Optimal MTX Dose With Folic Acid Randomized Case-control Trial (MTXFARCT)

August 22, 2019 updated by: Gu Jieruo, Sun Yat-sen University

Safety and Efficacy of Optimal Methotrexate With Folic Acid in Patients With Rheumatoid Arthritis in Meizhou, Guangdong: a Randomized Case-control Study

This is an open, single-center, randomized,case controlled, prospective study. Previous studies in China lacked data of efficacy and safety of optimal methotrexate (MTX) dose with/without other anti-rheumatoid drugs (DMARDs) in the treatment of rheumatoid arthritis (RA) .Meanwhile there was no study on the optimal folic acid dose in aspect of preventing side effects of MTX. So we designed the experiment below.

The research planned to recruit 160 RA patients in Meizhou, Guangdong Province,China. The volunteers had no relief with 10 mg of MTX per week with/without other DMARDs for at least 3 month. They were randomly divided into 1:1 groups. The experimental group would be treated with original dMARDs ,incremental MTX( gradually increased to the optimal dose (0.3 mg/kg) in the first 12 weeks）and folic acid (the dose adjusted as appropriate with range from 5 mg to 90 mg per week) . While the control group would be treated with original MTX（10mg per week) and incremental original dMARDs( gradually increased to the maximum dose in the first 12 weeks). The two groups would keep the 12th week treatment last to the 36th week, and the efficacy and safety indexes would be evaluated during the whole study.

The objective of the study was to determine the efficacy and safety of the optimal dose of MTX in Chinese patients with rheumatoid arthritis, and to determine the efficacy and optimal prevention dose of folic acid in Chinese RA patients. It might be helpful for Chinese rheumatologists to use MTX accurately and efficiently to treat RA patients in clinical work.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

160

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

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510630
        • Recruiting
        • The 3rd affiliated hospital of Sun Yat-sen University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Dong Fang Lin, Doctor
        • Sub-Investigator:
          • Qi Yun Chen, Master
        • Sub-Investigator:
          • Yi Quan Wen, Master
        • Sub-Investigator:
          • Yan Li Zhang, Doctor
        • Sub-Investigator:
          • Xu Li Song, Bachelor
        • Sub-Investigator:
          • Qing Lv, Doctor
        • Sub-Investigator:
          • Xiqing Luo, Bachelor
        • Sub-Investigator:
          • Yun Feng Pan, Master

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 to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. According to the revised 1987 American Academy of Rheumatology (ACR) RA classification criteria, subjects must be diagnosed as rheumatoid arthritis ≥6 months.
  2. MTX was given 10 mg/week（not the maximum dose of MTX (calculated as 0.3 mg/kg)) for ≥3 months before admission.
  3. At the screening and baseline phases, the number of swollen joints (SJC) should be ≥1 (counting 66 joints), and the number of tender joints (TJC) should be ≥ 1 (counting 66 joints); the ESR should be ≥20 mm/h, and/or the CRP should be ≥ 10 mg/l;
  4. The age of the subjects ranged from 18 to 70 years.
  5. The following RA drugs can be used in combination within 3 months before admission; oral glucocorticoid (prednisone ≤10 mg/d or its equivalent), non-steroidal anti-inflammatory drugs (≤ the maximum recommended dose), leflunomide, hydroxychloroquine, sulfasalazine, total paeoniflorin, Tripterygium glycoside, azathioprine, and MTX. The stable dose of DMARDs should be at least 4 weeks before baseline, and the combined dose of DMARDs beside MTX could not reach the full dose.
  6. Women of childbearing age should agree to take effective contraceptive measures during the trial period;
  7. The urinary pregnancy test of women of childbearing age was negative at screening time.
  8. Understand the steps and contents of the experiment and sign the informed consent to participate in the experiment.

