Multicenter Uveitis Steroid Treatment (MUST) Trial - Full Text View

Sponsor:	JHSPH Center for Clinical Trials
Collaborator:	National Eye Institute (NEI)
Information provided by (Responsible Party):	JHSPH Center for Clinical Trials
ClinicalTrials.gov Identifier:	NCT00132691

Purpose

The purpose of this study is to compare the effectiveness of standardized systemic therapy versus fluocinolone acetonide implant therapy for the treatment of severe cases of non-infectious intermediate uveitis, posterior uveitis, or panuveitis.

Condition	Intervention	Phase
Uveitis	Drug: fluocinolone acetonide intraocular implant Drug: oral corticosteroid with immunosuppressive agents as needed	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Multicenter Uveitis Steroid Treatment (MUST) Trial

Resource links provided by NLM:

Drug Information available for: Cyclophosphamide Methotrexate Fluocinolone acetonide Chlorambucil Azathioprine Methotrexate sodium Azathioprine Sodium Cyclosporine Tacrolimus Mycophenolate mofetil hydrochloride Mycophenolate mofetil Daclizumab Infliximab

U.S. FDA Resources

Further study details as provided by JHSPH Center for Clinical Trials:

Primary Outcome Measures:

difference in visual acuity [ Time Frame: at two years of follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Retinal morphology / Intraocular inflammation / Potential ocular complications of uveitis and of therapy / Potential systemic complications of therapy / Adverse event reporting [ Time Frame: On-going ] [ Designated as safety issue: Yes ]
Mortality / Cost-effectiveness / Quality of life [ Time Frame: On-going ] [ Designated as safety issue: No ]

Enrollment:	255
Study Start Date:	September 2005
Study Completion Date:	December 2010
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Immunosupressant medication implant	Drug: fluocinolone acetonide intraocular implant RETISERT™ (fluocinolone acetonide intravitreal implant) 0.59 mg is a sterile implant designed to release fluocinolone acetonide locally to the posterior segment of the eye at a nominal initial rate of 0.6 μg/day, decreasing over the first month to a steady state between 0.3-0.4 μg/day over approximately 30 months. Other Name: NDC 24208-416-01
Active Comparator: 2 Systemic corticosteroids with immunosuppressant drugs as needed	Drug: oral corticosteroid with immunosuppressive agents as needed Prednisone Other Names: Permitted immunosuppressive agents: - Alkylating agents cyclophosphamide (Cytoxan) chlorambacil - Antimetabolities azathioprine (Imuran) azathioprine chlorambucil (Leukeran) methotrexate (Rheumatrex and others) mycophenolate mofetil (Cellcept) - T-cell inhibitors cyclosporine (Neoral, Sandimmune and other trade names) tacrolimus - Biologics infliximab daclizumab other biologics

Arms

Assigned Interventions

Active Comparator: 1

Immunosupressant medication implant

Drug: fluocinolone acetonide intraocular implant

RETISERT™ (fluocinolone acetonide intravitreal implant) 0.59 mg is a sterile implant designed to release fluocinolone acetonide locally to the posterior segment of the eye at a nominal initial rate of 0.6 μg/day, decreasing over the first month to a steady state between 0.3-0.4 μg/day over approximately 30 months.

Other Name: NDC 24208-416-01

Active Comparator: 2

Systemic corticosteroids with immunosuppressant drugs as needed

Drug: oral corticosteroid with immunosuppressive agents as needed

Prednisone

Other Names:

Permitted immunosuppressive agents:
- Alkylating agents
cyclophosphamide (Cytoxan)
chlorambacil
- Antimetabolities
azathioprine (Imuran)
azathioprine chlorambucil (Leukeran)
methotrexate (Rheumatrex and others)
mycophenolate mofetil (Cellcept)
- T-cell inhibitors
cyclosporine (Neoral, Sandimmune and other trade names)
tacrolimus
- Biologics
infliximab
daclizumab
other biologics

Detailed Description:

The MUST trial is a randomized controlled clinical trial comparing two treatments for patients with vision-threatening non-infectious intermediate uveitis, posterior uveitis, or panuveitis:

local therapy with fluocinolone acetonide intraocular implant in affected eyes; versus
standard therapy: systemic corticosteroid therapy supplemented, when indicated, by corticosteroid-sparing potent immuno-modulator therapy.

