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CompletedNCT00132691MUSTUpdated Nov 25, 2016Results posted

Multicenter Uveitis Steroid Treatment (MUST) Trial

A Phase 4 interventional study of fluocinolone acetonide intraocular implant and oral corticosteroid with immunosuppressive agents as needed in Uveitis, sponsored by JHSPH Center for Clinical Trials. Completed at 23 sites in 3 countries. Open to participants aged 13 Years and older. Per ClinicalTrials.gov, last updated 2016-11-25.

Sponsored by JHSPH Center for Clinical Trials · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
255
Allocation
Randomized
Ages
13 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Uveitis

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Keywords

  • uveitis
  • non-infectious intermediate uveitis
  • non-infectious posterior uveitis
  • non-infectious panuveitis
03

In context

Uveitis

335 studies on the registry are indexed under Uveitis; 37 are open to participants now.

This study's enrollment of 255 is above the median of 30 across 208 interventional studies indexed under Uveitis.

Browse Uveitis studies →

Lead sponsor

JHSPH Center for Clinical Trials is the lead sponsor of 13 studies on the registry; 3 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
13 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
255 participants (actual)

Study arms

  • Active comparator
    1

    Immunosuppressant medication implant

    Drug: fluocinolone acetonide intraocular implant

  • Active comparator
    2

    Systemic corticosteroids with immunosuppressant drugs as needed

    Drug: oral corticosteroid with immunosuppressive agents as needed

Interventions

  • Drugfluocinolone 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.

    Also known as: NDC 24208-416-01

  • Drugoral corticosteroid with immunosuppressive agents as needed

    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

06

What researchers measure

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.

    Time frame: 24 months

Secondary outcomes

  1. Macular Edema

    center point macular thickness \>= 240 micrometers assessed on OCT (Stratus OCT-3 \[Carl Zeiss Meditec, Dublin, CA\]) as graded by Central Reading Center

    Time frame: 24 months

  2. Uveitis Activity

    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.

    Time frame: 24 months

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

    Time frame: 24 months

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

    Time frame: 24 months

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

    Time frame: 24 months

  6. Glaucoma - Incident

    Glaucoma was diagnosed by a glaucoma specialist through review of visual fields, clinical data, and fundus images.

    Time frame: 24 months

  7. 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.

    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.

    Time frame: 24 months

  8. Intraocular Pressure - IOP-lowering Surgery

    Time frame: 24 months

  9. Cataract - Incident Cataract

    Time frame: 24 months

  10. 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

    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.

    Time frame: 24 months

  11. Change in SF-36 Mental Component Score From Baseline to 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.

    Time frame: 24 months

  12. Change in SF-36 Physical Component Score From Baseline to 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.

    Time frame: 24 months

  13. Hyperlipidemia - Incident

    LDL greater than or equal to 160 mg/mL

    Time frame: 24 months

  14. Hypertension Diagnosis Requiring Treatment

    Time frame: 24 months

  15. Diabetes Mellitus

    Time frame: 24 months

  16. Mortality

    Time frame: 24 months

07

Results

Posted Jul 30, 2012

Participant flow

Eligible patients were enrolled at 23 uveitis centers in the US, the United Kingdom and Australia from 6 December 2005 to 9 December 2008.

Participant flow — Overall Study
MilestoneFlucinolone Acetonide Intraocular ImplantStandard Systemic Treatment
Started129126
Completed118114
Not completed1112
Withdrew: Lost to follow-up58
Withdrew: Missed 2-year visit44
Withdrew: Death20

Outcome measures

PrimaryChange 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.

Time frame:
24 months
Reported as:
Mean · letters
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
lettersFlucinolone Acetonide ImplantSystemic Therapy
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 Uveitis6.0 ± 1.43.2 ± 1.4
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · Generalized estimating equations, linear · p = 0.16 (unadjusted) · Mean difference (net): 2.79 · 95% CI -1.16 to 6.68The treatment effect is a model-based comparison of within group treatment change from enrollment to 24 months (the difference of the differences - implant minus systemic).
SecondaryMacular Edema

center point macular thickness \>= 240 micrometers assessed on OCT (Stratus OCT-3 \[Carl Zeiss Meditec, Dublin, CA\]) as graded by Central Reading Center

Time frame:
24 months
Reported as:
Number · percentage of eyes with uveitis
Macular Edema
percentage of eyes with uveitisFlucinolone Acetonide ImplantSystemic Therapy
Macular Edema22 (14 to 30)30 (21 to 40)
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · GEE, logistic · p = 0.071 (unadjusted) · Ratio of odds ratios: 0.61 · 95% CI 0.34 to 1.03For each treatment group the odds of macular edema at 2 yrs as compared to baseline was computed. The treatment effect is the ratio of these odds (implant divided by systemic).
SecondaryUveitis Activity

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.

