Leflunomide Versus Sulfasalazine/Methotrexate in Rheumatoid Arthritis:an Ultrasound/Magnetic Resonance Imaging Study

NCT01659242 | Terminated Phase 4

• 1 other identifier: YK 01-2012
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

In rheumatoid arthritis patients with active disease despite optimal treatment with methotrexate, the main objective of this pilot study is to use advance imaging tools such as magnetic resonance imaging and ultrasound to evaluate which treatment option is more efficacious: initiating methotrexate/sulfasalazine combination therapy, or switching to leflunomide monotherapy

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; Ultrasound; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• MRI synovitis score

  four months

Secondary Outcomes (4)

• MRI bone marrow edema score

  4 months

• MRI erosion score

  4 months

• US synovitis score

  4 months

• clinical outcomes

  4 months

Other Outcomes (4)

• US erosion score

  4 months

• US tenosynovitis score

  4 months

• MRI tenosynovitis score

  4 months

Study Arms (2)

Methotrexate plus sulfasalazine

ACTIVE COMPARATOR

ARM 1(Methotrexate(MTX) plus Sulfasalazine(SSZ)) SSZ:Oral form, 2g/day, with escalation regime starting from 1g/day for the first week and increase to 1.5g/day in the next week and increasing to 2g/day by the third week. Total treatment period is 16 weeks. After reaching 2g/day, if patients conditions warrants (and no contraindication), SSZ may be increased at 0.5g per clinic visit) up to a maximum of 3g/day. MTX:Kept at the highest optimal dose.

Drug: Methotrexate plus sulfasalazine

Leflunomide

ACTIVE COMPARATOR

ARM 2:Leflunomide(LEF) LEF: Oral form, 20mg every other day for first 2 weeks then increasing to 20mg per day by the third week. Total treatment period is 16 weeks. Methotrexate:Off

Drug: Leflunomide

Interventions

Methotrexate plus sulfasalazine DRUG

ARM 1(Methotrexate(MTX) plus Sulfasalazine(SSZ)) SSZ:Oral form, 2g/day, with escalation regime starting from 1g/day for the first week and increase to 1.5g/day in the next week and increasing to 2g/day by the third week. Total treatment period is 16 weeks. After reaching 2g/day, if patients conditions warrants (and no contraindication), SSZ may be increased at 0.5g per clinic visit) up to a maximum of 3g/day. MTX:Kept at the highest optimal dose.

Methotrexate plus sulfasalazine

Leflunomide DRUG

ARM 2:Leflunomide(LEF) LEF: Oral form, 20mg every other day for first 2 weeks then increasing to 20mg per day by the third week. Total treatment period is 16 weeks. Methotrexate:Off

Leflunomide

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged between 21 and 65 years.
• Patients with no childbearing potential (For example postmenopausal or sterilised) or have decided not to have offspring(s).
• All female patients must consent not to get pregnant/breastfeed, male patients must consent not to father a child and all must consent to practice effective birth control.
• Fulfills either the 1987 ACR criteria and/or the 2010 ACR / EULAR RA Classification Criteria.
• Seropositivity: Rheumatoid factor (RF) and/or anti -cyclic citrullinated protein antibodies (anti-CCP) must be positive.
• MCPJ(s) and/or Wrist(s) joint(s) involvement.
• Rheumatoid arthritis patients (less than 5 years duration) who remain at least moderately active based on DAS28 score of \> 3.2, following 3 months of therapy with an optimal dose of methotrexate(e.g. at least 15 mg/week).
• If patient is on oral corticosteroids, this should not exceeding 10mg prednisolone daily (or oral steroid equivalent) for at least 4 weeks and should be at an unchanged dose for at least 2 weeks before entering study.
• If patient is on NSAIDs, this should be at an unchanged dose for at least 2 weeks before entering study.
• Glomerular filtration rate \> 60 mls/min/1.73m2.

You may not qualify if:

• Patient known to have the following medical condition(s) will be excluded:
• Other autoimmune disease /inflammatory joint disease/connective tissue disease ( e.g. lupus, seronegative spondylarthropathy (e.g. ankylosing spondylitis/psoriatic arthropathy ), reactive arthritis, overlap syndrome, primary sjogren syndrome and mixed connective tissue disease.)
• Inflammatory arthritis with onset before 18 years old.
• Current or previous history of cancer or lymphoproliferative disease.
• HIV positive status, Hepatitis B/C positive status.
• Persistent and/or severe infection in the previous 12 weeks.
• Major traumatic injury, terminal illness, or other medical condition(s)that could place the patient at risk to participate in the study.
• Clinically relevant cardiovascular (e.g unstable ischemic heart disease), neurological (e.g recent stroke), gastroenterology (e.g active peptic ulcer disease), renal (e.g chronic renal failure), hepatic (e.g alcoholic liver disease, fatty liver) and any other major systemic disease that could i) place the patient at risk to participate in the study; or ii) make protocol implementation difficult; or iii) make study results interpretation difficult.
• Presence of any known condition(s)/circumstance(s) which would negatively impact compliance or study completion.
• Impaired laboratory parameters:
• Hemoglobin less than 10.5 g/dl, white blood count less than 4 x 10 (9)/L , platelet count less than 150 x 10(9)/L.
• Deranged Liver function test: e.g. elevated AST/ALT.
• Wants to consume alcohol while taking the study medications.
• Body weight that is less than 45 kg.
• Pregnancy/Breastfeeding/Male patient wishing to father children.

Sponsors & Collaborators

• Singapore General Hospital: lead

Study Sites (1)

Singapore General Hospital

Singapore, Singapore, 169608, Singapore

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate; Sulfasalazine; Leflunomide

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; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• York Kiat Tan, MBBS,MRCP

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2012
• First Posted: August 7, 2012
• Study Start: July 1, 2012
• Primary Completion: December 1, 2012
• Last Updated: December 2, 2014

Record last verified: 2014-11

Locations

SG (1)