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Multicenter Uveitis Steroid Treatment (MUST) Trial (MUST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00132691
Recruitment Status : Completed
First Posted : August 22, 2005
Results First Posted : July 30, 2012
Last Update Posted : November 25, 2016
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
JHSPH Center for Clinical Trials

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Uveitis
Interventions Drug: fluocinolone acetonide intraocular implant
Drug: oral corticosteroid with immunosuppressive agents as needed
Enrollment 255
Recruitment Details Eligible patients were enrolled at 23 uveitis centers in the US, the United Kingdom and Australia from 6 December 2005 to 9 December 2008.
Pre-assignment Details 579 patients were assessed for initial eligibility (e.g. through chart review). Patients who were potentially eligible and interested in joining the trial signed an informed consent and underwent a baseline visit to confirm eligibility. Eligible patients (255) were randomly assigned to systemic treatment or implant treatment.
Arm/Group Title Flucinolone Acetonide Intraocular Implant Standard Systemic Treatment
Hide Arm/Group Description Local therapy with fluocinolone acetonide 0.59 mg implant (Retisert; Bausch & Lomb Inc.) in each eye with uveitis of sufficient severity to justify treatment with systemic corticosteroids Systemic corticosteroid therapy with immunosuppression as indicated
Period Title: Overall Study
Started 129 [1] 126 [2]
Completed 118 [3] 114 [4]
Not Completed 11 12
Reason Not Completed
Lost to Follow-up             5             8
Missed 2-year visit             4             4
Death             2             0
[1]
129 participants were assigned to implant; 122 received implant
[2]
126 participants were assigned to systemic treatment; 121 received systemic therapy
[3]
118 participants completed the 2-year anniversary visit
[4]
114 participants completed the 2-year anniversary visit
Arm/Group Title Flucinolone Acetonide Intraocular Implant Standard Systemic Treatment Total
Hide Arm/Group Description Local therapy with fluocinolone acetonide 0.59 mg implant (Retisert; Bausch & Lomb Inc.) in each eye with uveitis of sufficient severity to justify treatment with systemic corticosteroids Systemic corticosteroid therapy with immunosuppression as indicated Total of all reporting groups
Overall Number of Baseline Participants 129 126 255
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 129 participants 126 participants 255 participants
46  (15) 47  (15) 46  (15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 126 participants 255 participants
Female
91
  70.5%
100
  79.4%
191
  74.9%
Male
38
  29.5%
26
  20.6%
64
  25.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 126 participants 255 participants
White 72 70 142
Hispanic 18 15 33
Black 35 31 66
Other 4 10 14
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 126 participants 255 participants
United States 109 104 213
Australia 5 6 11
United Kingdom 15 16 31
Bilateral uveitis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 126 participants 255 participants
116 108 224
Site of uveitis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 126 participants 255 participants
Intermediate 50 47 97
Posterior or Panuveitis 79 79 158
Associated systemic inflammatory disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 126 participants 255 participants
Yes 36 33 69
no 93 93 186
Visual acuity 20/40 or better  
Measure Type: Number
Unit of measure:  Eyes
Number Analyzed 129 participants 126 participants 255 participants
116 122 238
Active uveitis  
Measure Type: Number
Unit of measure:  Eyes
Number Analyzed 129 participants 126 participants 255 participants
192 181 373
Visual acuity 20/200 or worse  
Measure Type: Number
Unit of measure:  Eyes
Number Analyzed 129 participants 126 participants 255 participants
39 35 74
1.Primary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was an intention-to-treat analysis; analysis was conducted "as randomized". Data from the 255 randomized participants were used in the analytic model. 232 of the 255 completed the 2 year outcome visit.
