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Multicenter Uveitis Steroid Treatment (MUST) Trial (MUST)

This study has been completed.
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
JHSPH Center for Clinical Trials
ClinicalTrials.gov Identifier:
NCT00132691
First received: August 19, 2005
Last updated: June 22, 2012
Last verified: June 2012
  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:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Macular Edema [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    center point macular thickness >= 240 micrometers assessed on OCT (Stratus OCT-3 [Carl Zeiss Meditec, Dublin, CA]) as graded by Central Reading Center

  • Uveitis Activity [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Intraocular Pressure - Incident IOP Greater Than or Equal to 30 mm Hg [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Intraocular Pressure - Incident IOP Greater Than or Equal to 24 mm Hg [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Intraocular Pressure - Incident IOP Elevation >= 10 mmHg Above Baseline [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Glaucoma - Incident [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Glaucoma was diagnosed by a glaucoma specialist through review of visual fields, clinical data, and fundus images.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Intraocular Pressure - IOP-lowering Surgery [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Cataract - Incident Cataract [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Change in SF-36 Mental Component Score From Baseline to 24 Months [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Change in SF-36 Physical Component Score From Baseline to 24 Months [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Hyperlipidemia - Incident [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    LDL greater than or equal to 160 mg/mL

  • Hypertension Diagnosis Requiring Treatment [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Diabetes Mellitus [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Mortality [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

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
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 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   (Child, Adult, Senior)
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
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, see Learn About Clinical Studies.

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 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
  More Information

Additional Information:
Publications:
The Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Writing Committee, 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):1916-1926. Epub 2011 Aug 15. PubMed PMID: 21840602; PubMed Central PMCID: PMC3191365. http://dx.doi.org/ doi:10.1016/j.ophtha.2011.07.027

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

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
Results First Received: May 14, 2012
Last Updated: June 22, 2012
Health Authority: United States: Food and Drug Administration

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
Cyclophosphamide
Methotrexate
Mycophenolate mofetil
Azathioprine
Immunosuppressive Agents
Chlorambucil
Alkylating Agents
Mycophenolic Acid
Fluocinolone Acetonide
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Antibiotics, Antineoplastic
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 28, 2016