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Methotrexate and Mycophenolate Mofetil for UVEITIS (FAST)

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ClinicalTrials.gov Identifier: NCT01829295
Recruitment Status : Completed
First Posted : April 11, 2013
Results First Posted : April 26, 2019
Last Update Posted : April 26, 2019
Sponsor:
Collaborators:
Aravind Eye Hospitals, India
Oregon Health and Science University
Asociación para Evitar la Ceguera en México
Royal Victoria Eye and Ear Hospital
Northwestern University
National Eye Institute (NEI)
King Khaled Eye Specialist Hospital
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, the investigators propose to establish which immunosuppressive therapy, methotrexate or mycophenolate mofetil, is more effective as a first-line, corticosteroid-sparing agent for the treatment of non-infectious uveitis in a block-randomized, observer-masked, comparative effectiveness trial.

Condition or disease Intervention/treatment Phase
Uveitis Drug: Mycophenolate mofetil Drug: Methotrexate Drug: Prednisone Phase 3

Detailed Description:
This is a randomized comparative effectiveness trial to determine which treatment, methotrexate or mycophenolate mofetil, is more effective as first-line corticosteroid-sparing treatment for patients with non-infectious intermediate, posterior and panuveitis requiring corticosteroid-sparing therapy. The primary outcome is treatment success assessed at the 6 month visit (Phase 1, 0-6 months). If patients are a treatment success, they continue on the medication for another 6 months (Phase 1, 6-12 months). Patients who are a treatment failure can crossover to the other medication (Phase 2, 0-6 months).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 216 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial
Study Start Date : August 2013
Actual Primary Completion Date : February 21, 2018
Actual Study Completion Date : August 9, 2018


Arm Intervention/treatment
Experimental: Methotrexate
oral methotrexate
Drug: Methotrexate
For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week)

Drug: Prednisone
All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.

Experimental: Mycophenolate Mofetil
oral mycophenolate mofetil
Drug: Mycophenolate mofetil
For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID.
Other Name: Cellcept

Drug: Prednisone
All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.




Primary Outcome Measures :
  1. Treatment Success [ Time Frame: 6 Months ]
    Controlled ocular inflammation (≤ 0.5+ anterior chamber cells, ≤ 0.5+ vitreous haze, no active retinal/choroidal lesions in both eyes) with 7.5 mg/day of oral prednisone and ≤ 2 drops/day of topical 1% prednisolone acetate.



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All the following criteria must be met at enrollment:

Historical non-infectious intermediate, anterior and intermediate, posterior or panuveitis in at least one eye

Active inflammation within the last 180 days, defined by the presence of any of the following (in at least one eye) according to SUN criteria:

  • ≥ 2+ anterior chamber cells
  • ≥ 2+ vitreous haze
  • active retinal or choroidal lesions

Active inflammation at enrollment, defined by the presence of any of the following (in at least one eye) according to SUN criteria:

  • ≥1+ anterior chamber cells and/or
  • ≥1+ vitreous haze and/or
  • active retinal/choroidal lesions

At least one of the following criteria must be met before or at enrollment:

  • Active inflammation after 4 weeks of high-dose (1mg/kg prednisone equivalent) corticosteroid treatment or 4 weeks following a regional corticosteroid injection
  • Treatment with oral corticosteroids resulting in a reduction of inflammation, followed by an increase in inflammation (of at least 1 grade in anterior chamber cells or vitreous haze or a change of non-active to active lesions) when corticosteroid is tapered, in the 180 weeks prior to enrollment
  • Active inflammation after long-acting corticosteroid injection 4 weeks to 180 days prior to enrollment
  • Active inflammation after treatment with >10mg/day oral prednisone for at least the past 90 days prior to enrollment
  • Known chronic condition necessitating corticosteroid-sparing immunosuppressive treatment: Behcet's disease with posterior segment involvement, multifocal choroiditis with panuveitis, serpiginous choroidopathy, birdshot retinochoroidopathy, diffuse retinal vasculitis, Vogt-Koyanagi-Harada with bullous serous retinal detachments and/or choroidal detachments, sympathetic ophthalmia. No prior therapy required for these patients

Willingness to start corticosteroid treatment at 1mg/kg or 60mg a day of prednisone, whichever is less

Willingness to limit alcohol consumption

Willingness to use an acceptable method of contraception during the study period (i.e. pharmacologics, devices, barrier methods) or abstinence.

