Back to results

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

Primary Purpose

Rheumatoid Arthritis

Status

Terminated

Phase

Phase 3

Locations

India

Study Type

Interventional

Intervention

Methotrexate

Leflunomide

Hydroxychloroquine

Prednisolone

Folic Acid

Sulfasalazine

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

group 1- MTX+LEF+HCQ

group 2- MTX+SSZ+HCQ

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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- Tender joint count 28 Swollen joint count 28 ESR Patient global assessment of health

Secondary Outcome Measures

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

Ultrasound 7 score (US-7) Calculates ultrasound score in 7 joints using greyscale and power doppler to evaluate for disease activity (synovitis, tenosynovitis) and damage (erosions) Score minimum value= 0 Maximum value = 108 Higher score indicates worse disease

Number of Participants With Adverse Drug Reactions

Infections, transaminitis, nausea, vomiting, derranged renal function tests etc

Indian Health Assessment Questionnaire (iHAQ)

Indian version of Health assessment Questionnaire (iHAQ) Comprises of 12 questions relating to functional activity iHAQ score ranges from 0 to 3 (minimum 0, maximum 3) Higher scores indicate more disability

Full Information

NCT ID

NCT02930343

First Posted

September 13, 2016

Last Updated

July 25, 2021

Sponsor

Jawaharlal Institute of Postgraduate Medical Education & Research

1. Study Identification

Unique Protocol Identification Number

NCT02930343

Brief Title

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

Official Title

Comparison of Sulfasalazine Versus Leflunomide Based Combination Disease Modifying Anti-rheumatic Drug Therapy (DMARD) in Patients With Rheumatoid Arthritis Failing Methotrexate Monotherapy : A Randomized Control Trial

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Terminated

Why Stopped

Due to time constraints, the study was halted prematurely

Study Start Date

September 2016 (Actual)

Primary Completion Date

August 2018 (Actual)

Study Completion Date

August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Jawaharlal Institute of Postgraduate Medical Education & Research

4. Oversight

Data Monitoring Committee

5. Study Description

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)

Detailed Description

Patients aged ≥18 years, fulfilling the 2010 ACR EULAR criteria for RA (symptom duration less than two years) , having more than 4 joints involved & having moderate to severe disease activity (DAS28≥3.2) will be invited to participate. After providing written informed consent, eligible patients will be first started on MTX monotherapy & only patients who have persistant moderate disease activity (DAS28 ESR > 3.2) will be randomized into two groups. Block randomization will be done to generate random allocation sequence Group 1 - will receive MTX+LEF+HCQ Group 2- will receive MTX+SSZ+HCQ DMARD dosages used are: MTX 25 mg/week orally (dosage after 6 weeks),SSZ 2g/d (after 4 weeks) LEF 20 mg/day (dosage after 2 weeks) and HCQ 200 mg/day. Glucocorticoids will be given in an oral tapering scheme. All patients will be prescribed folic acid (10 mg/week) during MTX prescription.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

136 (Actual)

8. Arms, Groups, and Interventions

Arm Title

group 1- MTX+LEF+HCQ

Arm Type

Active Comparator

Arm Description

Arm Title

group 2- MTX+SSZ+HCQ

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

folitrax, MTX

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Leflunomide

Other Intervention Name(s)

Arava, Lefno, LEF

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Hydroxychloroquine

Other Intervention Name(s)

HCQ

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Prednisolone

Other Intervention Name(s)

Steroids, Glucocorticoids

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

Folic Acid

Other Intervention Name(s)

Folvite

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Sulfasalazine

Other Intervention Name(s)

Saaz, SSZ

Intervention Description

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)

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

12 weeks

Title

Number of Participants With Adverse Drug Reactions

Description

Infections, transaminitis, nausea, vomiting, derranged renal function tests etc

Time Frame

24 weeks

Title

Indian Health Assessment Questionnaire (iHAQ)

Description

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vir S Negi, DM

Organizational Affiliation

Jawaharlal Institute of Postgraduate Medical Education & Research

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Pooja Belani, MD

Organizational Affiliation

Jawaharlal Institute of Postgraduate Medical Education & Research

Official's Role

Study Chair

Facility Information:

Facility Name

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

City

Pondicherry

ZIP/Postal Code

605006

Country

India

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34586472

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs