|- candidate number||29946|
|- NTR Number||NTR7632|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||23-nov-2018|
|- Secondary IDs||NL-nummer: NL66544.091.18 CMO Arnhem-Nijmegen|
|- Public Title||Methotrexate and leflunomide combination therapy in psoriatic arthritis |
|- Scientific Title||Comparing Methotrexate monotherapy with methotrexate Plus LEflunomide combination ThErapy in Psoriatic Arthritis: A pragmatic
randomized placebo-controlled double-blind clinical trial|
|- Healt Condition(s) or Problem(s) studied||Psoriatic arthritis, Psoriatic arthritis, Methotrexate , Leflunomide|
|- Inclusion criteria||-Adult male or female|
-Age ≥16 years
-Clinical diagnoses of Psoriatic arthritis
-Evidence of active disease defined as ≥2 swollen joints, dactylitis counts as 1 swollen joint
-Subjects that have used cDMARDs and/or bDMARDs before, must have discontinued this treatment for at least 6 months prior to baseline visit
-Subjects who are already taking NSAIDs/COX-2 inhibitors may participate in the study but the dose has to be stable for at least one week prior to first dose of study drug
-Oral or injected corticosteroids (intramuscular, intravenous and intra-articular) have to be discontinued 8 weeks prior to first dose of study drug
-If fumaric acid is used at baseline, this will be discontinued and switched to study medication (according to usual care)
|- Exclusion criteria||-Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 2 years after the last dose of study drug or up to 11 days after treatment when washout procedure is executed.|
-Male subject who is considering fathering a child or donating sperm during the study or for approximately 2 years after the last dose of study drug or up to 11 days after treatment when washout procedure is executed.
-History of an inadequate response to MTX or LEF (prescribed by a rheumatologist for joint disease).
-Current severe infection including, but not limited to:
o Active human immunodeficiency virus (HIV)
o Active TB
-History of an allergic reaction or significant sensitivity to constituents of the study drugs
-Current or history of hepatic disease, including, but not limited to:
o Non-alcoholic Fatty Liver Disease (NAFLD)
o Non-alcoholic Steatohepatitis (NASH)
o Alcoholic cirrhosis
-History of clinically significant (per Investigator's judgment) drug or alcohol abuse within the last 6 months prior to baseline visit.
-Current or recent history of a severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular or neurologic disease.
-History of any fibromyalgia or diagnosis of inflammatory rheumatic disease other than PsA. Prior history of fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis of fibromyalgia was made incorrectly.
-Abnormal laboratory values within 1 month prior to baseline visit:
o Serum alanine transaminase (ALT) > 1.5 × ULN;
o Estimated glomerular filtration rate (GFR) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73m2;
o Total white blood cell count (WBC) < 3,000/μL;
o Platelet count < 100,000/μL;
o Hemoglobin < 10 g/dL (6.3 mmol/L).
-Current persistent hypertension requiring start or change of treatment regimen
-Malignancy in the past 5 years except for non-melanoma skin cancer
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2019|
|- planned closingdate||1-nov-2021|
|- Target number of participants||78|
|- Interventions||Patients will be randomised 1:1 into two groups.|
Arm 1: methotrexate monotherapy (methotrexate 25 mg once weekly plus 2 placebo tablets daily) Arm 2: methotrexate and leflunomide combination therapy (methotrexate 25 mg once weekly plus 2 leflunomide 10 mg tablets daily)
|- Primary outcome||Primary endpoint is the difference in efficacy between monotherapy MTX and combination therapy MTX plus LEF on the Psoriatic Arthritis Disease Activity Score (PASDAS) at 16 weeks. |
|- Secondary outcome||Key secondary parameters are: change in skin score, enthesitis score, dactylitis score and swollen/tender joint count. Furthermore, the difference in immunoprofile, treatment failure, and the percentage of (S)AE’s between the two groups will be assessed. |
|- Timepoints||- Baseline|
- 8 weeks
- 16 weeks
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES|| Michelle Mulder|
|- CONTACT for SCIENTIFIC QUERIES|| Michelle Mulder|
|- Sponsor/Initiator ||Sint Maartenskliniek Nijmegen|
(Source(s) of Monetary or Material Support)
|Local research fund|
|- Brief summary||Rationale: |
Psoriatic arthritis (PsA) is a heterogeneous disease which involves at least five domains: peripheral joint disease, enthesitis, dactylitis, axial involvement, and skin and nail psoriasis. Once diagnosed PsA is notoriously difficult to treat. Monotherapy with first-line anti-rheumatic drugs (conventional (c)DMARDs: e.g. methotrexate, leflunomide) appears to lack efficacy in a substantial portion of patients. The effectiveness of cDMARDs on multiple domains in PsA is either inconsistent or not known. Furthermore, the effectiveness of combination cDMARD therapy in PsA has not been researched in representative studies. A combination of Methotrexate (MTX) and Leflunomide (LEF) has been proven effective in patients with rheumatoid arthritis. Therefore, we hypothesize that MTX and LEF combination therapy is superior to MTX monotherapy in patients with psoriatic arthritis.
To compare the effectiveness of MTX monotherapy with MTX and LEF combination therapy in cDMARD-naïve psoriatic arthritis patients.
Monocentre, pragmatic, double-blind, placebo-controlled, randomized clinical trial in cDMARD-naïve psoriatic arthritis patients. Patients will be randomised 1:1 to receive either MTX monotherapy (arm 1) or MTX and LEF combination therapy (arm 2). Treatment response will be assessed at 16 weeks and in case of treatment failure, further treatment decisions are based on shared decision making between patient and treating physician and according to local treatment protocol (usual care).
A total of 78 cDMARD-naïve psoriatic arthritis patients, aged ≥16 years.
One group receives methotrexate 25 mg (oral or subcutaneous) once weekly plus 2 placebo tablets daily. The other group receives methotrexate 25 mg (oral or subcutaneous) once weekly plus 2 leflunomide 10 mg tablets daily.
Main study parameters/endpoints:
Primary endpoint is the difference in efficacy between monotherapy MTX and combination therapy MTX plus LEF on the Psoriatic Arthritis Disease Activity Score (PASDAS) at 16 weeks.
Key secondary parameters are: change in skin score, enthesitis score, dactylitis score and swollen/tender joint count. Furthermore, the difference in immunoprofile, treatment failure, and the percentage of (S)AE’s between the two groups will be assessed.
|- Main changes (audit trail)|
|- RECORD||23-nov-2018 - 10-dec-2018|