Study of Different Doses of Folic Acid in Combination With Methotrexate in Rheumatoid Arthritis (FOLVARI)
Introduction: Methotrexate is the sheet anchor for the treatment of rheumatoid arthritis. Folic acid supplementation is usually given at a dose of 5-30 mg per week to ameliorate adverse effects. Patients at our center are usually on the higher dose. However, it is unclear if higher doses are required, recent international recommendations suggest 5-10 mg per week only.
Objectives: To randomize rheumatoid patients being being started on Methotrexate into 2 groups- one on 5mg for 6 days a week (30mg per week) of folic acid and the other 5 mg twice a week (10 mg per week) for 24weeks. To look at difference in
Adverse effects due to methotrexate
a. Minor adverse effects: By symptom chart
a. Major adverse effects: Cytopenia (predefined) and transaminitis.
- Disease activity using Disease activity score 28 joints (3 variable) and functional status by health assessment questionnaire
- RBC folic acid levels Methodology: Randomised controlled trial, double blinded, placebo controlled. Sample size 50 in each group. One group of patients will receive folic acid 5 mg twice a week with placebo for 4 days and the other group will receive folic acid 5 mg 6 days a week for 24 weeks.
Patients will be administered adverse effects proforma, assessed for having cytopenias and transaminitis (pre defined) and disease activity will be calculated at every visit, ie., in the beginning at then at 8,16 and 24 weeks. In addition will look at the functional status and RBC folate levels at 0 and 24 weeks. Statistical analysis using chi-square test for proportions and t test for continuous variables.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Randomized Trial of 10 mg Versus 30 mg Per Week of Folic Acid in Combination With Methotrexate in Rheumatoid Arthritis|
- Adverse effects [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
i. Minor: Two Symptom charts: Those AEs related temporally to methotrexate and those not temporally related.
ii. Major: Hemoglobin (Hb), Platelet, Total leucocyte count or white blood count (TLC), Differential leukocyte count (DLC), Serum glutamic oxaloacetate transaminase (SGOT)/ serum glutamic pyruvate transaminase (SGPT) will be done at 3 months. Patients having Hb≤6, TLC ≤ 3500, Platelet ≤99000, SGOT or SGPT ≥80 IU/L
- disease activity [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]Using disease activity score 28 joints 3 variables(DAS 28-3v) : uses evaluation of tender joint count (TJC28), Swollen joint count (SJC28) and the erythrocyte sedimentation rate (ESR) using Westergren method.
- RBC folic acid: [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]This will be done by chemiluminescence assay, to compare folic acid levels at baseline and at 24 weeks
- Function [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]Look at the function by Indian Health assessment questionnaire
|Study Start Date:||April 2012|
|Study Completion Date:||December 2013|
|Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Folic acid 30 mg per week
Patients will be administered 5 mg folic acid for 6 days a week, no tablet on the day they take methotrexate (5 mg x 6 days = 30 mg per week)
Drug: Folic Acid
Folic acid tablets 5 mg
Active Comparator: Folic acid 10 mg
Patients will be given folic acid 5 mg for two days per week and placebo tablets for four days a week, no tablet on the day they take methotrexate (Folic acid 5mg x 2 days = 10mg per week)
Drug: Folic Acid
Folic acid tablets 5 mgDrug: Placebo
Matched placebo to folic acid 5 mg tables, to be given for 4 days a week
THIS TRIAL WILL INCLUDE NEW RHEUMATOID ARTHRITIS PATIENTS These patients will then be randomized into two groups - one which continues to take the same folic acid dose and one which is shifted to folic acid 10 mg per week.
|New OPD, #3035, Level 3, Rheumatology Clinic, Tuesday and Friday|
|Chandigarh, India, 160012|
|Principal Investigator:||Varun Dhir, MD, DM||PGIMER, Chandigarh, India|