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Trial record 71 of 117 for:    "Connective Tissue Disease" | "Methylprednisolone"

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

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ClinicalTrials.gov Identifier: NCT02930343
Recruitment Status : Recruiting
First Posted : October 12, 2016
Last Update Posted : February 28, 2018
Sponsor:
Information provided by (Responsible Party):
Dr. Vir Singh Negi, Jawaharlal Institute of Postgraduate Medical Education & Research

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)

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Methotrexate Drug: Leflunomide Drug: Hydroxychloroquine Drug: Prednisolone Drug: Folic Acid Drug: Sulfasalazine Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : September 2016
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: group 1- MTX+LEF+HCQ
Active 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.
Drug: Methotrexate
Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic diseases
Other Name: folitrax, MTX

Drug: 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
Other Name: Arava, Lefno, LEF

Drug: 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.
Other Name: HCQ

Drug: 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)
Other Name: Steroids, Glucocorticoids

Drug: Folic Acid
Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.
Other Name: Folvite

Active Comparator: group 2- MTX+SSZ+HCQ
Combination 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.
Drug: Methotrexate
Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic diseases
Other Name: folitrax, MTX

Drug: 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.
Other Name: HCQ

Drug: 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)
Other Name: Steroids, Glucocorticoids

Drug: Folic Acid
Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.
Other Name: Folvite

Drug: 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)
Other Name: Saaz, SSZ




Primary Outcome Measures :
  1. 1.Good response according to European league against rheumatism (EULAR) response [ Time Frame: 3 months ]

    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


Secondary Outcome Measures :
  1. Disease activity as per Ultrasound-7 (US-7) score [ Time Frame: 3 months ]
    The US7 score is sensitive to change in a large cohort of patients with rheumatoid arthritis over 12 months of therapy Tina M Backhaus et al, 2012

  2. radiographic damage by SENS scoring system [ Time Frame: 3 months ]
    The Simple Erosion Narrowing Score (SENS) method, derived from the Sharp/van der Heijde method as an easier, quicker and quite reliable to score joint lesions, especially in the first few years of disease (van der Heijde D, Dankert T, Nieman F, Rau R, Boers M. Reliability and sensitivity to change of a simplification of the Sharp/van der Heijde radiological assessment in rheumatoid arthritis. Rheumatology (Oxford) 1999

  3. Adverse drug reactions [ Time Frame: 3 months ]
    Infections, transaminitis, nausea, vomiting, derranged renal function tests etc

  4. Indian health assessment questionnaire (iHAQ) [ Time Frame: 3 months ]
    Indian version of HAQ (iHAQ) has been validated in patients with RA, which comprises 12 questions (nine basic and three advanced activity of daily living) relevant to the Indian population. For each question there is a four-level difficulty scale ranging from 0 to 3 that represent no difficulty ('0'), some difficulty ('1'), much difficulty ('2'), and inability to do ('3'). The final score is the mean of the highest scores across the eight categories and ranges from 0 to 3, with higher levels indicating more disability



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02930343


Contacts
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Contact: Vir S Negi, DM 04132297358 vsnegi22@yahoo.co.in
Contact: Pooja Belani, MD 8940482248 drpoojabelani@gmail.com

Locations
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India
Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research Recruiting
Pondicherry, India, 605006
Contact: Dr. Vir Singh Negi, DM    0413-2297358    vsnegi22@yahoo.co.in   
Contact: Dr. Pooja Belani, MD    8940482248    drpoojabelani@gmail.com   
Sponsors and Collaborators
Jawaharlal Institute of Postgraduate Medical Education & Research
Investigators
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Principal Investigator: Vir S Negi, DM Jawaharlal Institute of Postgraduate Medical Education & Research
Study Chair: Pooja Belani, MD Jawaharlal Institute of Postgraduate Medical Education & Research

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Responsible Party: Dr. Vir Singh Negi, Professor and head of the department, Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education & Research
ClinicalTrials.gov Identifier: NCT02930343     History of Changes
Other Study ID Numbers: JIP/IEC/2016/27/893
First Posted: October 12, 2016    Key Record Dates
Last Update Posted: February 28, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Connective Tissue Diseases
Prednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone Acetate
Methylprednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Hydroxychloroquine
Leflunomide
Sulfasalazine
Antirheumatic Agents
Glucocorticoids
Folic Acid
Vitamin B Complex
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action