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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02930343
• Other study ID #: JIP/IEC/2016/27/893
• Status: Terminated
• Phase: Phase 3
• Start date: September 2016
• Est. completion date: August 2018

Study information

• Verified date: July 2021
• Source: Jawaharlal Institute of Postgraduate Medical Education & Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 136
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Age >18 years satisfying ACR-EULAR criteria for RA

1. Polyarthritis (>4 joints)

2. Disease duration of less than 2 years

3. Patients with moderate to severe disease activity (DAS28>3.2)

4. Patients who have failed to respond to initial Methotrexate monotherapy

Exclusion Criteria:

1. End stage disease (deformed fixed joints)

2. Patients with vasculitis, extra-articular features like interstitial lung disease8

3. 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 )

4. Pregnant, lactating women ; patients (both men and women) of reproductive age group unwilling for contraceptive use who have not completed the family

5. Patients unable to come for regular follow up

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Methotrexate
Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic diseases
• Leflunomide
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
• Hydroxychloroquine
Hydroxychloroquine (HCQ) is a well-tolerated DMARD that is commonly used in combination therapy regimens for RA. HCQ is more commonly used than chloroquine.
• Prednisolone
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)
• Folic Acid
Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.
• Sulfasalazine
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)

Locations

Country	Name	City	State
India	Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research	Pondicherry

Sponsors (1)

Lead Sponsor	Collaborator
Jawaharlal Institute of Postgraduate Medical Education & Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	12 weeks
Secondary	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	12 weeks
Secondary	Number of Participants With Adverse Drug Reactions	Infections, transaminitis, nausea, vomiting, derranged renal function tests etc	24 weeks
Secondary	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	12 weeks