Comparison of Disease Modifying Antirheumatic Drugs Therapy in Patients With RA Failing Methotrexate Monotherapy

NCT02930343 | Terminated Phase 3 Results

• 1 other identifier: JIP/IEC/2016/27/893
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

RA (Rheuatoid arthritis) is a multisystem disease that mainly involves joints resulting in destructive arthritis if not treated rapidly. Inspite of various advances in field of early diagnosis and treatment of RA, there is still a need for better understanding of the efficacy and safety of various combinations of conventional DMARDS, and to rank them in order accordingly, so as to give a clearer vision for further management of RA once MTX monotherapy fails, so as to achieve remission as soon as possible. The study will be conducted at the Department of Clinical Immunology, JIPMER (Jawaharlal Institute of Postgraduate Medical Education \& Research). patients who fail methotrexate monotherapy will be randomised to 2 treatment arms - either a combination of Sulfasalazine (SSZ), Hydroxychloroquine (HCQ) and Methotrexate (MTX) or Leflunomide (LEF), Hydroxychloroquine (HCQ) and Methotrexate (MTX)

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Number of Patients Achieving Good EULAR Response at the End of 12 Weeks

  EULAR response criteria for Rheumatoid arthritis includes- estimation of DAS 28 ESR, that includes- 1. Tender joint count 28 2. Swollen joint count 28 3. ESR 4. Patient global assessment of health

  12 weeks

Secondary Outcomes (3)

• Disease Activity as Per Ultrasound-7 (US-7) Score

  12 weeks

• Number of Participants With Adverse Drug Reactions

  24 weeks

• Indian Health Assessment Questionnaire (iHAQ)

  12 weeks

Study Arms (2)

group 1- MTX+LEF+HCQ

ACTIVE COMPARATOR

Active Comparator: 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: 7.5 mg/day, weeks 2-4: 5 mg/day, weeks 4-6: 5 mg on alternate day and then stop) will be given as bridging therapy.

Drug: Methotrexate; Drug: Leflunomide; Drug: Hydroxychloroquine; Drug: Prednisolone; Drug: Folic Acid

group 2- MTX+SSZ+HCQ

ACTIVE COMPARATOR

Combination of Methotrexate (up to 25 mg per week), Sulfasalazine (2g per 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: 7.5 mg/day, weeks 2-4: 5 mg/day, weeks 4-6: 5 mg on alternate day and then stop) will be given as bridging therapy.

Drug: Methotrexate; Drug: Hydroxychloroquine; Drug: Prednisolone; Drug: Folic Acid; Drug: Sulfasalazine

Interventions

Methotrexate DRUG

Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic diseases

Also known as: folitrax, MTX

group 1- MTX+LEF+HCQ; group 2- MTX+SSZ+HCQ

Leflunomide DRUG

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

Also known as: Arava, Lefno, LEF

group 1- MTX+LEF+HCQ

Hydroxychloroquine DRUG

Hydroxychloroquine (HCQ) is a well-tolerated DMARD that is commonly used in combination therapy regimens for RA. HCQ is more commonly used than chloroquine.

Also known as: HCQ

group 1- MTX+LEF+HCQ; group 2- MTX+SSZ+HCQ

Prednisolone DRUG

Low dose prednisolone (weeks 1-2: 7.5 mg/day, weeks 2-4: 5 mg/day, weeks 4-6: 5 mg on alternate day and then stop)

Also known as: Steroids, Glucocorticoids

group 1- MTX+LEF+HCQ; group 2- MTX+SSZ+HCQ

Folic Acid DRUG

Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.

Also known as: Folvite

group 1- MTX+LEF+HCQ; group 2- MTX+SSZ+HCQ

Sulfasalazine DRUG

5-aminosalicylic acid (5-ASA) is the active component of sulfasalazine; the specific mechanism of action of 5-ASA is unknown; however, it is thought that it modulates local chemical mediators of the inflammatory response, especially leukotrienes, and is also postulated to be a free radical scavenger or an inhibitor of tumor necrosis factor (TNF)

Also known as: Saaz, SSZ

group 2- MTX+SSZ+HCQ

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years satisfying ACR-EULAR criteria for RA
• Polyarthritis (\>4 joints)
• Disease duration of less than 2 years
• Patients with moderate to severe disease activity (DAS28\>3.2)
• Patients who have failed to respond to initial Methotrexate monotherapy

You may not qualify if:

• End stage disease (deformed fixed joints)
• Patients with vasculitis, extra-articular features like interstitial lung disease8
• 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), AST/ALT\>2× upper normal value and creatinine clearance \<30ml/minute )
• Pregnant, lactating women ; patients (both men and women) of reproductive age group unwilling for contraceptive use who have not completed the family
• Patients unable to come for regular follow up

Sponsors & Collaborators

• Jawaharlal Institute of Postgraduate Medical Education & Research: lead

Study Sites (1)

Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research

Puducherry, 605006, India

Location

Related Publications (1)

• Belani PJ, Kavadichanda CG, Negi VS. Comparison between leflunomide and sulfasalazine based triple therapy in methotrexate refractory rheumatoid arthritis: an open-label, non-inferiority randomized controlled trial. Rheumatol Int. 2022 May;42(5):771-782. doi: 10.1007/s00296-021-04994-1. Epub 2021 Sep 29.

  PMID: 34586472 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate; Leflunomide; Hydroxychloroquine; Prednisolone; Steroids; Glucocorticoids; Folic Acid; Sulfasalazine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Chloroquine; Aminoquinolines; Quinolines; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Limitations and Caveats

Early termination resulted in enrollment of 136 patients instead of 140 patients.

Results Point of Contact

• Title: Dr Pooja Belani
• Organization: JIPMER

drpoojabelani@gmail.com

8940482248

Study Officials

• Vir S Negi, DM

  Jawaharlal Institute of Postgraduate Medical Education & Research

  PRINCIPAL INVESTIGATOR

• Pooja Belani, MD

  Jawaharlal Institute of Postgraduate Medical Education & Research

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and head of the department, Department of Clinical Immunology

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: October 12, 2016
• Study Start: September 1, 2016
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: July 27, 2021
• Results First Posted: June 10, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)