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
A fluocinolone acetonide intravitreal implant (0.59 mg) was surgically placed by a study-certified surgeon was placed in each eligible eye. The first eye was implanted within 28 days of randomization and, if eligible, the second eye within the next 28 days. Prior to implant surgery, topical, periocular or systemic corticosteroids where used as needed to quiet the anterior chamber. Post-implant, systemic corticosteroids and immunosuppressive drugs were tapered and discontinued. If the second eye was not eligible for an implant initially but later became eligible, an implant was placed in the second eye at that time. The treatment algorithm included re-implantation upon reactivation and treatment per best medical judgment for failure to achieve inflammation control, treatment-limiting toxicity and systemic disease requiring systemic therapy.
Oral corticosteroids supplemented with immunosuppressive drugs if indicated were given according to published guidelines developed by an expert panel. For participants with active uveitis at baseline, 1 mg/kg/day up to 60 mg/day of prednisone was given until uveitis was controlled or 4 weeks had elapsed. When control was achieved, prednisone was tapered per study guidelines. Immunosuppressive drugs were added when uveitis was not initially controlled with prednisone alone, as corticosteroid-sparing agents when prednisone could not be tapered to 10 mg/day without reactivation of uveitis and for specific uveitis syndromes. Choice of immunosuppressant was made by the study ophthalmologist; immunosuppressant administration and monitoring for toxicity was conducted according to expert guidelines.
Overall Number of Participants Analyzed 129 126
Mean (Standard Error)
Unit of Measure: letters
6.0  (1.4) 3.2  (1.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments

Null hypothesis: There will be no difference in change in visual acuity between treatment groups.

Assuming 67% bilateral disease, between eye correlation of 0.4, SD of 16 letters' change over 2 years and two-sided type 1 error rate of .05, a sample size of 250 provided 91% power (assuming 10% crossover) to detect a treatment difference of 7.5 standard ETDRS letters' change in visual acuity from baseline to 24 months.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments unadjusted
Method Generalized estimating equations, linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.79
Confidence Interval (2-Sided) 95%
-1.16 to 6.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.03
Estimation Comments The 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).
2.Secondary Outcome
Title Macular Edema
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All eyes with uveitis were included in the analysis (245 eyes of the 129 participants randomized to implant therapy and 234 eyes of the 126 participants randomized to systemic therapy)..
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 129 126
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes with macular edema
245 234
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of eyes with uveitis
22
(14 to 30)
30
(21 to 40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.071
Comments unadjusted
Method GEE, logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of odds ratios
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.34 to 1.03
Estimation Comments For 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).
3.Secondary Outcome
Title Uveitis Activity
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All eyes with uveitis were included in the analysis (245 eyes of the 129 participants randomized to implant therapy and 234 eyes of the 126 participants randomized to systemic therapy).
Arm/Group Title Fluocinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy
Participants randomized to receive systemic therapy
Overall Number of Participants Analyzed 129 126
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes with uveitis
245 234
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of eyes with uveitis
12
(06 to 20)
29
(21 to 39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluocinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments unadjusted
Method GEE, logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of odds ratios
Estimated Value .29
Confidence Interval (2-Sided) 95%
.13 to .60
Estimation Comments For 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).
4.Secondary Outcome
Title Intraocular Pressure - Incident IOP Greater Than or Equal to 30 mm Hg
Hide Description [Not Specified]
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Eyes, not participants, were analyzed. Eyes with prevalent complications or missing data at enrollment were were excluded from the risk set.
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 129 126
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes with uveitis
234 229
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of eyes with uveitis at risk
32.8
(27.1 to 39.2)
6.3
(3.7 to 10.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments unadjusted
Method Cox proportional hazards w/ RE
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 6.08
Confidence Interval (2-Sided) 95%
3.32 to 11.15
Estimation Comments A 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.
5.Secondary Outcome
Title Intraocular Pressure - Incident IOP Greater Than or Equal to 24 mm Hg
Hide Description [Not Specified]
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Eyes, not participants, were analyzed. Eyes with prevalent complications or missing data at enrollment were were excluded from the risk set.
