Multicenter Uveitis Steroid Treatment (MUST) Trial

NCT00132691 | Completed Phase 4 Results DMC

• 4 other identifiers: NEI-106U10EY0146601U10EY014660-2ISRCTN15396562
• Study Type: interventional
• Target: 255
• Locations: 3 countries
• Sites: 23

Brief Summary

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.

Conditions

Uveitis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (16)

• Macular Edema

  24 months

• Uveitis Activity

  24 months

• Intraocular Pressure - Incident IOP Greater Than or Equal to 30 mm Hg

  24 months

• Intraocular Pressure - Incident IOP Greater Than or Equal to 24 mm Hg

  24 months

• Intraocular Pressure - Incident IOP Elevation >= 10 mmHg Above Baseline

  24 months

Study Arms (2)

1

ACTIVE COMPARATOR

Immunosuppressant medication implant

Drug: fluocinolone acetonide intraocular implant

2

ACTIVE COMPARATOR

Systemic corticosteroids with immunosuppressant drugs as needed

Drug: oral corticosteroid with immunosuppressive agents as needed

Interventions

fluocinolone acetonide intraocular implant DRUG

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.

Also known as: NDC 24208-416-01

1

oral corticosteroid with immunosuppressive agents as needed DRUG

Prednisone

Also known as: 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

2

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• JHSPH Center for Clinical Trials: lead
• National Eye Institute (NEI): collaborator

Study Sites (23)

Jacobs Retina Center, UCSD

La Jolla, California, 92037, United States

Location

Doheny Eye Institute, USC

Los Angeles, California, 90033, United States

Location

Jules Stein Eye Institute, UCLA

Los Angeles, California, 90095, United States

Location

Proctor Foundation, UCSF

San Francisco, California, 94143, United States

Location

Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois at Chicago Eye Center

Chicago, Illinois, 60612, United States

Location

Wilmer Eye Institute, Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

National Eye Institute, NIH

Bethesda, Maryland, 20892, United States

Location

Massachusetts Eye Research & Surgery Institute

Cambridge, Massachusetts, 02142, United States

Location

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Barnes Retina Institute

St Louis, Missouri, 63110, United States

Location

New York Eye and Ear Infirmary

New York, New York, 10016, United States

Location

Duke Eye Center, Duke University

Durham, North Carolina, 27710, United States

Location

Scheie Eye Institute, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Retina Associates

Dallas, Texas, 75231, United States

Location

Vitreoretinal Consultants

Houston, Texas, 77030, United States

Location

John A. Moran Eye Center, University of Utah

Salt Lake City, Utah, 84132, United States

Location

Virginia Eye Consultants

Norfolk, Virginia, 23502, United States

Location

Royal Victoria Eye & Ear Hospital

East Melbourne, Australia

Location

United Kingdom Institute of Ophthalmology

London, EC1V 9EL, United Kingdom

Location

Related Publications (11)

• 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. doi: 10.1016/j.ophtha.2011.07.027. Epub 2011 Aug 15.

  PMID: 21840602 RESULT

• Tomkins-Netzer O, Lightman SL, Burke AE, Sugar EA, Lim LL, Jaffe GJ, Altaweel MM, Kempen JH, Holbrook JT, Jabs DA; Multicenter Steroid Treatment Trial and Follow-up Study Research Group. Seven-Year Outcomes of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial and Follow-up Study Results. Ophthalmology. 2021 May;128(5):719-728. doi: 10.1016/j.ophtha.2020.08.035. Epub 2020 Sep 10.

  PMID: 32918964 DERIVED

• Writing Committee for the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group; Kempen JH, Altaweel MM, Holbrook JT, Sugar EA, Thorne JE, Jabs DA. Association Between Long-Lasting Intravitreous Fluocinolone Acetonide Implant vs Systemic Anti-inflammatory Therapy and Visual Acuity at 7 Years Among Patients With Intermediate, Posterior, or Panuveitis. JAMA. 2017 May 16;317(19):1993-2005. doi: 10.1001/jama.2017.5103.

  PMID: 28477440 DERIVED

• Yu T, Holbrook JT, Thorne JE, Puhan MA. Using a patient-centered approach to benefit-harm assessment in treatment decision-making: a case study in uveitis. Pharmacoepidemiol Drug Saf. 2016 Apr;25(4):363-71. doi: 10.1002/pds.3959. Epub 2016 Jan 22.

  PMID: 26798977 DERIVED

• Yu T, Holbrook JT, Thorne JE, Flynn TN, Van Natta ML, Puhan MA. Outcome Preferences in Patients With Noninfectious Uveitis: Results of a Best-Worst Scaling Study. Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6864-72. doi: 10.1167/iovs.15-16705.

  PMID: 26501236 DERIVED

• Drye LT, Casper AS, Sternberg AL, Holbrook JT, Jenkins G, Meinert CL. The transitioning from trials to extended follow-up studies. Clin Trials. 2014 Dec;11(6):635-47. doi: 10.1177/1740774514547396. Epub 2014 Aug 12.

  PMID: 25115882 DERIVED

• Domalpally A, Altaweel MM, Kempen JH, Myers D, Davis JL, Foster CS, Latkany P, Srivastava SK, Stawell RJ, Holbrook JT; MUST Trial Research Group. Optical coherence tomography evaluation in the Multicenter Uveitis Steroid Treatment (MUST) trial. Ocul Immunol Inflamm. 2012 Dec;20(6):443-7. doi: 10.3109/09273948.2012.719258. Epub 2012 Nov 19.

  PMID: 23163490 DERIVED

• 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. doi: 10.3109/09273948.2011.647228.

  PMID: 22409563 DERIVED

• 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. doi: 10.1167/iovs.11-8259. Print 2012 Mar.

  PMID: 22247489 DERIVED

• 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. doi: 10.1016/j.ajo.2011.05.028. Epub 2011 Sep 8.

  PMID: 21861971 DERIVED

• 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. doi: 10.1016/j.ajo.2011.01.058. Epub 2011 Jun 8.

  PMID: 21652026 DERIVED

Related Links

• MUST, JHU, Center for Clinical Trials
• ISRCTN15396562

MeSH Terms

Conditions

Uveitis

Interventions

Adrenal Cortex Hormones; Immunosuppressive Agents; Health Services Needs and Demand; Alkylating Agents; Cyclophosphamide; Azathioprine; Chlorambucil; Methotrexate; Mycophenolic Acid; Cyclosporine; Tacrolimus; Biological Products; Infliximab; Daclizumab

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Health Services Research; Health Planning; Health Care Economics and Organizations; Delivery of Health Care; Health Care Quality, Access, and Evaluation; Molecular Mechanisms of Pharmacological Action; Noxae; Toxic Actions; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Complex Mixtures; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized

Results Point of Contact

• Title: John H. Kempen, MD, PhD, MUST Trial Vice-Chairman
• Organization: Center for Presventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania

john.kempen@uphs.upenn.edu

215-615-1500

Study Officials

• Douglas Jabs, MD, MBA

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• John Kempen, MD, PhD

  Scheie Eye Center, University of Pennsylvania

  STUDY CHAIR

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2005
• First Posted: August 22, 2005
• Study Start: September 1, 2005
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: November 25, 2016
• Results First Posted: July 30, 2012

Record last verified: 2016-10

Locations

US (21); AU (1); GB (1)