Corticosteroid Implant vs. Oral Corticosteroid Treatment for Uveitis

Condition(s) targeted: Ocular Inflammation; Uveitis

Intervention: Fluocinolone Acetonide Implant (Device); Standard Systemic Immunotherapy (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: National Eye Institute (NEI)

Overall contact:
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

This study will test whether a new corticosteroid implant is more effective for reducing eye inflammation in patients with uveitis than the standard treatment with oral corticosteroids. Uveitis is an inflammation in the eye that, left untreated, can impair vision.

People 13 years of age or older with active, vision-threatening uveitis that is not caused by an infection and that would ordinarily require treatment with an oral corticosteroid may be eligible for this study. Candidates are screened with a medical history, blood tests, measurement of blood pressure, height and weight, bone density scans of the spine and hip, and an eye examination. The eye examination includes a test of vision and eye pressure, photographs of the eye lens, fluorescein angiography (photographs of blood vessels in the back of the eye), and optical coherence tomography. For the fluorescein angiography, a dye is injected through a vein in the arm or hand. It travels through the bloodstream to the blood vessels in the back of the eye. A series of pictures are taken that reveal the location and severity of inflammation in the back of the eye. Optical coherence tomography uses light to measure the thickness of the central part of the retina (back part of the eye) to look for swelling.

Participants are randomly assigned to receive oral corticosteroid treatment or the corticosteroid implant, as follows:

- Corticosteroid implant

Patients receive implants in one or both eyes, depending on whether one or both eyes need treatment. If both eyes are to receive implants, the second surgery is usually scheduled within 2 weeks after the first. The surgery is usually done under local anesthesia, with medication given through a vein to relax the patient and keep him or her comfortable during the procedure. A numbing medicine is injected around the eye to prevent pain. The implant is placed behind the iris (colored part of the eye), and a patch is placed over the eye until the day after the surgery. Patients are examined the day after surgery and once or twice more for checkups. The implant slowly releases a corticosteroid medicine called fluocinolone acetonide. It lasts about 2-1/2 years and can be replaced after that, if needed.

- Oral corticosteroids

Patients assigned to standard therapy take corticosteroids by mouth, with the dose being slowly decreased. If the dose cannot be reduced to a sufficiently low level because the inflammation returns, an immune-modulating drug is added to the treatment. Total treatment time varies, but, because uveitis often recurs, treatment may continue for two years or more.

OR

Patients assigned to standard therapy take corticosteroids by mouth, combined with other immunosuppressive agents, based on the individual patient's condition. The steroid dose is slowly decreased. Total treatment time varies, but, because uveitis often recurs, treatment may continue for two years or more.

In addition to their assigned treatment, patients may receive corticosteroid eye drops, ointments, or injections next to the eye as needed for the most effective control of swelling and inflammation.

Patients have clinic visits at weeks 4 and 12 after enrollment and every 12 weeks after that for up to 4 years. At each visit, patients provide a medical history, have an eye examination, complete questionnaires, have a blood test, and have their blood pressure and weight measured. They have fluorescein angiography and digital imaging of the eyes at weeks 4, 24, and 52 and then once a year. Color photographs of the eye are taken once a year. A scan of the spine and hip bones is done once a year. Visits to treat the uveitis may be required as often as once a month.

Official title: Multicenter Uveitis Steroid Treatment (MUST) Trial Protocol

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Compare the visual outcomes of patients with uveitis treated with the implant therapy to those treated with standard systemic immunotherapy.

Secondary outcome: Control of intraocular inflammation. Occurrence of ocular complicatins of uveitis/therapy. Occurrence of systemic complications of therapy.

Detailed description: Uveitis refers to several ocular disorders characterized by intraocular inflammation, which in the aggregate are a major cause of visual loss and blindness in the United States. Intermediate uveitis, posterior uveitis, and panuveitis are generally the more severe forms of uveitis, with the highest risk of vision loss, often requiring long-term systemic treatment. The fluocinolone acetonide intraocular implant is a surgically implanted reservoir of corticosteroid designed to last approximately 2. 5 years in order to provide long-term control of uveitis.

The primary objective of the Multicenter Uveitis Steroid Treatment (MUST) Trial is to compare the efficacy of standardized systemic therapy versus fluocinolone acetonide implant therapy for the treatment of severe cases of non-infectious intermediate uveitis, posterior uveitis or panuveitis. Patients with active uveitis will be randomized, with a 1: 1 allocation ratio, to treatment with either the fluocinolone acetonide implant or standardized systemic therapy consisting of oral corticosteroids and supplementary immunosuppressive drugs when indicated, according to standardized guidelines. The design outcome variable for the study is visual acuity; other outcomes include other aspects of visual function, success in controlling uveitis, retinal morphologic outcomes, quality of life, cost-effectiveness, and occurrence of potential ocular and systemic complications of uveitis and of therapy.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

- INCLUSION CRITERIA:

Age 18 years or older;

Diagnosis of active, recurrent, chronic non-infectious intermediate, posterior, or panuveitis that has required immunosusuppressive therapy for at least 3 months in the past year.

Active uveitis of a degree for which systemic corticosteroid therapy is indicated in the judgment of a MUST-certified ophthalmologist or such uveitis active within the last 60 days as determined either by examination by a MUST-certified ophthalmologist or by review of ophthalmic medical records by a MUST-certified ophthalmologist.

Uveitis with or without an associated systemic disease is acceptable; however, the systemic disease must not be sufficiently active that it dictates therapy with oral corticosteroids or immunosuppressive agents at the time of study entry;

Best-corrected visual acuity (BCVA) of hand mothions or better in at least one eye with uveitis.

Baseline intraocular pressure 24 mm Hg or less in all eyes with uveitis.

Collection of required baseline data within 10 days prior to randomization;

Signed informed consent.

EXCLUSION CRITERIA:

Diabetes mellitus that is inadequately controlled, according to best medical judgment;

A known allergy to a required study medication;

Uncontrolled glaucoma;

Advanced glaucomatous optic nerve injury meeting the following criteria:

For patients able to perform a Humphrey Visual Field

- Depression of two or more points within 10 degrees of fixation by at least 10 dB

and/or

- Mean deviation worse than -15 dB

For patients unable to perform a Humphrey Visual Field

- Vertical C/D greater than or equal to 0. 9

A history of scleritis (because of concerns regarding the potential for scleral melting with local corticosteroid therapy);

Presence of an ocular toxoplasmosis scar;

Pregnancy;

Current breastfeeding;

Known human immunodeficiency virus infection or other immunodeficiency disease for which corticosteroid therapy would be contraintraindicated according to best medical judgment;

Patients for whom participation in the trial would constitute a risk exceeding the potential benefits of study participation, in the judgment of the treating physician;

Medical problems or drug or alcohol dependence problems sufficient to prevent adherence to treatment and study procedures.

Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting

NIH Clinical Center Detailed Web Page

Related publications:

Perkins ES, Folk J. Uveitis in London and Iowa. Ophthalmologica. 1984;189(1-2):36-40.

Henderly DE, Genstler AJ, Smith RE, Rao NA. Changing patterns of uveitis. Am J Ophthalmol. 1987 Feb 15;103(2):131-6.

Palmares J, Coutinho MF, Castro-Correia J. Uveitis in northern Portugal. Curr Eye Res. 1990;9 Suppl:31-4.

Starting date: December 2005
Last updated: September 15, 2008