Multicenter Uveitis Steroid Treatment (MUST) Trial (MUST)

October 13, 2016 updated by: JHSPH Center for Clinical Trials
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

The MUST Research Group received additional funding at the completion of the MUST Trial to continue following patients enrolled in the study for an additional 7 years in the MUST Trial Follow-up Study (MUST FS). Since uveitis is often a chronic condition requiring long-term treatment, the objectives of the MUST FS are to evaluate outcomes of the two treatments over a longer period time. The outcomes specified for MUST FS are the same as those specified for the MUST Trial: visual acuity, ocular and systemic side effects of treatment, quality of life, and control of ocular inflammation. The primary analyses will be to compare outcomes between the original randomization groups, i.e., intention-to-treat. Secondary analyses will be based on treatment received. Study visits will be conducted every 6 months in MUST FS as opposed to every 3 months in the MUST Trial. Two analyses are planned for public release, one at 4.5 years and one after 7 years of follow-up. The Data Safety Monitoring Board reviewed and approved the analysis plan.

Study Type

Interventional

Enrollment (Actual)

255

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • East Melbourne, Australia
        • Royal Victoria Eye & Ear Hospital
  • United Kingdom
      • London, United Kingdom, EC1V 9EL
        • United Kingdom Institute of Ophthalmology
  • United States
    • California
      • La Jolla, California, United States, 92037
        • Jacobs Retina Center, UCSD
      • Los Angeles, California, United States, 90033
        • Doheny Eye Institute, USC
      • Los Angeles, California, United States, 90095
        • Jules Stein Eye Institute, UCLA
      • San Francisco, California, United States, 94143
        • Proctor Foundation, UCSF
    • Florida
      • Miami, Florida, United States, 33136
        • Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine
      • Tampa, Florida, United States, 33612
        • University of South Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago Eye Center
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Wilmer Eye Institute, Johns Hopkins University
      • Bethesda, Maryland, United States, 20892
        • National Eye Institute, NIH
    • Massachusetts
      • Cambridge, Massachusetts, United States, 02142
        • Massachusetts Eye Research & Surgery Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • Kellogg Eye Center, University of Michigan
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Barnes Retina Institute
    • New York
      • New York, New York, United States, 10016
        • New York Eye and Ear Infirmary
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Eye Center, Duke University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Scheie Eye Institute, University of Pennsylvania
    • Texas
      • Dallas, Texas, United States, 75231
        • Texas Retina Associates
      • Houston, Texas, United States, 77030
        • Vitreoretinal Consultants
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • John A. Moran Eye Center, University of Utah
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Virginia Eye Consultants

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
Immunosuppressant 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 Names:
  • 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:
  • tacrolimus
  • 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)
  • - Biologics
  • infliximab
  • daclizumab
  • other biologics

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Best-corrected Visual Acuity (Change in the Numbers of Letters Read From a Standard ETDRS Eye Chart) From Baseline to 24 Months in Eyes With Uveitis
Time Frame: 24 months
Best-corrected visual acuity was measured as the number of letters read from standard logarithmic visual acuity charts by study-certified examiners who were masked to treatment. Visual acuity was measured at all study visits. The primary outcome was eye-specific change in visual acuity from baseline to 2-year follow-up. Positive change values indicate improved vision while negative change values indicate vision has gotten worse. A change of 7.5 letters is considered clinically meaningful.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Macular Edema
Time Frame: 24 months
center point macular thickness >= 240 micrometers assessed on OCT (Stratus OCT-3 [Carl Zeiss Meditec, Dublin, CA]) as graded by Central Reading Center
24 months
Uveitis Activity
Time Frame: 24 months
Uveitis activity was determined by clinician assessment at each study visit. The study ophthalmologist evaluated each eye as active, inactive/never had uveitis or cannot assess.
24 months
Intraocular Pressure - Incident IOP Greater Than or Equal to 30 mm Hg
Time Frame: 24 months
24 months
Intraocular Pressure - Incident IOP Greater Than or Equal to 24 mm Hg
Time Frame: 24 months
24 months
Intraocular Pressure - Incident IOP Elevation >= 10 mmHg Above Baseline
Time Frame: 24 months
24 months
Glaucoma - Incident
Time Frame: 24 months
Glaucoma was diagnosed by a glaucoma specialist through review of visual fields, clinical data, and fundus images.
24 months
Intraocular Pressure (IOP) - Incident Use of IOP-lowering Medical Therapy (Percentage of Eyes With Uveitis That Were Not Being Treated With IOP-lowering Medical Therapy at Baseline and Underwent IOP Lowering Therapy During the 24 Month Follow-up.
Time Frame: 24 months
The percentage of subjects who used topical or systemic treatment for elevated IOP at any time during the 2 year follow-up and were not on IOP-lowering therapy at baseline is reported.
24 months
Intraocular Pressure - IOP-lowering Surgery
Time Frame: 24 months
24 months
Cataract - Incident Cataract
Time Frame: 24 months
24 months
Change in Self-reported Vision-related Function as Measured by the National Eye Institute 25-Item Visual Function Questionnaire (NEI-VFQ 25) Vision Targeted Composite Score From Baseline to 24 Months
Time Frame: 24 months
The NEI-VFQ 25 measures the effect of visual disability/symptoms with generic health and task-oriented domains. The range for the composite score is 0 to 100; higher scores are associated with better visual function. A change of 4 to 6 points is considered to be a clinically meaningful difference.
24 months
Change in SF-36 Mental Component Score From Baseline to 24 Months
Time Frame: 24 months
Self-reported health related QoL was measured with the SF 36 survey. The mental component score for the SF 36 is a summary measure of mental health primarily based on the social functioning, role emotional, mental health and vitality domains. The score is scaled to a population norm with a mean of 50 and standard deviation of 10. Higher scores represent better outcomes. The mean change in scores between baseline and 24 months was calculated for each treatment group.
24 months
Change in SF-36 Physical Component Score From Baseline to 24 Months
Time Frame: 24 months
Self-reported health related QoL was measured with the SF 36 survey. The physical component score for the SF 36 is a summary measure of physical health primarily based on the physical functioning, role physical, bodily pain and general health domains of the survey. The score is scaled to a population norm with a mean of 50 and standard deviation of 10. Higher scores represent better outcomes. The mean change in scores between baseline and 24 months was calculated for each treatment group. A 3 to 5 point difference is considered to be clinically meaningful.
24 months
Hyperlipidemia - Incident
Time Frame: 24 months
LDL greater than or equal to 160 mg/mL
24 months
Hypertension Diagnosis Requiring Treatment
Time Frame: 24 months
24 months
Diabetes Mellitus
Time Frame: 24 months
24 months
Mortality
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

JHSPH Center for Clinical Trials

Collaborators

National Eye Institute (NEI)

Investigators

  • Study Chair: Douglas Jabs, MD, MBA, Icahn School of Medicine at Mount Sinai
  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

August 19, 2005

First Submitted That Met QC Criteria

August 19, 2005

First Posted (Estimate)

August 22, 2005

Study Record Updates

Last Update Posted (Estimate)

November 25, 2016

Last Update Submitted That Met QC Criteria

October 13, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NEI-106
  • U10EY014660 (U.S. NIH Grant/Contract)
  • 1U10EY014660-2
  • ISRCTN15396562

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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