good response is defined as a decrease after randomization of disease activity score- 28 joints (DAS28) score by \>1.2, and a resulting DAS28 score ≤ 3.2. Indian version of HAQ (iHAQ) has been validated in patients with RA, which comprises 12 questions (nine basic and three advanced activity of daily living) relevant to the Indian population. For each question there is a four-level difficulty scale ranging from 0 to 3 that represent no difficulty ('0'), some difficulty ('1'), much difficulty ('2'), and inability to do ('3'). The final score is the mean of the highest scores across the eight categories and ranges from 0 to 3, with higher levels indicating more disability.

  3 months

Secondary Outcomes (5)

• Mean changes over time in early morning stiffness (EMS)

  3 months

• Mean changes over time in erythrocyte sedimentation rate (ESR)

  3 months

• Disease activity as per ultrasound (US-7) score

  3 months

• Radiographic progression assessed with Simple Erosion Narrowing Score (SENS)

  3 months

• Adverse drug reactions

  3 months

Study Arms (2)

Combination therapy

ACTIVE COMPARATOR

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.

Drug: Methotrexate; Drug: Leflunomide; Drug: Hydroxychloroquine; Drug: Prednisolone; Drug: Folic Acid

Monotherapy

ACTIVE COMPARATOR

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.

Drug: Methotrexate; Drug: Prednisolone; Drug: Folic Acid

Interventions

Methotrexate DRUG

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

Also known as: Folitrax, MTX

Combination therapy; Monotherapy

Leflunomide 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

Also known as: Arava, Lefno

Combination therapy

Hydroxychloroquine 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.

Also known as: HCQ

Combination therapy

Prednisolone 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)

Also known as: Steroids, Glucocorticoids

Combination therapy; Monotherapy

Folic Acid DRUG

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

Also known as: Folvite, Folate

Combination therapy; Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years satisfying 2010 ACR (American college of rheumatology) - EULAR criteria for RA
• Arthritis in one or more joint (s)
• Symptom duration \<1 year
• DMARD naive
• Patients with moderate to severe disease activity (DAS28 ≥3.2)

You may not qualify if:

• Disease in Remission/inactive disease (DAS28 criteria)
• End stage disease (deformed fixed joints)
• Patients with vasculitis or other severe extra-articular features
• 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 )
• Pregnant, lactating females or inadequate contraception
• Patients unable to come for regular follow up

Sponsors & Collaborators

• Jawaharlal Institute of Postgraduate Medical Education & Research: lead

Study Sites (1)

Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER)

Puducherry, Pondicherry UT, 605006, India

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate; Leflunomide; Hydroxychloroquine; Prednisolone; Steroids; Glucocorticoids; Folic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Chloroquine; Aminoquinolines; Quinolines; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Vir S Negi, DM

  Jawaharlal Institute of Postgraduate Medical Education & Research

  PRINCIPAL INVESTIGATOR

• Jignesh B Usdadiya, MD

  Jawaharlal Institute of Postgraduate Medical Education & Research

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and head of the department, Department of Clinical Immunology

Study Record Dates

• First Submitted: December 30, 2015
• First Posted: December 31, 2015
• Study Start: December 31, 2015
• Primary Completion: February 17, 2017
• Study Completion: September 15, 2017
• Last Updated: October 1, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)