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 129 126
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes with uveitis
234 228
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of eyes with uveitis at risk
53.1
(46.9 to 59.7)
18.7
(14.2 to 24.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments unadjusted
Method Cox proportional hazards w/ RE
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 3.59
Confidence Interval (2-Sided) 95%
2.34 to 5.50
Estimation Comments A 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
6.Secondary Outcome
Title Intraocular Pressure - Incident IOP Elevation >= 10 mmHg Above Baseline
Hide Description [Not Specified]
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Eyes, not participants, were analyzed. Eyes with prevalent complications or missing data at enrollment were were excluded from the risk set.
Arm/Group Title Fluocinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy
Participants randomized to receive systemic therapy
Overall Number of Participants Analyzed 129 126
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes with uveitis
235 230
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of eyes with uveitis at risk
51.8
(45.5 to 58.3)
15.5
(11.4 to 20.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluocinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments unadjusted
Method Cox proportional hazards with RE
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 4.28
Confidence Interval (2-Sided) 95%
2.78 to 6.58
Estimation Comments A 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.
7.Secondary Outcome
Title Glaucoma - Incident
Hide Description Glaucoma was diagnosed by a glaucoma specialist through review of visual fields, clinical data, and fundus images.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Eyes, not participants, were analyzed. Eyes with prevalent complications or missing data at enrollment were were excluded from the risk set.
Arm/Group Title Fluocinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy
Participants randomized to receive systemic therapy
Overall Number of Participants Analyzed 129 126
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes with uveitis
212 202
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of eyes with uveitis at risk
16.5
(12.1 to 22.2)
4.0
(2.0 to 7.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluocinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments unadjusted
Method Cox proportional hazards w/ RE
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 4.19
Confidence Interval (2-Sided) 95%
1.82 to 9.63
Estimation Comments A 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.
8.Secondary Outcome
Title 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.
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Eyes, not participants, were analyzed. Eyes with prevalent complications or missing data at enrollment were were excluded from the risk set.
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy
Participants randomized to receive systemic therapy
Overall Number of Participants Analyzed 129 126
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
201 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of eyes with uveitis at risk
61.1
(54.3 to 67.8)
20.1
(15.1 to 26.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments unadjusted
Method Cox proportional hazards w/ RE
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 4.16
Confidence Interval (2-Sided) 95%
2.67 to 6.47
Estimation Comments A 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.
9.Secondary Outcome
Title Intraocular Pressure - IOP-lowering Surgery
Hide Description [Not Specified]
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Eyes, not participants, were analyzed. Eyes with prevalent complications or missing data at enrollment were were excluded from the risk set.
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 129 126
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes with uveitis
233 226
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of eyes with uveitis at risk
26.2
(21.0 to 32.4)
3.7
(1.9 to 7.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments unadjusted
Method Cox proportional hazards w/ RE
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 8.40
Confidence Interval (2-Sided) 95%
3.39 to 20.82
Estimation Comments A 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.
10.Secondary Outcome
Title Cataract - Incident Cataract
Hide Description [Not Specified]
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Eyes with uveitis, not participants, were analyzed. Eyes with prevalent complications or missing data at enrollment were were excluded from the risk set.
Arm/Group Title Fluocinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy
Participants randomized to receive systemic therapy
Overall Number of Participants Analyzed 129 126
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes with uveitis
54 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of eyes with uveitis at risk
90.7
(81.3 to 96.6)
44.9
(32.3 to 59.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluocinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments unadjusted
Method Cox proportional hazards w/ RE
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 4.12
Confidence Interval (2-Sided) 95%
2.21 to 7.67
Estimation Comments A 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.
11.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluocinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy
Participants randomized to receive systemic therapy
Overall Number of Participants Analyzed 129 126
Mean (Standard Error)
Unit of Measure: units on a scale (composite score)
11.44  (1.67) 6.80  (1.58)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluocinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments unadjusted
Method GEE, linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.64
Confidence Interval (2-Sided) 95%
0.14 to 9.15
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.30
Estimation Comments The 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).
