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

September 28, 2019 updated by: Dr. Vir Singh Negi, Jawaharlal Institute of Postgraduate Medical Education & Research

Comparison of Combination Disease Modifying Antirheumatic Drugs (DMARDs) With Single Drug (Methotrexate) Therapy in Early Rheumatoid Arthritis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

186

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Pondicherry UT
      • Pondicherry, Pondicherry UT, India, 605006
        • Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
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
Other Names:
  • Arava, Lefno
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.
Other Names:
  • HCQ
Drug: Folic Acid
Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.
Other Names:
  • Folvite, Folate
Drug: Methotrexate
Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic dise
Other Names:
  • Folitrax, MTX
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)
Other Names:
  • Steroids, Glucocorticoids
Active Comparator: 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.
Drug: Folic Acid
Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.
Other Names:
  • Folvite, Folate
Drug: Methotrexate
Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic dise
Other Names:
  • Folitrax, MTX
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)
Other Names:
  • Steroids, Glucocorticoids

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
A good response according to European league against rheumatism (EULAR) response criteria and Functional ability with Indian health assessment questionnaire (iHAQ)
Time Frame: 3 months

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 Outcome Measures

Outcome Measure
Time Frame
Mean changes over time in early morning stiffness (EMS)
Time Frame: 3 months
3 months
Mean changes over time in erythrocyte sedimentation rate (ESR)
Time Frame: 3 months
3 months
Disease activity as per ultrasound (US-7) score
Time Frame: 3 months
3 months
Radiographic progression assessed with Simple Erosion Narrowing Score (SENS)
Time Frame: 3 months
3 months
Adverse drug reactions
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jawaharlal Institute of Postgraduate Medical Education & Research

Investigators

  • Principal Investigator: Vir S Negi, DM, Jawaharlal Institute of Postgraduate Medical Education & Research
  • Study Chair: Jignesh B Usdadiya, MD, Jawaharlal Institute of Postgraduate Medical Education & Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 31, 2015

Primary Completion (Actual)

February 17, 2017

Study Completion (Actual)

September 15, 2017

Study Registration Dates

First Submitted

December 30, 2015

First Submitted That Met QC Criteria

December 30, 2015

First Posted (Estimate)

December 31, 2015

Study Record Updates

Last Update Posted (Actual)

October 1, 2019

Last Update Submitted That Met QC Criteria

September 28, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JIP/IEC/SC/2013/5/433

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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