| CTRI Number |
CTRI/2025/08/093231 [Registered on: 19/08/2025] Trial Registered Prospectively |
| Last Modified On: |
07/05/2026 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Comparison of efficacy, safety and Methotrexate poly glutamate levels (active form of methotrexate) between two different oral methotrexate regimens commonly used in treatment of Rheumatoid Arthritis. |
|
Scientific Title of Study
|
Comparison of efficacy and side effect profile of same day s[lit versus twice a week split of oral methotrexate in Rheumatoid Arthritis and comparison of Methotrexate poly glutamate levels in both groups: A randomised controlled study. |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Rajat Gupta |
| Designation |
Senior Resident |
| Affiliation |
King George Medical University |
| Address |
Department of Clinical Immunology and Rheumatology, KGMU
Lucknow
Lucknow
UTTAR PRADESH
226018
India |
| Phone |
919871735023 |
| Fax |
|
| Email |
drrajatgupta23@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Urmila Dhakad |
| Designation |
Professor |
| Affiliation |
King George Medical University |
| Address |
Department of Clinical Immunology and Rheumatology, KGMU
Lucknow
Lucknow
UTTAR PRADESH
226018
India |
| Phone |
919696349671 |
| Fax |
|
| Email |
drurmiladhakad@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Urmila Dhakad |
| Designation |
Professor |
| Affiliation |
King George Medical University |
| Address |
Department of Clinical Immunology and Rheumatology, KGMU
Lucknow
Lucknow
UTTAR PRADESH
226018
India |
| Phone |
919696349671 |
| Fax |
|
| Email |
drurmiladhakad@gmail.com |
|
|
Source of Monetary or Material Support
|
| King George Medical University
Shah Mina Road, Chowk, Lucknow, Uttar Pradesh, 226003, India |
|
|
Primary Sponsor
|
| Name |
King George Medical University |
| Address |
Qaisar Bagh, Lucknow, 226018 |
| Type of Sponsor |
Government medical college |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Rajat Gupta |
Department of Clinical Immunology and Rheumatology |
Room 11-15, Outpatient Department, Department of Clinical Immunology and Rheumatology, King George Medical University, Qaisar Bagh, Lucknow, 226018
Lucknow
UTTAR PRADESH |
919871735023
drrajatgupta23@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| King George Medical University, UP, Institutional Ethics Committee- Lucknow |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: M05||Rheumatoid arthritis with rheumatoid factor, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Methotrexate split dose in one day |
Same day split of oral methotrexate , 12 hours apart and will be followed for 6 months |
| Intervention |
Methotrexate split dose twice weekly |
This group will split oral methotrexate on 2 days in a week (Monday and Thursday) and will be followed for 6 months |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
1) Patients fulfilling ACR/EULAR 2010 criteria of Rheumatoid Arthritis and having moderate disease activity, which is defined by DAS28 more than 3.2
2) Patients who are more than or equal to 18 years old
3) Patients taking oral methotrexate for at least 1 month prior to inclusion in this study
4) Giving consent for participation in the study.
5) Methotrexate dose 15mg/week
6) Not on other conventional synthetic or biological DMARDs except HCQ (400mg/day) or low dose prednisolone (7.5 mg/day)
|
|
| ExclusionCriteria |
| Details |
Patients having significant cytopenias Anemia (Hb less than 6 g/dl), thrombocytopenia (platelet count less than 1 ×105/mm3), leukopenia (less than 3000/mm3), ALT/AST more than 80 IU or serum creatinine more than 1.5 mg/dl.
2) Contraindications to methotrexate, which are severe renal, pulmonary and liver disease, pre- existing bone marrow suppression, alcoholic liver disease, pregnancy, breastfeeding or patients planning conception, acute or chronic HBV or HCV infection
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To assess methotrexate polyglutamate levels and compare its levels between the two groups at Baseline, 3 and 6 months and change in disease severity measures (SDAI, CDAI and DAS28) at 24 weeks compared to baseline and side effect profile (symptomatic & labs) at 24 weeks |
1, 3 and 6 months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. To assess and compare Mean Glucocorticoid dose and NSAID score at 24 weeks between the two groups
2. To assess and compare Methotrexate intolerance severity score at 24 weeks between the two groups.
|
1, 3 and 6 months |
|
|
Target Sample Size
|
Total Sample Size="60"
Sample Size from India="60"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
01/10/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="3"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Methotrexate is a disease modifying anti-rheumatoid drug (DMARD) and an anchor drug used for treatment of Rheumatoid arthritis. Methotrexate is transformed in human body into its active metabolite, polyglutamate, whose half-life is 3 days. Anti-inflammatory effect is due to active form of methotrexate. Depending on the number of conjugated glutamates, MTX-PG may be present as MTX-PG1-5 or the longer chain MTX-PG (MTX-PG3-5) which is considered to be more active. MTX-PG3 is the most dominant and stable type of MTX-PG and could reflect the overall polyglutamate status. Studies show 28% higher bioavailability obtained when methotrexate dose is split and given 12 hours apart compared to single oral dose, resulting in superior efficacy. There are two methods of splitting methotrexate dose which are used commonly by rheumatologists across India. One is splitting dose in 2 days in a week, other is splitting methotrexate dose in a same day, 12 hours apart (morning and evening) Rationale Of the Study: To look for any difference in methotrexate polyglutamate levels, efficacy, side effect profile in same day spilt and twice a week split of oral methotrexate in Rheumatoid Arthritis patients, as there is a lack of literature in this comparison |