Time frame:
24 months
Reported as:
Number · percentage of eyes with uveitis
Uveitis Activity
percentage of eyes with uveitisFluocinolone Acetonide ImplantSystemic Therapy
Uveitis Activity12 (06 to 20)29 (21 to 39)
Statistical analysis
  • Fluocinolone Acetonide Implant vs Systemic Therapy · GEE, logistic · p = 0.001 (unadjusted) · Ratio of odds ratios: .29 · 95% CI .13 to .60For each treatment group the odds of uveitis activity at 2 years as compared to baseline was computed. The treatment effect represents the ratio of these odds (implant divided by systemic).
SecondaryIntraocular Pressure - Incident IOP Greater Than or Equal to 30 mm Hg
Time frame:
24 months
Reported as:
Number · percentage of eyes with uveitis at risk
Intraocular Pressure - Incident IOP Greater Than or Equal to 30 mm Hg
percentage of eyes with uveitis at riskFlucinolone Acetonide ImplantSystemic Therapy
Intraocular Pressure - Incident IOP Greater Than or Equal to 30 mm Hg32.8 (27.1 to 39.2)6.3 (3.7 to 10.3)
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · Cox proportional hazards w/ RE · p = <.0001 (unadjusted) · Hazard ratio (hr): 6.08 · 95% CI 3.32 to 11.15A Cox proportional hazards model with a random effect to account for between-eye correlation was used to estimate the relative hazard of experiencing an IOP of 30 mmHg or greater. The systemic arm was the reference group.
SecondaryIntraocular Pressure - Incident IOP Greater Than or Equal to 24 mm Hg
Time frame:
24 months
Reported as:
Number · percentage of eyes with uveitis at risk
Intraocular Pressure - Incident IOP Greater Than or Equal to 24 mm Hg
percentage of eyes with uveitis at riskFlucinolone Acetonide ImplantSystemic Therapy
Intraocular Pressure - Incident IOP Greater Than or Equal to 24 mm Hg53.1 (46.9 to 59.7)18.7 (14.2 to 24.5)
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · Cox proportional hazards w/ RE · p = <.0001 (unadjusted) · Hazard ratio (hr): 3.59 · 95% CI 2.34 to 5.50A Cox proportional hazards model with a random effect to account for between-eye correlation was used to estimate the relative hazard of experiencing an IOP of 24 mmHg or greater. The systemic arm was the reference group
SecondaryIntraocular Pressure - Incident IOP Elevation >= 10 mmHg Above Baseline
Time frame:
24 months
Reported as:
Number · percentage of eyes with uveitis at risk
Intraocular Pressure - Incident IOP Elevation >= 10 mmHg Above Baseline
percentage of eyes with uveitis at riskFluocinolone Acetonide ImplantSystemic Therapy
Intraocular Pressure - Incident IOP Elevation >= 10 mmHg Above Baseline51.8 (45.5 to 58.3)15.5 (11.4 to 20.9)
Statistical analysis
  • Fluocinolone Acetonide Implant vs Systemic Therapy · Cox proportional hazards with RE · p = <.0001 (unadjusted) · Hazard ratio (hr): 4.28 · 95% CI 2.78 to 6.58A Cox proportional hazards model with a random effect to account for between-eye correlation was used to estimate the relative hazard of experiencing an IOP that was 10mmHg or greater than the baseline value. The systemic arm was the reference group.
SecondaryGlaucoma - Incident

Glaucoma was diagnosed by a glaucoma specialist through review of visual fields, clinical data, and fundus images.

