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AzTrials

Rheumatoid ArthritisPhase 3NCT02930343

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

A Phase 3 study testing Methotrexate, Leflunomide and Hydroxychloroquine in people with Rheumatoid Arthritis, run by Jawaharlal Institute of Postgraduate Medical Education & Research at 1 site in India.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Methotrexate, Leflunomide and Hydroxychloroquine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
136 participants
Where
1 siteIndia
Study dates
Sep 2016to Aug 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

India1 site

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

    Puducherry, 605006

Other trials in India

About this study

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

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)

Read the 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.

Being tested
Methotrexate, Leflunomide, Hydroxychloroquine, Prednisolone, Folic Acid
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethotrexateDrug

    Also called folitrax, MTX

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

  • LeflunomideDrug

    Also called Arava, Lefno, LEF

    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

  • HydroxychloroquineDrug

    Also called HCQ

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

  • PrednisoloneDrug

    Also called Steroids, Glucocorticoids

    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 AcidDrug

    Also called Folvite

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

  • SulfasalazineDrug

    Also called Saaz, SSZ

    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)

Study groups in NCT02930343
Study groupRoleWhat they receive
group 1- MTX+LEF+HCQActive comparatorActive 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.
Receives: Drug: Methotrexate; Drug: Leflunomide; Drug: Hydroxychloroquine; Drug: Prednisolone; Drug: Folic Acid
group 2- MTX+SSZ+HCQActive comparatorCombination 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.
Receives: Drug: Methotrexate; Drug: Hydroxychloroquine; Drug: Prednisolone; Drug: Folic Acid; Drug: Sulfasalazine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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-

    1. Tender joint count 28
    2. Swollen joint count 28
    3. ESR
    4. Patient global assessment of health

    Measured: 12 weeks

Secondary outcomes (3)

  1. 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

    Measured: 12 weeks

  2. Number of Participants With Adverse Drug Reactions

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

    Measured: 24 weeks

  3. 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

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2016 (estimated)
  2. Study startSep 2016
  3. Primary completionAug 2018
  4. Study completionAug 2018

Why it stopped: Due to time constraints, the study was halted prematurely

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
136 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02930343
Sponsor's protocol ID
JIP/IEC/2016/27/893
Status last verified
Jul 2021
First submitted
13 Sep 2016
Last updated
27 Jul 2021
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34586472

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Methotrexate, Leflunomide and Hydroxychloroquine in people with Rheumatoid Arthritis, run by Jawaharlal Institute of Postgraduate Medical Education & Research at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Achieving Good EULAR Response at the End of 12 Weeks (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02930343, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2021.

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