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Trial record 39 of 117 for:    "Connective Tissue Disease" | "Methylprednisolone"

Treatment With Leflunomide in Patients With Polymyalgia Rheumatica (PMRLEFRCT)

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ClinicalTrials.gov Identifier: NCT03576794
Recruitment Status : Recruiting
First Posted : July 3, 2018
Last Update Posted : June 3, 2019
Sponsor:
Collaborator:
Dutch Arthritis Foundation Reuma Nederland
Information provided by (Responsible Party):
Elisabeth Brouwer, University Medical Center Groningen

Brief Summary:

Over the last decades outcome has greatly improved for rheumatoid arthritis (RA) and spondyloarthritis (SpA). This is in sharp contrast to the situation for polymyalgia rheumatica (PMR), with a lifetime prevalence of 2.4% for women and 1.7% for men, PMR is the commonest auto-inflammatory musculoskeletal disease in adults aged ≥50 years. Due to population ageing, the number of PMR patients will likely double in the decades to come (CBS). Glucocorticoids (GC) are the mainstay of treatment. However, there is an unmet medical need of alternatives in the treatment of PMR as 50% of patients will relapse or have difficulties to reduce the corticosteroid doses. Also, there is increasing awareness of steroid related toxicity and in addition, long-term toxicity is a well-known side-effect of glucocorticoids in PMR.

Low dose methotrexate (< 10 mg per week) has been tested in two blinded randomized control trials and 4 open label studies and has shown low to moderate efficacy as corticosteroid-sparing agent. Studies on tumor necrosis factor (TNF) blockers yielded negative results. The effectiveness of leflunomide has only been convincingly demonstrated in case series.

The high rate of relapses and adverse events in steroid treated patients indicate that alternative adjuvant agents are needed.

There is evidence that leflunomide could serve as steroid sparing agent and that leflunomide can be used to prevent relapses in the clinical management of polymyalgia rheumatica.

We will perform a randomized placebo controlled trial. Eligible patients will be randomly assigned in a 1:1 ratio receiving either leflunomide 20 mg once daily + glucocorticoids , or placebo + glucocorticoids.


Condition or disease Intervention/treatment Phase
Polymyalgia Rheumatica Drug: Leflunomide 20 mg Drug: Prednisolone Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 94 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, randomized, double-blind, placebo controlled treatment study during 12 months (part I) and an additional open-label follow-up of 12 months (part II).
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: A Multicenter Randomized Placebo Controlled Treatment Study of Leflunomide in Polymyalgia Rheumatica
Actual Study Start Date : March 1, 2019
Estimated Primary Completion Date : November 1, 2022
Estimated Study Completion Date : November 1, 2022


Arm Intervention/treatment
Active Comparator: Leflunomide treatment
Patients will receive prednisolone 15 mg once daily and will be randomized within 4 weeks of the start of glucocorticoid therapy (prednisolone). Prednisolon will be tapered according to a short fixed protocol with a slow gradual taper till 0 in week 27. During the first 2 weeks after randomization patients will receive Leflunomide 20 mg every other day in order to prevent early drug withdrawal due to side effects. After 2 weeks Leflunomide will be increased to 20 mg once daily and this therapy will be continued during 12 months.
Drug: Leflunomide 20 mg
During the first 2 weeks after randomization patients will receive Leflunomide 20 mg every other day. After 2 weeks Leflunomide will be increased to 20 mg once daily and this therapy will be continued during 12 months.

Drug: Prednisolone
Patients in both groups will receive prednisolone 15 mg once daily and will be randomized within 4 weeks of the start of glucocorticoid therapy (prednisolone). Prednisolon will be tapered according to a short fixed protocol with a slow gradual taper till 0 in week 27.

Placebo Comparator: Placebo control
Patients will receive prednisolone 15 mg once daily and will be randomized within 4 weeks of the start of glucocorticoid therapy (prednisolone). Prednisolon will be tapered according to a short fixed protocol with a slow gradual taper till 0 in week 27. During the first 2 weeks after randomization patients will receive placebo 20 mg every other day in order to prevent early drug withdrawal due to side effects. After 2 weeks placebo will be increased to 20 mg once daily and this therapy will be continued during 12 months.
Drug: Prednisolone
Patients in both groups will receive prednisolone 15 mg once daily and will be randomized within 4 weeks of the start of glucocorticoid therapy (prednisolone). Prednisolon will be tapered according to a short fixed protocol with a slow gradual taper till 0 in week 27.




Primary Outcome Measures :
  1. PMR relapse [ Time Frame: Within first 12 months of the study participation ]

    Relapse or recurrence will be measured according to an adaptation, based on expert opinion, to consensus criteria for PMR:

    • Patient global higher than 3/10 and
    • Physician global higher than 1/10 and
    • An increased CRP ( > 5 mg/L)

    It is called a "relapse" if it was observed during glucocorticoid tapering and is called a "recurrence" if it was observed after glucocorticoid withdrawal.



Secondary Outcome Measures :
  1. Time till first relapse within first 24 months [ Time Frame: Within first 24 months of the study participation ]
    Time measured in days

  2. Percentage of patients with at least 1 relapse in the first 12 or 24 months [ Time Frame: Within first 24 months of the study participation ]
    Percentage: patients with relapse in the first 12 or 24 months divided by total participating patients.

