Study of Two Different Starting Doses of Methotrexate When Starting Treatment in Rheumatoid Arthritis (DMIRA)

Randomized Controlled Trial of Two Different Starting Doses of Methotrexate in Rheumatoid Arthritis

To use different starting doses of methotrexate (7.5 mg per week) versus 15 mg per week in patients with rheumatoid arthritis, followed by similar hiking up of dose (2.5 mg per 2 weeks, till max of 25 mg per week). To look at the effect on efficacy ( or speed of efficacy) versus the adverse effects.

Hypothesis: There will be no difference in the adverse effects, but better and faster control of disease when starting with a higher methotrexate dose

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Methotrexate

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • New OPD Block, Rheumatology Clinic, Level 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with rheumatoid arthritis fulfilling the ACR 1987 criteria
• Between 18 years to 65 year of age
• Having active disease Disease activity score (28 joints) DAS28-3 more than 5.1
• Not on methotrexate in the last 2 months
• Permitted to be on corticosteroids if the dosages stable for at least 1 weeks before randomization and if corticosteroid dosage less than 10 mg/day
• Permitted to be on other disease modifying anti-rheumatic drug (DMARD) like sulfasalazine, leflunomide and hydroxychloroquine, if dosages stable for at least 2 weeks before randomization

Exclusion Criteria:

• Pregnant/Breastfeeding
• Ongoing/Recent treatment with methotrexate (2 months)
• Chronic liver disease
• Renal failure
• Any leucopenia or thrombocytopenia
• Breast-feeding
• Desirous of pregnancy in the next 6 months
• Known Hepatitis B or C positive
• Known clinically relevant chronic lung disease: ILD
• Tuberculosis or other active infections
• Known HIV positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methotrexate 7.5 mg per week	Drug: Methotrexate; Different doses for both arms followed by similar escalation (2.5 mg every 15 d) till max of 25 mg per week or 3 months completed; Other Names: MEXATE
Experimental: Methotrexate 15 mg per week	Drug: Methotrexate; Different doses for both arms followed by similar escalation (2.5 mg every 15 d) till max of 25 mg per week or 3 months completed; Other Names: MEXATE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in the DAS28-3 (Disease Activity Score Using 28 Joints and Using 3 Variables) - Difference Between This Score at 12 Weeks and This Score at Baseline	DAS28-3 is disease activity score using 28 joints and using 3 variables (tender and swollen joint count for 28 joints and ESR(westergren 1st hour) It ranges from 0 to 9.3 where a lower value implies lower disease activity	12 weeks
Patients With Good Response (Final DAS28-3 Less Than 3.2 and Fall More Than 1.2)		3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Patients Who Withdrew Because of Any Cause	3 months
Proportion Requiring Stoppage/Decrease/Inability to Hike MTX Due to Cytopenia or Transaminitis (SGOT or SGPT More Than 80IU)	3 months
Proportion Who Withdrew Due to Intolerance	3 months

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research

Publications and helpful links

General Publications

• Dhir V, Singla M, Gupta N, Goyal P, Sagar V, Sharma A, Khanna S, Singh S. Randomized controlled trial comparing 2 different starting doses of methotrexate in rheumatoid arthritis. Clin Ther. 2014 Jul 1;36(7):1005-15. doi: 10.1016/j.clinthera.2014.05.063. Epub 2014 Jun 26.

Helpful Links

• published manuscript

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: July 26, 2011
• First Submitted That Met QC Criteria: July 27, 2011
• First Posted (Estimate): July 28, 2011

Study Record Updates

• Last Update Posted (Estimate): September 16, 2014
• Last Update Submitted That Met QC Criteria: September 5, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis; Active
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: NKG/992