Study ophthalmologists, clinic coordinators, and patients will not be masked to treatment assignment. Masking will be applied to the determination of visual function at baseline, the six month visit, and thereafter . Patients will be followed until death, participant withdrawal, or a common study closeout. Patients will be seen at baseline, one month after randomization, three months after randomization, and every three months thereafter for data collection. Both ophthalmological and medical data will be collected to evaluate the outcomes of treatment of the uveitis, complications of the uveitis, and complications from therapy itself. Selected laboratory data related to the complications from systemic corticosteroid therapy will be collected.

The planned sample size of 250 patients, 125 per treatment group, is expected to give sufficient power to detect clinically important differences in visual acuity outcomes. Patients meeting the eligibility criteria detailed above will be enrolled at approximately 23 clinical centers in the United States, Australia and UK. Patients will be randomized on a 1:1 basis to one of the two treatment groups.

Eligibility

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 13 years or older
Best-corrected visual acuity of hand motions or better in at least one eye with uveitis
Intraocular pressure 24 mm Hg or less in all eyes with uveitis

Exclusion Criteria:

Inadequately controlled diabetes
Uncontrolled glaucoma
Advanced glaucomatous optic nerve injury
A history of scleritis; presence of an ocular toxoplasmosis scar.
HIV infection or other immunodeficiency disease for which corticosteroid therapy would be contraindicated according to best medical judgment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00132691

Show 23 Study Locations

Sponsors and Collaborators

JHSPH Center for Clinical Trials

National Eye Institute (NEI)

Investigators

Study Chair:	Douglas Jabs, MD, MBA	Mount Sinai School of Medicine
Study Chair:	John Kempen, MD, PhD	Scheie Eye Center, University of Pennsylvania
Study Director:	Janet T Holbrook, PhD, MPH	Director of Coordinating Cener, Johns Hopkins Bloomberg School of Public Health
Study Director:	Michael Altaweel, MD	Director of Fundus Photography Reading Center, University of Wisconsin at Madison

More Information

Additional Information:

MUST, JHU, Center for Clinical Trials This link exits the ClinicalTrials.gov site

ISRCTN15396562 This link exits the ClinicalTrials.gov site

No publications provided by JHSPH Center for Clinical Trials

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sen HN, Drye LT, Goldstein DA, Larson TA, Merrill PT, Pavan PR, Sheppard JD, Burke A, Srivastava SK, Jabs DA; Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group. Hypotony in patients with uveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial. Ocul Immunol Inflamm. 2012 Apr;20(2):104-12.

Frick KD, Drye LT, Kempen JH, Dunn JP, Holland GN, Latkany P, Rao NA, Sen HN, Sugar EA, Thorne JE, Wang RC, Holbrook JT; Multicenter Uveitis Steroid Treatment-MUST Trial Research Group. Associations among visual acuity and vision- and health-related quality of life among patients in the multicenter uveitis steroid treatment trial. Invest Ophthalmol Vis Sci. 2012 Mar 9;53(3):1169-76. Print 2012.

Sugar EA, Jabs DA, Altaweel MM, Lightman S, Acharya N, Vitale AT, Thorne JE; Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group. Identifying a clinically meaningful threshold for change in uveitic macular edema evaluated by optical coherence tomography. Am J Ophthalmol. 2011 Dec;152(6):1044-1052.e5. Epub 2011 Sep 8.

Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Louis TA, Sugar EA, Thorne JE. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial. Ophthalmology. 2011 Oct;118(10):1916-26. Epub 2011 Aug 15.

Madow B, Galor A, Feuer WJ, Altaweel MM, Davis JL. Validation of a photographic vitreous haze grading technique for clinical trials in uveitis. Am J Ophthalmol. 2011 Aug;152(2):170-176.e1. Epub 2011 Jun 8.

Responsible Party:	JHSPH Center for Clinical Trials
ClinicalTrials.gov Identifier:	NCT00132691 History of Changes
Obsolete Identifiers:	NCT00269698
Other Study ID Numbers:	NEI-106, U10EY014660, 1U10EY014660-2, ISRCTN15396562
Study First Received:	August 19, 2005
Last Updated:	October 26, 2011
Health Authority:	United States: Federal Government

Keywords provided by JHSPH Center for Clinical Trials:

uveitis
non-infectious intermediate uveitis
non-infectious posterior uveitis
non-infectious panuveitis

Additional relevant MeSH terms:

Uveitis
Uveal Diseases
Eye Diseases
Alkylating Agents
Cyclophosphamide
Azathioprine
Immunosuppressive Agents
Mycophenolate mofetil
Fluocinolone Acetonide
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites

Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 24, 2012