Exclusion Criteria:

  1. Those who underwent major surgery (including joint surgery) within 8 weeks before screening or who planned major surgery within 6 months after random selection;
  2. Patients with autoimmune diseases except RA include SLE, MCTD, scleroderma and polymyositis. But subjects with RA and secondary Sjogren syndrome were allowed to participate in the trial.
  3. Inflammatory arthritis (such as gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) .
  4. Intra-articular injection or other injection of corticosteroids within 4 weeks before baseline;
  5. Those who had been vaccinated with live/inactivated vaccine within 4 weeks before baseline;
  6. Three months before admission, the following drugs were used: cyclophosphamide, biological agents and folic acid.
  7. DMARDs dose reached maximum dosage in 3 months before admission， or DMARDs≥3 were used in 3 months before admission
  8. Subjects with severe uncontrolled diseases including cardiovascular disease, nervous system disease, pulmonary disease (including obstructive pulmonary disease and interstitial lung disease), nephropathy, liver disease, endocrine disease (including uncontrolled diabetes mellitus) and gastrointestinal diseases;
  9. known history of active or recurrent bacterial, viral, fungal, Mycobacterium or other infections (including, but not limited to, tuberculosis and atypical mycobacterium diseases, chest X-rays showing granulomatous diseases, hepatitis B and C, HIV infection, herpes zoster, but excluding Onychomycosis) ，any infection requiring hospitalization and intravenous antibiotic therapy within 4 weeks before screening ，or oral antibiotic therapy within 2 weeks before screening; active hepatitis B refers to HBsAg-positive patients without antiviral drugs and HBV-DNA > 10^4; active hepatitis C refers to anti-HCV-positive patients without antiviral drugs and HCV-RNA > 10^4;
  10. Subjects with a history of malignant tumors, including solid tumors and hematological malignancies (except excised or cured skin basal cell carcinomas);
  11. Pregnant or lactating women (breastfeeding);
  12. Subjects with neuropathy and other painful diseases may interfere with pain assessment.
  13. Serum creatinine > 1.5 mg/dl (equivalent to 133 umol/L);
  14. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times of the upper limit of normal value (if ALT or AST is greater than 2 times of the upper limit of normal value for the first time, it should be sampled again during the screening period), or total bilirubin is greater than the upper limit of normal value (if total bilirubin is greater than the upper limit of normal value for the first time at the screening, sampling should be done again during the selection period).
  15. Platelet count < 100 x 10^9/L, or white blood cells < 3 x 10^9/L;

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
Experimental: MTX group with folic acid
the group with optimal MTX dose (gradually increased from 0 to 12weeks，appropriate folic acid，and stable original other DMARDs
Drug: MTX
MTX group would be intervened by incremental MTX and folic acid，while the control group would be intervened by incremental original DMARDs they already used（including Leflunomide，Hydroxychloroquine,Sulfasalazine,Azathioprine,Tripterygium glycosides and Total glucosides of paeony)
Drug: Folic Acid
MTX group would be intervened by folic acid，while the control group would be not intervened by folic acid
Drug: DMARDs
including Leflunomide，Hydroxychloroquine,Sulfasalazine,Azathioprine,Tripterygium glycosides and Total glucosides of paeony
Active Comparator: control group without folic acid
the group with stable MTX 10mg/w dose and maximum DMARDs doses（graduallly increased from 0 to 12 weeks）without folic acid
Drug: MTX
MTX group would be intervened by incremental MTX and folic acid，while the control group would be intervened by incremental original DMARDs they already used（including Leflunomide，Hydroxychloroquine,Sulfasalazine,Azathioprine,Tripterygium glycosides and Total glucosides of paeony)
Drug: DMARDs
including Leflunomide，Hydroxychloroquine,Sulfasalazine,Azathioprine,Tripterygium glycosides and Total glucosides of paeony

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The response rate of ACR20 at the 36th weeks
Time Frame: at the 36th weeks
at the 36th weeks

Collaborators and Investigators

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

Sponsor

Sun Yat-sen University

Collaborators

Shanghai Pharmaceuticals Holding Co., Ltd

Investigators

  • Study Director: Yun Feng Pan, Master, the 3rd Hospital of Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 1, 2018

Primary Completion (Anticipated)

July 30, 2020

Study Completion (Anticipated)

July 30, 2020

Study Registration Dates

First Submitted

December 11, 2018

First Submitted That Met QC Criteria

August 22, 2019

First Posted (Actual)

August 26, 2019

Study Record Updates

Last Update Posted (Actual)

August 26, 2019

Last Update Submitted That Met QC Criteria

August 22, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • QHJH201805

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

No plan to share.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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