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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Singapore General Hospital
Sponsor:
Information provided by (Responsible Party):
Singapore General Hospital
ClinicalTrials.gov Identifier:
NCT01659242
First received: August 3, 2012
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Methotrexate plus sulfasalazine
Drug: Leflunomide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Leflunomide Versus Sulfasalazine/Methotrexate in Rheumatoid Arthritis Patients With Active Disease Despite Methotrexate: an Ultrasound and Magnetic Resonance Imaging Study

Resource links provided by NLM:


Further study details as provided by Singapore General Hospital:

Primary Outcome Measures:
  • MRI synovitis score [ Time Frame: four months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • MRI bone marrow edema score [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • MRI erosion score [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • US synovitis score [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • clinical outcomes [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Swollen/Tender joint counts, investigator's global assessment of disease activity (0-10), patient's assessment of disease activity (0-10), pain assessment by visual analogue scale (0-10), erythrocyte sedimentation rate, duration (mins) of early morning stiffness, and calculated disease activity indices


Other Outcome Measures:
  • US erosion score [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • US tenosynovitis score [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • MRI tenosynovitis score [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: July 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Methotrexate plus sulfasalazine

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

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.

Other Name: n.a
Active Comparator: Leflunomide

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

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

Other Name: n.a

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Male and female patients aged between 21 and 65 years.
  2. Patients with no childbearing potential (For example postmenopausal or sterilised) or have decided not to have offspring(s).
  3. 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.
  4. Fulfills either the 1987 ACR criteria and/or the 2010 ACR / EULAR RA Classification Criteria.
  5. Seropositivity: Rheumatoid factor (RF) and/or anti -cyclic citrullinated protein antibodies (anti-CCP) must be positive.
  6. MCPJ(s) and/or Wrist(s) joint(s) involvement.
  7. 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).
  8. 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.
  9. If patient is on NSAIDs, this should be at an unchanged dose for at least 2 weeks before entering study.
  10. Glomerular filtration rate > 60 mls/min/1.73m2.

Exclusion Criteria

  1. Patient known to have the following medical condition(s) will be excluded:

    1. 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.)
    2. Inflammatory arthritis with onset before 18 years old.
    3. Current or previous history of cancer or lymphoproliferative disease.
    4. HIV positive status, Hepatitis B/C positive status.
    5. Persistent and/or severe infection in the previous 12 weeks.
    6. Major traumatic injury, terminal illness, or other medical condition(s)that could place the patient at risk to participate in the study.
    7. 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.
    8. Presence of any known condition(s)/circumstance(s) which would negatively impact compliance or study completion.
  2. Impaired laboratory parameters:

    1. 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.
    2. Deranged Liver function test: e.g. elevated AST/ALT.
  3. Wants to consume alcohol while taking the study medications.
  4. Body weight that is less than 45 kg.
  5. Pregnancy/Breastfeeding/Male patient wishing to father children.
  6. Patients with the following medication history will be excluded:

    1. History of Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency.
    2. Known allergy to: i) study medications; or ii) contrast; or iii) drugs whose chemical structures are similar (e.g. sulphonamides, salicylates, etc).
    3. On anticoagulation for any reasons.
    4. Previous treatment (within the last 4 weeks) with: i) oral corticosteroid greater than prednisolone equivalent of 10mg/day; or ii) parenteral/intra-articular corticosteroid injection.
    5. Previous treatment (within the last 12 weeks) with: i) other DMARDs such as sulfasalazine,hydroxychloroquine,chloroquine,gold salts, etc; or ii) investigational drug(s); or iii) other immunosuppressive agents such as cyclophosphamide,cyclosporin,azathioprine and any biologic agents, e.g. anti-TNF.
    6. Previous treatment(any duration) with i) Leflunomide; or ii) Sulfasalazine used together with methotrexate
  7. Contraindication to MRI (e.g. pacemakers, metallic implants/stents, claustrophobia).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01659242

Contacts
Contact: York Kiat Tan, MBBS,MRCP 62223322 tan.york.kiat@sgh.com.sg

Locations
Singapore
Singapore General Hospital Recruiting
Singapore, Singapore, 169608
Contact: York Kiat Tan, MBBS,MRCP    62223322    tan.york.kiat@sgh.com.sg   
Principal Investigator: York Kiat Tan, MBBS,MRCP         
Sponsors and Collaborators
Singapore General Hospital
Investigators
Principal Investigator: York Kiat Tan, MBBS,MRCP Singapore General Hospital
  More Information

No publications provided

Responsible Party: Singapore General Hospital
ClinicalTrials.gov Identifier: NCT01659242     History of Changes
Other Study ID Numbers: YK 01-2012
Study First Received: August 3, 2012
Last Updated: January 2, 2013
Health Authority: Singapore: Health Sciences Authority

Keywords provided by Singapore General Hospital:
Rheumatoid arthritis
Ultrasound
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Leflunomide
Sulfasalazine
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Infective Agents
Anti-Inflammatory Agents, Non-Steroidal

ClinicalTrials.gov processed this record on August 28, 2014