  • Exclusion Criteria: Any of the following

Any infectious cause of uveitis

Prior immunosuppressive therapy other than corticosteroids in the past 12 months

Prior intolerability or safety issues with methotrexate or mycophenolate mofetil

Prior failure to control ocular or other inflammation using methotrexate or mycophenolate mofetil

Prior biologic therapy at any time

Media opacity (such as cataract and/or corneal scar) and/or extensive posterior synechiae such that examination of the posterior segment is not possible in both eyes

Chronic hypotony (IOP < 5 mm Hg for > 3 months) in both eyes

Periocular or intravitreal corticosteroid injection in the past 4 weeks

Fluocinolone acetonide implant in either eye in < 3 years

Intraocular surgery in < 30 days, or planning on getting surgery within the next 6 months

Best spectacle-corrected visual acuity (BSCVA) of hand motions or worse in better eye

< 16 years of age at enrollment

Planning to conceive during the study period, pregnant or breast-feeding (blood or urine pregnancy test for all females, excluding those who are post-menopausal is mandatory)*

Any history of cancer (If a patient has a history of non-melanoma skin cancer they can still be considered for inclusion in this study, provided it is not currently active).

Systemic autoimmune disease anticipated to dictate treatment course

Abnormal Complete blood count (≤ 2,500 white blood cells and/or ≤ 75,000 platelets and/or ≤9 hemoglobin) within 4 weeks prior to enrollment*

Abnormal alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 2 times the upper limit of normal for the lab and/or creatinine ≥ 1.5 within 4 weeks prior to enrollment*

Evidence of active tuberculosis, HIV infection, syphilis, or hepatitis B or C (patients must have a tuberculin skin test, or interferon-gamma release assay, a chest radiograph, RPR/VDRL, FTA-ABS, or other treponemal tests, Hepatitis B surface antigen, Hepatitis C antibody tests, and HIV test within 90 days prior to enrollment)**

*Testing required within 4 weeks prior to enrollment; **Testing required within 90 days prior to enrollment.


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): NCT01829295


Locations
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United States, California
Francis I Proctor Foundation
San Francisco, California, United States, 94143
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Oregon
Oregon Health and Science University - Casey Eye Institute
Portland, Oregon, United States, 97239
Australia, Victoria
Royal Victorian Eye and Ear Hospital
Melbourne, Victoria, Australia, 3002
India
Aravind Eye Hospital
Coimbatore, Tamil Nadu, India
Aravind Eye Hospital
Madurai, Tamil Nadu, India
Aravind Eye Hospital
Pondicherry, Tamil Nadu, India
Mexico
Asociacion Para Evita La Ceguera en Mexico
Mexico City, Mexico, D.F., Mexico, 04030
Saudi Arabia
King Khaled Eye Specialist Hospital
Riyadh, Saudi Arabia
Sponsors and Collaborators
University of California, San Francisco
Aravind Eye Hospitals, India
Oregon Health and Science University
Asociación para Evitar la Ceguera en México
Royal Victoria Eye and Ear Hospital
Northwestern University
National Eye Institute (NEI)
King Khaled Eye Specialist Hospital
Investigators
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Principal Investigator: Nisha Acharya, MD, MS University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by University of California, San Francisco:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01829295     History of Changes
Other Study ID Numbers: 11-08227
5U10EY021125 ( U.S. NIH Grant/Contract )
First Posted: April 11, 2013    Key Record Dates
Results First Posted: April 26, 2019
Last Update Posted: April 26, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of California, San Francisco:
antimetabolite, noninfectious
Additional relevant MeSH terms:
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Uveitis
Uveal Diseases
Eye Diseases
Mycophenolic Acid
Prednisone
Methotrexate
Antimetabolites
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents