Ignite Creation Date:
2026-03-26 @ 3:18 PM
Ignite Modification Date:
2026-03-31 @ 2:32 PM
Study NCT ID:
NCT07428551
Status:
COMPLETED
Last Update Posted:
2026-02-23
First Post:
2026-02-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Comparative Study of Leflunomide Plus Methotrexate Versus Methotrexate Monotherapy in Refractory Polyarticular Juvenile Idiopathic Arthritis Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001171', 'term': 'Arthritis, Juvenile'}], 'ancestors': [{'id': 'D001168', 'term': 'Arthritis'}, {'id': 'D007592', 'term': 'Joint Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D012216', 'term': 'Rheumatic Diseases'}, {'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077339', 'term': 'Leflunomide'}, {'id': 'D008727', 'term': 'Methotrexate'}], 'ancestors': [{'id': 'D007555', 'term': 'Isoxazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D000630', 'term': 'Aminopterin'}, {'id': 'D011622', 'term': 'Pterins'}, {'id': 'D011621', 'term': 'Pteridines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This is a randomized, open-label, parallel-group controlled trial including 50 children with refractory polyarticular juvenile idiopathic arthritis. Participants were randomized in a 1:1 ratio using random allocation software into an experimental group (leflunomide plus methotrexate) and a control group (methotrexate alone), with 25 patients in each group. The experimental group received oral leflunomide once daily (10-20 mg weight-based) in addition to subcutaneous methotrexate 15 mg/m² weekly. The control group received subcutaneous methotrexate 15 mg/m² weekly. Low-dose corticosteroids were allowed as bridging therapy and tapered gradually. NSAIDs were permitted as needed. Follow-up duration was 24 weeks.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 50}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2024-03-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2026-01-28', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2026-02-19', 'studyFirstSubmitDate': '2026-02-19', 'studyFirstSubmitQcDate': '2026-02-19', 'lastUpdatePostDateStruct': {'date': '2026-02-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in JADAS-27 score from baseline to week 24', 'timeFrame': '24 weeks', 'description': 'The mean change in Juvenile Arthritis Disease Activity Score-27 (range 0-57) from baseline to week 24. Higher scores indicate greater disease activity'}], 'secondaryOutcomes': [{'measure': 'Proportion achieving inactive disease (JADAS ≤1)', 'timeFrame': '24 weeks'}, {'measure': 'Proportion achieving low disease activity', 'timeFrame': '24 weeks'}, {'measure': 'Mean change in JADAS-27 variables', 'timeFrame': '24 weeks'}, {'measure': 'Incidence of adverse events', 'timeFrame': '24 weeks'}, {'measure': 'Change in improvement of functional impairment by CHAQ-B(DI)', 'timeFrame': '24 weeks'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['CHAQ, JADAS-27, LEF, MTX and and Poly articular JIA'], 'conditions': ['Juvenile Idiopathic Arthritis', 'Polyarticular Juvenile Idiopathic Arthritis', 'Refractory Polyarticular Juvenile Idiopathic Arthritis']}, 'referencesModule': {'references': [{'pmid': '36998586', 'type': 'BACKGROUND', 'citation': 'Rezaieyazdi Z, Ravanshad S, Khodashahi M, Bokaeian M, Mehrad Majd H, Salari M. Comparison of the efficacy and safety of methotrexate alone or in combination with leflunomide in the treatment of juvenile idiopathic arthritis: a double-blind, placebo-controlled, randomized trial. Reumatologia. 2023;61(1):4-12. doi: 10.5114/reum/161317. Epub 2023 Mar 8.'}, {'pmid': '31021516', 'type': 'BACKGROUND', 'citation': 'Ringold S, Angeles-Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, Colbert RA, Feldman BM, Ferguson PJ, Gewanter H, Guzman J, Horonjeff J, Nigrovic PA, Ombrello MJ, Passo MH, Stoll ML, Rabinovich CE, Schneider R, Halyabar O, Hays K, Shah AA, Sullivan N, Szymanski AM, Turgunbaev M, Turner A, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res (Hoboken). 2019 Jun;71(6):717-734. doi: 10.1002/acr.23870. Epub 2019 Apr 25.'