  3. Number of relapsing patients within the first 24 months. [ Time Frame: Within first 24 months of the study participation ]
  4. Time till glucocorticoid free remission [ Time Frame: Within first 24 months of the study participation ]
    Total days until patient has no glucocorticoid treatment and no signs of PMR.

  5. Glucocorticoid-sparing effect [ Time Frame: Within first 24 months of the study participation ]
    1. Glucocorticoid dose after 6, 12, 18 and 24 months.
    2. Cumulative glucocorticoid dose after 12, 18 and 24 months

  6. Number of participants with adverse events and serious adverse events as assessed by MedDRA V21.0 [ Time Frame: Within first 24 months of the study participation ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written informed consent
  2. Female or male aged ≥ 50 years
  3. PMR according to the American College of Rheumatology (ACR)/European league Against Rheumatism (EULAR) 2012 PMR core (essential) classification criteria
  4. Newly diagnosed PMR being on glucocorticoids for less than 4 weeks

Exclusion Criteria:

  1. Presence of any other connective tissue disease, including vasculitis/giant-cell arteritis
  2. PMR on glucocorticoids for >4 week or >25 mg/day
  3. History of alcohol or drug abuse or current alcohol or drug abuse
  4. Transplanted organ (except corneal transplant performed more than 3 months prior to screening)
  5. Evidence (as assessed by the investigator) of active infection, presence of hepatitis B surface antigen or hepatitis C antibody in blood, HIV positivity.
  6. Malignancy within 5 years prior to screening, except for non-melanoma skin cancer
  7. Exposure to DMARD/biological in the last 5 years
  8. Pain syndromes, e.g. fibromyalgia, drug-induced myalgia
  9. Active thyroid disease
  10. Neurological diseases, e.g. Parkinson's disease
  11. Contraindications for Leflunomide (serious immunodeficiency, e.g. AIDS, cytopenia as defined under 12, moderate to severe kidney failure (as defined under 12), liver test abnormality (as defined under 12)
  12. Laboratory abnormalities:

    • Glomerular filtration rate <50 ml/min
    • Alanine-aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5x upper limit of normal
    • Platelet count <100 x 109/L (100,000/mm3)
    • Hemoglobin <85 g/L (8.5 g/dL; 5.3 mmol/L)
    • White blood cells <3.0 x 109/L (3,000/mm3)Absolute neutrophil count <2.0 x 109/L (2,000/mm3)
    • Absolute lymphocyte count <0.5 x 109/L (500/mm3)
  13. Uncontrolled or poorly controlled hypertension
  14. Major surgery or hospitalization within 3 month prior to screening
  15. Any medical condition that could interfere with the implementation or interpretation of the study or with the safety of the patient during the study.

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): NCT03576794


Contacts
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Contact: Elisabeth Brouwer +3150 3613432 e.brouwer@umcg.nl
Contact: Maria Sandovici +3150 3613432 m.sandovici01@umcg.nl

Locations
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Netherlands
ZGT Almelo Recruiting
Almelo, Netherlands, 7609 PP
Contact: Edgar Colin, MDPhD         
Contact: Celina Alves, MDPhD         
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Contact: Elisabeth Brouwer, dr    +3150 3613432    e.brouwer@umcg.nl   
Contact: Maria Sandovici, dr    +3150 3613432    m.sandovici01@umcg.nl   
Sponsors and Collaborators
Elisabeth Brouwer
Dutch Arthritis Foundation Reuma Nederland
Investigators
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Principal Investigator: Elisabeth Brouwer University Medical Center Groningen
Principal Investigator: E.M. Colin ZGT Almelo

Publications:
Dejaco C, Singh YP, Perel P, Hutchings A, Camellino D, Mackie S, Abril A, Bachta A, Balint P, Barraclough K, Bianconi L, Buttgereit F, Carsons S, Ching D, Cid M, Cimmino M, Diamantopoulos A, Docken W, Duftner C, Fashanu B, Gilbert K, Hildreth P, Hollywood J, Jayne D, Lima M, Maharaj A, Mallen C, Martinez-Taboada V, Maz M, Merry S, Miller J, Mori S, Neill L, Nordborg E, Nott J, Padbury H, Pease C, Salvarani C, Schirmer M, Schmidt W, Spiera R, Tronnier D, Wagner A, Whitlock M, Matteson EL, Dasgupta B; European League Against Rheumatism; American College of Rheumatology. 2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheumatol. 2015 Oct;67(10):2569-80. doi: 10.1002/art.39333.

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Responsible Party: Elisabeth Brouwer, Principal investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT03576794     History of Changes
Other Study ID Numbers: ABR57022
First Posted: July 3, 2018    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Manuscript after publication
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Within 2 years after study termination, study data will be available and published
Access Criteria: Study data will be available upon request to the principal investigator

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Elisabeth Brouwer, University Medical Center Groningen:
PMR RCT
Leflunomide

Additional relevant MeSH terms:
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Connective Tissue Diseases
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Polymyalgia Rheumatica
Giant Cell Arteritis
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Arteritis
Vasculitis
Skin Diseases, Vascular
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Glucocorticoids
Leflunomide
Anti-Inflammatory Agents