Diabetic Macular Edema
Conditions
Keywords
Diabetic macular edema, Ozurdex
Brief summary
Multicentre randomized controlled trial to evaluate whether 5 monthly fixed dosing of 700 µg Dexamethasone Posterior Segment Drug Delivery System (Ozurdex) is as efficacious as Optical coherence tomography (OCT)-guided PRN dosing in patients with refractory diabetic macular edema.
Interventions
DEVICEOzurdex
Dexamethasone implant (Ozurdex)
Sponsors
The Royal Wolverhampton Hospitals NHS Trust
Frimley Park Hospital NHS Trust
Brighton and Sussex University Hospitals NHS Trust
University Hospitals Bristol and Weston NHS Foundation Trust
Moorfields Eye Hospital NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects of either sex aged 18 years or over 2. Diagnosis of diabetes mellitus (type 1 or type 2). 3. Best corrected visual acuity in the study eye between ≥34 and ≤73 ETDRS letters at 1m at baseline attributable to diabetic macular edema (DME) 4. On clinical exam at baseline in the study eye, retinal thickening due to diabetic macular oedema involving the centre of the macula and OCT central subfield \> 300 microns despite previous therapy. 5. Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs. 6. Ability to return for study visits 7. Visual acuity in fellow eye ≥ 2/60 8. Ability to give informed consent throughout the duration of the study Main
Exclusion criteria
1. Macular ischaemia 2. Macular oedema is considered to be due to a cause other than diabetic macular oedema. 3. Co-existent ocular disease 4. An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular oedema or alter visual acuity during the course of the study. 5. A substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Difference Between Arms in the Change From Baseline in Best Corrected Visual Acuity at 12 Months | Baseline and 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Arms in Change From Baseline Composite Scores of the National Eye Institute Visual Function Questionnaire (VFQ-25). | Baseline and 12 months | NEI VFQ 25 is a questionnaire intended to measure visual function and quality of life. It has 25 questions. The original response of each item are coded as per the NEI VFQ scoring system ranging from 0 (lowest) to 100 (highest). Composite score = (Score for each item with a non-missing answer) / Total number of items with non-missing answers 100 = Best, 0 = Worst possible score |
| Difference Between Arms in Change in Central Subfield Thickness. | Baseline and 12 months | Central subfield thickness is defined as the average thickness in the central 1mm diameter circle of the ETDRS grid and is measured in microns |
| Proportion of Patients With Ocular and Systemic Serious Adverse Events | 12 months | — |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ozurdex PRN Dosing Ozurdex PRN dosing versus Ozurdex fixed dosing
Ozurdex: Dexamethasone implant (Ozurdex) | 50 |
| Ozurdex Fixed Dosing Ozurdex: Dexamethasone implant (Ozurdex) | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Ozurdex Fixed Dosing | Ozurdex PRN Dosing | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 25 Participants | 30 Participants | 55 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 20 Participants | 45 Participants |
| Age, Continuous | 63.8 years STANDARD_DEVIATION 11.1 | 65.4 years STANDARD_DEVIATION 9.8 | 64.6 years STANDARD_DEVIATION 10.5 |
| Gender Female | 10 Participants | 16 Participants | 26 Participants |
| Gender Male | 40 Participants | 34 Participants | 74 Participants |
| Region of Enrollment United Kingdom | 50 participants | 50 participants | 100 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 50 | 8 / 50 |
| serious Total, serious adverse events | 10 / 50 | 9 / 50 |
Outcome results
Primary
The Difference Between Arms in the Change From Baseline in Best Corrected Visual Acuity at 12 Months
Time frame: Baseline and 12 months
Population: Intention to treat analysis (available case)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ozurdex PRN Dosing | The Difference Between Arms in the Change From Baseline in Best Corrected Visual Acuity at 12 Months | 0 ETDRS letters | Standard Deviation 13 |
| Ozurdex Fixed Dosing | The Difference Between Arms in the Change From Baseline in Best Corrected Visual Acuity at 12 Months | 0.53 ETDRS letters | Standard Deviation 16.1 |
Secondary
Difference Between Arms in Change From Baseline Composite Scores of the National Eye Institute Visual Function Questionnaire (VFQ-25).
NEI VFQ 25 is a questionnaire intended to measure visual function and quality of life. It has 25 questions. The original response of each item are coded as per the NEI VFQ scoring system ranging from 0 (lowest) to 100 (highest). Composite score = (Score for each item with a non-missing answer) / Total number of items with non-missing answers 100 = Best, 0 = Worst possible score
Time frame: Baseline and 12 months
Population: Though 48 patients completed the trial in the PRN arm, one patient did not complete the questionnaire completely, making it invalid for analysis. Hence the PRN arm number for this outcome was 47
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ozurdex PRN Dosing | Difference Between Arms in Change From Baseline Composite Scores of the National Eye Institute Visual Function Questionnaire (VFQ-25). | -0.45 units on a scale | Standard Deviation 12.2 |
| Ozurdex Fixed Dosing | Difference Between Arms in Change From Baseline Composite Scores of the National Eye Institute Visual Function Questionnaire (VFQ-25). | 3.02 units on a scale | Standard Deviation 15.4 |
Secondary
Difference Between Arms in Change in Central Subfield Thickness.
Central subfield thickness is defined as the average thickness in the central 1mm diameter circle of the ETDRS grid and is measured in microns
Time frame: Baseline and 12 months
Population: Few patients in both groups developed cataract. Due to the dense cataract, it was not possible to obtain the macular scans. Hence the discrepancy between the population who completed the study and the number for whom the OCT was obtained at exit visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ozurdex PRN Dosing | Difference Between Arms in Change in Central Subfield Thickness. | -90.1 microns | Standard Deviation 96.2 |
| Ozurdex Fixed Dosing | Difference Between Arms in Change in Central Subfield Thickness. | -179.9 microns | Standard Deviation 172.4 |
Secondary
Proportion of Patients With Ocular and Systemic Serious Adverse Events
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozurdex PRN Dosing | Proportion of Patients With Ocular and Systemic Serious Adverse Events | 10 participants |
| Ozurdex Fixed Dosing | Proportion of Patients With Ocular and Systemic Serious Adverse Events | 9 participants |