}]}, 'descriptionModule': {'briefSummary': "A randomized control trial open level and parallel design was conducted in the department of paediatrics, Bangladesh Medical University (BMU). All diagnosed cases of Refractory Polyarticular JIA according to ILAR criteria, unresponsive to MTX were enrolled in this study. After getting written informed consent from the parents/legal guardians, a detailed structured data collection sheet was used for data collection. After enrollment all participants were allocated into experimental group and control group by randomization using random allocation software version 2.0. Total sample size of this study is 50 and 25 participants in each group. All patients of experimental group were given leflunomide along with existing MTX in refractory polyarticular JIA patients and injectable MTX were given at standard dose(15mg/m² BSA) Considering high disease activity steroid were continued in both group at low bridging dose 0.05-1 mg/kg/dose. Patient's disease activity status was assessed by JADAS-27 at initial visit, 6th weeks, 12 weeks and 24 weeks. Functional impairment was assessed by CHAQ-B (DI) at baseline and 24th weeks of treatment. Statistical analysis of the collected data were carried out by using an appropriate statistical tool.", 'detailedDescription': 'Study design:\n\nRandomized control trial, Open level, Parallel design\n\nPlace of study:\n\nDepartment of Pediatric Rheumatology Division (OPD clinic and Inpatient), Department of Paediatrics, Bangladesh Medical University\n\nStudy period:\n\nFrom March, 2024 to January, 2026.\n\nStudy Population:\n\nAll diagnosed cases of Refractory Polyarticular Juvenile Idiopathic Arthritis (JIA) according to ILAR, 2001 unresponsive to methotrexate (at standard dose of 15mg/m² body surface area at least 3-6 months) as monotherapy or together with low dose steroid as bridge therapy who attended Paediatric Rheumatology Division (OPD clinic and inpatient), Department of Paediatrics of BMU, during the study period were the study population.\n\nSampling method:\n\nPurposive sampling was done.\n\nSample size: 50\n\nInclusion criteria:\n\nAll diagnosed cases of Refractory Polyarticular Juvenile Idiopathic Arthritis (JIA) according to ILAR, 2001 unresponsive to methotrexate (at standard dose of 15mg/m² body surface area at least 3-6 months) as monotherapy or together with low dose steroid as bridge therapy who attended Paediatric Rheumatology Division (OPD clinic and inpatient), Department of Paediatrics of BMU, during the study period.\n\nExclusion criteria:\n\n1. A patient with prior or current infectious disorders, including active/latent tuberculosis, and/or H/O chronic or recurrent severe infections, including opportunistic infections.\n2. A patient with leucopenia (White blood cell count \\< 3000/mm3), neutropenia (Neutrophil count \\< 1000/mm3) and thrombocytopenia (Platelet count \\< 100000/mm3).\n3. Serum creatinine \\> upper limit of normal reference range.\n4. Alanine aminotransaminase (ALT) more than 2 times of upper normal limit.\n5. All diagnosed cases of refractory polyarticular JIA who did not give the consent during the study period.\n\nStudy variables:\n\nClinical characteristic variables\n\n* Age\n* Gender\n* Age at disease onset\n* Age group\n* Disease duration\n* Physician global assessment 0-10cm VAS\n* Parent/ patient global assessment 0-10 cm VAS\n* Active joint count (0-27 joints)\n\nLaboratory variables:\n\n* CBC with ESR\n* S.ALT\n* S. creatinine\n* Urine RME\n\nOutcome variables:\n\nFor Efficacy:\n\n1. Improvement according to JADAS-27 criteria\n2. Functional improvment by CHAQ-B (DI)\n\nFor Safety:\n\n1. Any infection and allergies\n2. Raised liver enzyme\n3. Hematological abnormalities (Hb, Total count, Differentials, Platelet count).\n4. Raised S. Creatinine.\n\nStudy Procedure:\n\nIn this randomized control trial 50 diagnosed cases of refractory polyarticular JIA fulfilling inclusion criteria according to ILAR, 2001 were evaluated. The children with acute infections, chronic kidney disease, chronic liver disease, and any lymphoproliferative disorders and children or parents who were unwilling to give their consent were exluded from study.\n\nAfter having approval by the Institutional Review Board(IRB), BMU, documented informed consent were taken from all patients or parents or care-givers and assent were taken from participants above 7 years of old after informal assessment in clinic.\n\nA predesigned questionnaire was filled out for all patients completed for each patient by interviewing them from their parents and also from their medical records. At BMU, each outpatient and inpatient is assigned a Paediatric Rheumatology and Immunology Clinic (PRIC) number and provided with a record book in which clinical complaints, examination findings, investigation results, disease status, treatment details, and follow-up plans are systematically documented at every visit. The same information is simultaneously entered into a web-based database (paedrhum.com) for secure electronic storage.\n\nFollowing enrollment in the study, patients were allocated by simple randomization using random allocation software version 2.0 into experimental group and control group. 