12.Secondary Outcome
Title Change in SF-36 Mental Component Score From Baseline to 24 Months
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 129 126
Mean (Standard Error)
Unit of Measure: units on a scale
2.55  (1.11) -1.1  (1.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments unadjusted
Method GEE, linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.62
Confidence Interval (2-Sided) 95%
0.49 to 6.76
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.60
Estimation Comments The 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)
13.Secondary Outcome
Title Change in SF-36 Physical Component Score From Baseline to 24 Months
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 129 126
Mean (Standard Error)
Unit of Measure: units on a scale
1.15  (0.83) -1.8  (0.90)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments unadjusted
Method Generalized Estimating Equations
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.95
Confidence Interval (2-Sided) 95%
0.54 to 5.36
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.23
Estimation Comments The 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).
14.Secondary Outcome
Title Hyperlipidemia - Incident
Hide Description LDL greater than or equal to 160 mg/mL
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants at risk were included in the analysis
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 97 104
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants at risk
9.8
(5.2 to 18.0)
11.0
(6.3 to 19.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments unadjusted
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.39 to 2.15
Estimation Comments A 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.
15.Secondary Outcome
Title Hypertension Diagnosis Requiring Treatment
Hide Description [Not Specified]
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with prevalent complications or missing data at enrollment were excluded from the risk set.
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 88 88
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.6
(1.8 to 11.9)
10.5
(5.6 to 19.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments unadjusted
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.13 to 1.29
Estimation Comments A 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.
16.Secondary Outcome
Title Diabetes Mellitus
Hide Description [Not Specified]
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with prevalent complications or missing data at enrollment were excluded from the risk set.
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 105 114
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.0
(0.1 to 6.6)
3.6
(1.4 to 9.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flucinolone Acetonide Implant, Systemic Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.24
Comments unadjusted
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
0.03 to 2.44
Estimation Comments A 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.
17.Secondary Outcome
Title Mortality
Hide Description [Not Specified]
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description:
Participants randomized to receive implant therapy.
Participants randomized to receive systemic therapy.
Overall Number of Participants Analyzed 126 124
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.6
(0.4 to 6.3)
0 [1] 
(NA to NA)
[1]
no deaths reported in systemic group
Time Frame 2 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Flucinolone Acetonide Implant Systemic Therapy