Time frame:
24 months
Reported as:
Number · percentage of eyes with uveitis at risk
Glaucoma - Incident
percentage of eyes with uveitis at riskFluocinolone Acetonide ImplantSystemic Therapy
Glaucoma - Incident16.5 (12.1 to 22.2)4.0 (2.0 to 7.8)
Statistical analysis
  • Fluocinolone Acetonide Implant vs Systemic Therapy · Cox proportional hazards w/ RE · p = 0.0008 (unadjusted) · Hazard ratio (hr): 4.19 · 95% CI 1.82 to 9.63A Cox proportional hazards model with a random effect to account for between-eye correlation was used to estimate the relative hazard of developing glaucoma. The systemic arm was the reference group.
SecondaryIntraocular 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.

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.

Time frame:
24 months
Reported as:
Number · percentage of eyes with uveitis at risk
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.
percentage of eyes with uveitis at riskFlucinolone Acetonide ImplantSystemic Therapy
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.61.1 (54.3 to 67.8)20.1 (15.1 to 26.3)
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · Cox proportional hazards w/ RE · p = <.0001 (unadjusted) · Hazard ratio (hr): 4.16 · 95% CI 2.67 to 6.47A Cox proportional hazards model with a random effect to account for between-eye correlation was used to estimate the relative hazard of using an IOP-lowering therapy. The systemic arm was the reference group.
SecondaryIntraocular Pressure - IOP-lowering Surgery
Time frame:
24 months
Reported as:
Number · percentage of eyes with uveitis at risk
Intraocular Pressure - IOP-lowering Surgery
percentage of eyes with uveitis at riskFlucinolone Acetonide ImplantSystemic Therapy
Intraocular Pressure - IOP-lowering Surgery26.2 (21.0 to 32.4)3.7 (1.9 to 7.2)
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · Cox proportional hazards w/ RE · p = <0.0001 (unadjusted) · Hazard ratio (hr): 8.40 · 95% CI 3.39 to 20.82A Cox proportional hazards model with a random effect to account for between-eye correlation was used to estimate the relative hazard of having surgery to lower IOP. The systemic arm was the reference group.
SecondaryCataract - Incident Cataract
Time frame:
24 months
Reported as:
Number · percentage of eyes with uveitis at risk
Cataract - Incident Cataract
percentage of eyes with uveitis at riskFluocinolone Acetonide ImplantSystemic Therapy
Cataract - Incident Cataract90.7 (81.3 to 96.6)44.9 (32.3 to 59.8)
Statistical analysis
  • Fluocinolone Acetonide Implant vs Systemic Therapy · Cox proportional hazards w/ RE · p = <0.0001 (unadjusted) · Hazard ratio (hr): 4.12 · 95% CI 2.21 to 7.67A Cox proportional hazards model with a random effect to account for between-eye correlation was used to estimate the relative hazard of developing a cataract. The systemic arm was the reference group.
SecondaryChange 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

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.

Time frame:
24 months
Reported as:
Mean · units on a scale (composite score)
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
units on a scale (composite score)Fluocinolone Acetonide ImplantSystemic Therapy
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 Months11.44 ± 1.676.80 ± 1.58
Statistical analysis
  • Fluocinolone Acetonide Implant vs Systemic Therapy · GEE, linear · p = 0.043 (unadjusted) · Mean difference (net): 4.64 · 95% CI 0.14 to 9.15The treatment effect is a model-based comparison of within group treatment change from enrollment to 24 months (the difference of the differences - implant minus systemic).
SecondaryChange in SF-36 Mental Component Score From Baseline to 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.

Time frame:
24 months
Reported as:
Mean · units on a scale
Change in SF-36 Mental Component Score From Baseline to 24 Months
units on a scaleFlucinolone Acetonide ImplantSystemic Therapy
Change in SF-36 Mental Component Score From Baseline to 24 Months2.55 ± 1.11-1.1 ± 1.15
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · GEE, linear · p = 0.023 (unadjusted) · Mean difference (net): 3.62 · 95% CI 0.49 to 6.76The treatment effect is a model-based comparison of within group treatment change from enrollment to 24 months (the difference of the differences - implant minus systemic)
SecondaryChange in SF-36 Physical Component Score From Baseline to 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.