25 patients were taken in each group. Comprehensive medical history were taken including age at presentation, age at diagnosis, initial clinical presentation, use of sterod, NSAID and DMARDs. A full physical examination will be performed including tender joints, swollen joints, limitation of movement in joints, lymphadenopathy, skin rash, hepatomegaly and/or splenomegaly and serositis will be assessed. Baseline investigations were done including Hb%, total leukocyte count (TLC), differential count (DC), platelet count (PLT), ESR, serum ALT, serum creatinine, Rheumatoid factor, antinuclear antibody, chest X-ray, routine and microscopic examination of urine.\n\nDisease activity were evaluated using a standardized questionnaire containing JADAS-27 (Juvenile Arthritis Disease Activity score in 27 joints) - ankles, knees, hips, meta- carpophalangeal joints (from first to third), proximal interphalangeal joints, wrists, elbows and cervical spine which include number of joint with active disease (swollen joints, tender joints and restriction of movement), physician and patient global assessment of disease activity and acute phase reactant (ESR).\n\nGlobal assessment of disease activity by physician and patient/parent were done by using visual analog scale (VAS). A 0- 10 cm horizontal line were taken to represent the status of global assessment of disease activity. The line begins at zero indicating disease activity absent and the extreme ends of the line is 10 cm which indicates the activity of disease is maximum (100%). From the initial visit to follow up visit VAS were assessed by the investigator and opinion were taken from the rheumatology team. When a patient marked the line at 7 cm point of the VAS, it was assessed as 70% of disease activity, subsequently 5 cm and 3 cm were indicated 50% and 30% of disease activity.\n\nESR which was converted to a scale from 0 to 10 by following formula - {ESR (mm in 1st hour) - 20}/10\n\n\\*\\*ESR with values \\< 20 mm in 1st hour were converted to 0 and values \\>120 mm in 1st hour were converted to 10.\n\nA global score of 0 to 57 was obtained by calculating the JADAS-27 as the arithmetic sum of the scores of its four components. A JADAS-27 score of higher than 8.5 is indicative of high disease activity, whereas a score of 3.9 to 8.5 indicates moderate disease activity, 1.1 to 3.8 indicates low disease activity and ≤1 indicates no disease activity.\n\nFunctional assessment was done by CHAQ-B (DI) which has eight functional domains: dressing and personal care, rising from a seated position, eating, walking, personal hygiene, reaching, gripping, and daily activities. Each domain consists of several items scored on a 4-point scale ranging from 0 (no difficulty) to 3 (unable to perform). For scoring, the highest item score within each domain was used, and the average of these scores generated the Disability Index, which represented the overall degree of functional impairment.\n\nAll patients of experimental group were given leflunomide along with existing methotrexate. Leflunomide will be prescribed as once daily oral dose before meal on weight based 10mg for patients 10 to \\<20kg, 15mg for patients 20-40kg and 20mg for patients \\>40kg (Rabinovich, 2024, p. 1466). Every medication were purchased from a single pharmaceutical company. Along with leflunomide, all the study participants of this group received MTX subcutaneously at a dose of 15 mg/m2/ week in a single weekly dose. Participants of control group were given existing MTX subcutaneously at a dose of 15 mg/m²/ week in a single weekly dose at night. Considering high disease activity level, steroids were continued at low bridging dose at 0.5-1mg/kg/day and then it was stopped by gradually tapering in both group. Nonsteroidal anti-inflammatory drugs were continued as necessary (Chickermane and Khubchandani, 2013).\n\nAll the participants received calcium and vitamin D combination along with folic/folinic acid routinely at the dose of 1000 mg calcium and 400 vitamin D daily and folic/folinic acid 5 mg once weekly. No other conventional or biological DMARDS were used in both group and no other DMARDs except methotrexate will not also be given before leflunomide.\n\nBlood was drawn from the patients by venipuncture for the following baseline laboratory tests: Complete Blood Count (CBC) with ESR, Serum ALT, Serum Creatinine, Rheumatoid factor, antinuclear antibody, CXR, Mantoux test, HBsAg, routine and microscopic examination of urine were done.\n\nAll lab tests were completed from BMU. CBC with ESR and routine and microscopic examination of urine were done from Clinical pathology Department. S.ALT, S.Creatinine were done in the Department of Biochemistry and HBsAg was performed in the Department of Virology, BMU. X-ray chest was performed in the Department of Radiology and Imaging, BMU.