Hide Arm/Group Description Participants randomized to receive implant therapy. Participants randomized to receive systemic therapy.
All-Cause Mortality
Flucinolone Acetonide Implant Systemic Therapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Flucinolone Acetonide Implant Systemic Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   75/129 (58.14%)      47/126 (37.30%)    
Cardiac disorders     
Pericardial drain placement *  0/129 (0.00%)  0 1/126 (0.79%)  1
Hypertension *  7/129 (5.43%)  12 3/126 (2.38%)  5
Cardiovascular *  2/129 (1.55%)  2 4/126 (3.17%)  5
Endocrine disorders     
Total thyroidectomy *  0/129 (0.00%)  0 1/126 (0.79%)  1
Eye disorders     
Endophthalmitis *  3/129 (2.33%)  3 0/126 (0.00%)  0
Glaucoma *  7/129 (5.43%)  11 1/126 (0.79%)  2
Hypotony *  4/129 (3.10%)  4 2/126 (1.59%)  2
Ocular Hypertension *  32/129 (24.81%)  54 5/126 (3.97%)  6
Retinal Detachment *  4/129 (3.10%)  5 1/126 (0.79%)  1
Vitreous Hemorrhage *  14/129 (10.85%)  15 4/126 (3.17%)  5
Bleb revision *  1/129 (0.78%)  1 0/126 (0.00%)  0
Complication of Kenalog injection *  1/129 (0.78%)  1 0/126 (0.00%)  0
Enucleation *  0/129 (0.00%)  0 1/126 (0.79%)  1
Hospitalization for cataract surgery *  0/129 (0.00%)  0 1/126 (0.79%)  2
Retisert wound dehiscence *  1/129 (0.78%)  1 0/126 (0.00%)  0
Choroidal neovascularization *  1/129 (0.78%)  1 0/126 (0.00%)  0
Hyphema *  1/129 (0.78%)  1 0/126 (0.00%)  0
Exposed suture *  1/129 (0.78%)  1 0/126 (0.00%)  0
Surgery to reposition shunt *  1/129 (0.78%)  1 0/126 (0.00%)  0
Iris bombe *  1/129 (0.78%)  1 0/126 (0.00%)  0
Exposed Ahmed valve *  1/129 (0.78%)  1 0/126 (0.00%)  0
Orbital cellulitis *  1/129 (0.78%)  1 0/126 (0.00%)  0
Revision of Ahmed valve *  1/129 (0.78%)  1 0/126 (0.00%)  0
Abnormal ERG *  0/120 (0.00%)  0 1/126 (0.79%)  1
Gastrointestinal disorders     
Diarrhea, dehydration *  0/129 (0.00%)  0 1/126 (0.79%)  1
Ileostomy takedown *  0/129 (0.00%)  0 1/126 (0.79%)  1
Perforated viscus lung cancer *  0/129 (0.00%)  0 1/126 (0.79%)  1
Exacerbation of intestinal fissure *  0/129 (0.00%)  0 1/126 (0.79%)  1
Gastrointestinal *  1/129 (0.78%)  3 2/126 (1.59%)  2
General disorders     
Prolonged hospitalization stay due to reaction *  1/120 (0.83%)  1 0/126 (0.00%)  0
Abdominal pain *  0/129 (0.00%)  0 1/126 (0.79%)  1
Flu-like reaction to Avonex *  0/129 (0.00%)  0 1/126 (0.79%)  1
Hospitalization *  0/129 (0.00%)  0 1/126 (0.79%)  1
Headache due to hypertension *  0/129 (0.00%)  0 1/126 (0.79%)  1
Hepatobiliary disorders     
Gall bladder surgery *  0/129 (0.00%)  0 2/126 (1.59%)  2
Abnormal laboratory value *  4/129 (3.10%)  5 1/126 (0.79%)  1
Immune system disorders     
Neuro Bechet's disease *  0/129 (0.00%)  0 1/126 (0.79%)  1
Infections and infestations     
Infection *  6/129 (4.65%)  9 5/126 (3.97%)  5
Injury, poisoning and procedural complications     
Torn medial meniscus *  1/129 (0.78%)  1 0/126 (0.00%)  0
Fracture *  1/129 (0.78%)  1 6/126 (4.76%)  6
Investigations     
Chest pain *  1/129 (0.78%)  2 3/126 (2.38%)  3
Musculoskeletal and connective tissue disorders     
Hip replacement *  2/129 (1.55%)  2 0/126 (0.00%)  0
Shoulder surgery *  0/129 (0.00%)  0 1/126 (0.79%)  1
Arthrosis due to aseptic necrosis *  0/129 (0.00%)  0 1/126 (0.79%)  1
Dislocation of hip *  0/129 (0.00%)  0 1/126 (0.79%)  1
Ankylosing spondylitis *  1/129 (0.78%)  1 0/126 (0.00%)  0
Hip pain *  0/129 (0.00%)  0 1/126 (0.79%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hospitalization for post-surgical observation of pharyngeal papilloma biopsy *  0/129 (0.00%)  0 1/126 (0.79%)  1
