Clinical trial NCT02930343: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Jawaharlal Institute of Postgraduate Medical Education & Research
Sponsor class: OTHER_GOV
First posted: 2016-10-12
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Achieving Good EULAR Response at the End of 12 Weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Disease Activity as Per Ultrasound-7 (US-7) Score
timeFrame: 12 weeks
measure: Number of Participants With Adverse Drug Reactions
timeFrame: 24 weeks
measure: Indian Health Assessment Questionnaire (iHAQ)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Pondicherry
country: India
facility: Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research
Study officials:
affiliation: Jawaharlal Institute of Postgraduate Medical Education & Research
name: Vir S Negi, DM
role: PRINCIPAL_INVESTIGATOR
affiliation: Jawaharlal Institute of Postgraduate Medical Education & Research
name: Pooja Belani, MD
role: STUDY_CHAIR
References:
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.