\n\nAll the patients were followed up initially at 6th, 12th and then at 24th weeks to assess clinical and laboratory status of disease activity and to identify any adverse effects.\n\nAlong with clinical follow up, investigations including Hb%, TLC, DC , PLT, ESR , serum ALT, serum creatinine, urine R/E were done at scheduled follow up. According to JADAS-27 criteria baseline measurements were compared with those obtained at the 6th weeks, 12th weeks and 24th weeks follow up.\n\nContinuous communication were maintained with study subjects by cell phone to ensure drug adherence and follow-up visits. Patients who developed serious medication-associated adverse reactions like organ involvement or patients requiring hospital admission were discontinued from therapy.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '15 Years', 'minimumAge': '1 Day', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria: -\n\nAll diagnosed cases of Refractory Polyarticular Juvenile Idiopathic Arthritis (JIA) according to ILAR, 2001 unresponsive to methotrexate (at standard dose of 15mg/m² body surface area at least 3-6 months) as monotherapy or together with low dose steroid as bridge therapy who attended Paediatric Rheumatology Division (OPD clinic and inpatient), Department of Paediatrics of BMU, during the study period.\n\nExclusion Criteria:\n\n* 1\\. A patient with prior or current infectious disorders, including active/latent tuberculosis, and/or H/O chronic or recurrent severe infections, including opportunistic infections.\n\n 2\\. A patient with leucopenia (White blood cell count \\< 3000/mm3), neutropenia (Neutrophil count \\< 1000/mm3) and thrombocytopenia (Platelet count \\< 100000/mm3).\n\n 3\\. Serum creatinine \\> upper limit of normal reference range. 4. Alanine aminotransaminase (ALT) more than 2 times of upper normal limit. 5. All diagnosed cases of refractory polyarticular JIA who did not give the consent during the study period.'}, 'identificationModule': {'nctId': 'NCT07428551', 'acronym': 'JIA', 'briefTitle': 'Comparative Study of Leflunomide Plus Methotrexate Versus Methotrexate Monotherapy in Refractory Polyarticular Juvenile Idiopathic Arthritis Patients', 'organization': {'class': 'OTHER', 'fullName': 'Bangladesh Medical University'}, 'officialTitle': 'Comparative Study of Leflunomide Plus Methotrexate Versus Methotrexate Monotherapy in Refractory Polyarticular Juvenile Idiopathic Arthritis Patients', 'orgStudyIdInfo': {'id': 'BSMMU/2024/2965'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Leflunomide plus Methotrexate (Experimental group)', 'description': 'Experimental group', 'interventionNames': ['Drug: Leflunomide plus Methotrexate']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Methotrexate Monotherapy (Control Group)', 'description': 'Control group', 'interventionNames': ['Drug: Methotrexate Monotherapy']}], 'interventions': [{'name': 'Leflunomide plus Methotrexate', 'type': 'DRUG', 'description': 'In experimental group, all patients were given leflunomide along with existing methotrexate. Leflunomide was prescribed as once daily oral dose before meal on weight based 10mg for patients 10 to \\<20kg, 15mg for patients 20-40kg and 20mg for patients \\>40kg. Every medication were purchased from a single pharmaceutical company. Along with leflunomide, all the study participants of this group were received existing MTX subcutaneously at a dose of 15 mg/m2/ week in a single weekly dose. Considering high disease activity level, steroids were continued at low bridging dose at 0.5-1mg/kg/day and then it was stopped by gradually tapering in both group. Nonsteroidal anti-inflammatory drugs were continued as necessary', 'armGroupLabels': ['Leflunomide plus Methotrexate (Experimental group)']}, {'name': 'Methotrexate Monotherapy', 'type': 'DRUG', 'description': 'Participants of control group were given existing MTX subcutaneously at a dose of 15 mg/m²/ week in a single weekly dose at night. Considering high disease activity level, steroids were continued at low bridging dose at 0.5-1mg/kg/day and then it was stopped by gradually tapering in both group. Nonsteroidal anti-inflammatory drugs were continued as necessary.', 'armGroupLabels': ['Methotrexate Monotherapy (Control Group)']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Dhaka', 'country': 'Bangladesh', 'facility': 'Bangladesh Medical University', 'geoPoint': {'lat': 23.7104, 'lon': 90.40744}}], 'overallOfficials': [{'name': 'Md. Mahbubur Rahman', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Phase B Resident'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Bangladesh Medical University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Dr. Md. Mahbubur Rahman', 'investigatorFullName': 'Md Mahbubur Rahman', 'investigatorAffiliation': 'Bangladesh Medical University'}}}}