Cancer *  1/129 (0.78%)  1 3/126 (2.38%)  3
Nervous system disorders     
Anterior cervical dissection, fusion *  1/129 (0.78%)  1 0/126 (0.00%)  0
Psychiatric disorders     
Hospitalization for observation while on prednisone *  1/129 (0.78%)  1 0/126 (0.00%)  0
Psychotic episode *  0/129 (0.00%)  0 1/126 (0.79%)  1
Renal and urinary disorders     
Kidney stones *  1/129 (0.78%)  1 0/126 (0.00%)  0
Hemmorhagic cystitis *  0/129 (0.00%)  0 1/126 (0.79%)  1
Hydronephrosis *  1/129 (0.78%)  1 0/126 (0.00%)  0
Reproductive system and breast disorders     
Hysterectomy *  1/129 (0.78%)  1 1/126 (0.79%)  1
Precancerous cells right breast *  1/129 (0.78%)  1 0/126 (0.00%)  0
Cervical dysplasia *  1/129 (0.78%)  1 0/126 (0.00%)  0
Miscarriage *  1/129 (0.78%)  1 3/126 (2.38%)  3
Skin and subcutaneous tissue disorders     
Non-melanoma skin cancer *  1/129 (0.78%)  1 3/126 (2.38%)  7
Vascular disorders     
Thrombosis *  4/129 (3.10%)  4 2/126 (1.59%)  2
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Flucinolone Acetonide Implant Systemic Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   113/129 (87.60%)      113/126 (89.68%)    
Cardiac disorders     
Hypertension (systolic)   27/129 (20.93%)  38 32/126 (25.40%)  62
Hypertension (diastolic)   24/129 (18.60%)  39 30/126 (23.81%)  47
Eye disorders     
Ocular hypertension   78/129 (60.47%)  246 29/126 (23.02%)  67
Glaucoma   10/129 (7.75%)  13 2/126 (1.59%)  5
Hypotony   26/129 (20.16%)  46 10/126 (7.94%)  28
Cataract   40/129 (31.01%)  65 13/126 (10.32%)  15
Vitreous hemorrhage   13/129 (10.08%)  15 2/126 (1.59%)  2
Gastrointestinal disorders     
Nausea *  5/129 (3.88%)  7 20/126 (15.87%)  24
Vomiting *  5/129 (3.88%)  5 11/126 (8.73%)  15
Diarrhea *  2/129 (1.55%)  2 12/126 (9.52%)  16
General disorders     
Headache *  25/129 (19.38%)  36 19/126 (15.08%)  21
Fatigue *  6/129 (4.65%)  7 11/126 (8.73%)  15
Infection *  52/129 (40.31%)  116 67/126 (53.17%)  178
Hepatobiliary disorders     
SGOT (AST) or SGPT (ALT)   5/129 (3.88%)  9 8/126 (6.35%)  13
Immune system disorders     
Allergic reaction *  10/129 (7.75%)  16 9/126 (7.14%)  11
Metabolism and nutrition disorders     
Hyperglycemia (fasting)   4/129 (3.10%)  4 10/126 (7.94%)  16
Hyperglycemia (casual)   6/129 (4.65%)  8 10/126 (7.94%)  16
Hypoglycemia   7/129 (5.43%)  8 6/126 (4.76%)  6
Triglyceride (high)   10/129 (7.75%)  12 10/126 (7.94%)  12
Musculoskeletal and connective tissue disorders     
Osteoporosis   12/129 (9.30%)  12 10/126 (7.94%)  10
Psychiatric disorders     
Mood *  4/129 (3.10%)  4 11/126 (8.73%)  12
Renal and urinary disorders     
BUN   8/129 (6.20%)  8 10/126 (7.94%)  16
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John H. Kempen, MD, PhD, MUST Trial Vice-Chairman
Organization: Center for Presventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania
Phone: 215-615-1500
EMail: john.kempen@uphs.upenn.edu
Publications of Results:
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):
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Responsible Party: JHSPH Center for Clinical Trials
ClinicalTrials.gov Identifier: NCT00132691    
Obsolete Identifiers: NCT00269698
Other Study ID Numbers: NEI-106
U10EY014660 ( U.S. NIH Grant/Contract )
1U10EY014660-2
ISRCTN15396562
First Submitted: August 19, 2005
First Posted: August 22, 2005
Results First Submitted: May 14, 2012
Results First Posted: July 30, 2012
Last Update Posted: November 25, 2016