Clinical trial NCT00132691: Multicenter Uveitis Steroid Treatment (MUST) Trial
Official title: Multicenter Uveitis Steroid Treatment (MUST) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Uveitis
Keywords: uveitis
non-infectious intermediate uveitis
non-infectious posterior uveitis
non-infectious panuveitis
Lead sponsor: JHSPH Center for Clinical Trials
Sponsor class: OTHER
Collaborators: name: National Eye Institute (NEI)
First posted: 2005-08-22
Enrollment: 255
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 24 months
Secondary outcomes:
measure: Macular Edema
timeFrame: 24 months
measure: Uveitis Activity
timeFrame: 24 months
measure: Intraocular Pressure - Incident IOP Greater Than or Equal to 30 mm Hg
timeFrame: 24 months
measure: Intraocular Pressure - Incident IOP Greater Than or Equal to 24 mm Hg
timeFrame: 24 months
measure: Intraocular Pressure - Incident IOP Elevation >= 10 mmHg Above Baseline
timeFrame: 24 months
measure: Glaucoma - Incident
timeFrame: 24 months
measure: 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.
timeFrame: 24 months
measure: Intraocular Pressure - IOP-lowering Surgery
timeFrame: 24 months
measure: Cataract - Incident Cataract
timeFrame: 24 months
measure: 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
timeFrame: 24 months
measure: Change in SF-36 Mental Component Score From Baseline to 24 Months
timeFrame: 24 months
measure: Change in SF-36 Physical Component Score From Baseline to 24 Months
timeFrame: 24 months
measure: Hyperlipidemia - Incident
timeFrame: 24 months
measure: Hypertension Diagnosis Requiring Treatment
timeFrame: 24 months
measure: Diabetes Mellitus
timeFrame: 24 months
measure: Mortality
timeFrame: 24 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Jacobs Retina Center, UCSD
state: California
city: Los Angeles
country: United States
facility: Doheny Eye Institute, USC
state: California
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute, UCLA
state: California
city: San Francisco
country: United States
facility: Proctor Foundation, UCSF
state: California
city: Miami
country: United States
facility: Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago Eye Center
state: Illinois
city: Baltimore
country: United States
facility: Wilmer Eye Institute, Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: National Eye Institute, NIH
state: Maryland
city: Cambridge
country: United States
facility: Massachusetts Eye Research & Surgery Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Eye Center, University of Michigan
state: Michigan
city: St. Louis
country: United States
facility: Barnes Retina Institute
state: Missouri
city: New York
country: United States
facility: New York Eye and Ear Infirmary
state: New York
city: Durham
country: United States
facility: Duke Eye Center, Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: Scheie Eye Institute, University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: Houston
country: United States
facility: Vitreoretinal Consultants
state: Texas
city: Salt Lake City
country: United States
facility: John A. Moran Eye Center, University of Utah
state: Utah
city: Norfolk
country: United States
facility: Virginia Eye Consultants
state: Virginia
city: East Melbourne
country: Australia
facility: Royal Victoria Eye & Ear Hospital
city: London
country: United Kingdom
facility: United Kingdom Institute of Ophthalmology
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Douglas Jabs, MD, MBA
role: STUDY_CHAIR
affiliation: Scheie Eye Center, University of Pennsylvania
name: John Kempen, MD, PhD
role: STUDY_CHAIR
affiliation: Director of Coordinating Cener, Johns Hopkins Bloomberg School of Public Health
name: Janet T Holbrook, PhD, MPH
role: STUDY_DIRECTOR
affiliation: Director of Fundus Photography Reading Center, University of Wisconsin at Madison
name: Michael Altaweel, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.