Time frame:
24 months
Reported as:
Mean · units on a scale
Change in SF-36 Physical Component Score From Baseline to 24 Months
units on a scaleFlucinolone Acetonide ImplantSystemic Therapy
Change in SF-36 Physical Component Score From Baseline to 24 Months1.15 ± 0.83-1.8 ± 0.90
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · Generalized Estimating Equations · p = 0.016 (unadjusted) · Mean difference (net): 2.95 · 95% CI 0.54 to 5.36The treatment effect is a model-based comparison of within group treatment change from enrollment to 24 months (the difference of the differences - implant minus systemic).
SecondaryHyperlipidemia - Incident

LDL greater than or equal to 160 mg/mL

Time frame:
24 months
Reported as:
Number · percentage of participants at risk
Hyperlipidemia - Incident
percentage of participants at riskFlucinolone Acetonide ImplantSystemic Therapy
Hyperlipidemia - Incident9.8 (5.2 to 18.0)11.0 (6.3 to 19.1)
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · Regression, Cox · p = 0.84 (unadjusted) · Hazard ratio (hr): 0.91 · 95% CI 0.39 to 2.15A Cox proportional hazards model was used to evaluate the relative hazard of hyperlipidemia for the implant and systemic treatments. The systemic treatment is the reference group.
SecondaryHypertension Diagnosis Requiring Treatment
Time frame:
24 months
Reported as:
Number · percentage of participants
Hypertension Diagnosis Requiring Treatment
percentage of participantsFlucinolone Acetonide ImplantSystemic Therapy
Hypertension Diagnosis Requiring Treatment4.6 (1.8 to 11.9)10.5 (5.6 to 19.3)
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · Regression, Cox · p = 0.13 (unadjusted) · Hazard ratio (hr): 0.40 · 95% CI 0.13 to 1.29A Cox proportional hazards model was used to evaluate the relative hazard of hypertension for the implant and systemic treatments. The systemic treatment is the reference group.
SecondaryDiabetes Mellitus
Time frame:
24 months
Reported as:
Number · percentage of participants
Diabetes Mellitus
percentage of participantsFlucinolone Acetonide ImplantSystemic Therapy
Diabetes Mellitus1.0 (0.1 to 6.6)3.6 (1.4 to 9.4)
Statistical analysis
  • Flucinolone Acetonide Implant vs Systemic Therapy · Regression, Cox · p = 0.24 (unadjusted) · Hazard ratio (hr): 0.26 · 95% CI 0.03 to 2.44A Cox proportional hazards model was used to evaluate the relative hazard of diabetes mellitus for the implant and systemic treatments. The systemic treatment is the reference group.
SecondaryMortality
Time frame:
24 months
Reported as:
Number · percentage of participants
Mortality
percentage of participantsFlucinolone Acetonide ImplantSystemic Therapy
Mortality1.6 (0.4 to 6.3)0 (NA to NA)

Adverse events

Collected over 2 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Flucinolone Acetonide Implant—75/129 (58.1%)113/129 (87.6%)
Systemic Therapy—47/126 (37.3%)113/126 (89.7%)
Most frequent serious events
Showing 10 of 61
Most frequent serious events
EventFlucinolone Acetonide ImplantSystemic Therapy
Ocular HypertensionEye disorders32/1295/126
Vitreous HemorrhageEye disorders14/1294/126
GlaucomaEye disorders7/1291/126
HypertensionCardiac disorders7/1293/126
FractureInjury, poisoning and procedural complications1/1296/126
InfectionInfections and infestations6/1295/126
CardiovascularCardiac disorders2/1294/126
HypotonyEye disorders4/1292/126
Retinal DetachmentEye disorders4/1291/126
Abnormal laboratory valueHepatobiliary disorders4/1291/126
Most frequent other events
Showing 10 of 22
Most frequent other events
EventFlucinolone Acetonide ImplantSystemic Therapy
Ocular hypertensionEye disorders78/12929/126
InfectionGeneral disorders52/12967/126
CataractEye disorders40/12913/126
Hypertension (systolic)Cardiac disorders27/12932/126
Hypertension (diastolic)Cardiac disorders24/12930/126
HypotonyEye disorders26/12910/126
HeadacheGeneral disorders25/12919/126
NauseaGastrointestinal disorders5/12920/126
Vitreous hemorrhageEye disorders13/1292/126
DiarrheaGastrointestinal disorders2/12912/126

Baseline characteristics

Age, Continuous
Age, Continuous(years)Flucinolone Acetonide Intraocular ImplantStandard Systemic TreatmentTotal
Mean46 ± 1547 ± 1546 ± 15
Sex: Female, Male
Sex: Female, Male(Participants)Flucinolone Acetonide Intraocular ImplantStandard Systemic TreatmentTotal
Female91100191
Male382664
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Flucinolone Acetonide Intraocular ImplantStandard Systemic TreatmentTotal
White7270142
Hispanic181533
Black353166
Other41014
Region of Enrollment
Region of Enrollment(participants)Flucinolone Acetonide Intraocular ImplantStandard Systemic TreatmentTotal
United States109104213
Australia5611
United Kingdom151631
Bilateral uveitis
Bilateral uveitis(participants)Flucinolone Acetonide Intraocular ImplantStandard Systemic TreatmentTotal
Number116108224
Site of uveitis
Site of uveitis(participants)Flucinolone Acetonide Intraocular ImplantStandard Systemic TreatmentTotal
Intermediate504797
Posterior or Panuveitis7979158
Associated systemic inflammatory disease
Associated systemic inflammatory disease(participants)Flucinolone Acetonide Intraocular ImplantStandard Systemic TreatmentTotal
Yes363369
no9393186
Visual acuity 20/40 or better
Visual acuity 20/40 or better(eyes)Flucinolone Acetonide Intraocular ImplantStandard Systemic TreatmentTotal
Number116122238

2 further baseline measures are reported on the registry.

08

Study locations

23 sites
  • Jacobs Retina Center, UCSD
    La Jolla, California 92037, United States
  • Doheny Eye Institute, USC
    Los Angeles, California 90033, United States
  • Jules Stein Eye Institute, UCLA
    Los Angeles, California 90095, United States
  • Proctor Foundation, UCSF
    San Francisco, California 94143, United States
  • Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine
    Miami, Florida 33136, United States
  • University of South Florida
    Tampa, Florida 33612, United States
  • Emory University
    Atlanta, Georgia 30322, United States
  • Rush University Medical Center
    Chicago, Illinois 60612, United States
  • University of Illinois at Chicago Eye Center
    Chicago, Illinois 60612, United States
  • Wilmer Eye Institute, Johns Hopkins University
    Baltimore, Maryland 21287, United States
  • National Eye Institute, NIH
    Bethesda, Maryland 20892, United States
  • Massachusetts Eye Research & Surgery Institute
    Cambridge, Massachusetts 02142, United States
  • Kellogg Eye Center, University of Michigan
    Ann Arbor, Michigan 48105, United States
  • Barnes Retina Institute
    St. Louis, Missouri 63110, United States
  • New York Eye and Ear Infirmary
    New York, New York 10016, United States
  • Duke Eye Center, Duke University
    Durham, North Carolina 27710, United States
  • Scheie Eye Institute, University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • Texas Retina Associates
    Dallas, Texas 75231, United States
  • Vitreoretinal Consultants
    Houston, Texas 77030, United States
  • John A. Moran Eye Center, University of Utah
    Salt Lake City, Utah 84132, United States
  • Virginia Eye Consultants
    Norfolk, Virginia 23502, United States
  • Royal Victoria Eye & Ear Hospital
    East Melbourne, Australia
  • United Kingdom Institute of Ophthalmology
    London, EC1V 9EL, United Kingdom
09

References and documents

Publications

  • 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. Erratum In: Ophthalmology. 2012 Feb;119(2):212. PubMed 21840602 ↗
  • 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. PubMed 32918964 ↗
  • 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. PubMed 28477440 ↗
  • 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. PubMed 26798977 ↗
  • 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. PubMed 26501236 ↗
  • 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. PubMed 25115882 ↗
  • 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. PubMed 23163490 ↗
  • 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. PubMed 22409563 ↗
  • 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. PubMed 22247489 ↗
  • 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. PubMed 21861971 ↗
  • 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. PubMed 21652026 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 25, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00132691
Lead sponsor
JHSPH Center for Clinical Trials
Collaborators
National Eye Institute (NEI)
Responsible party
Sponsor
First posted
Aug 22, 2005
Start date
Sep 2005
Primary completion
Dec 2010
Completion
Dec 2010
Results posted
Jul 30, 2012
Last update
Nov 25, 2016

Study contacts

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

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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