Open Label Extension of a Clinical Trial of Intravitreal Triamcinolone for Diabetic Macular Oedema-TDMX Study

Study Overview
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Brief Summary
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This open label extension will treat all the eyes of study participants with active study medication (intravitreal triamcinolone) as well as standard laser treatment where appropriate. The specific aims will be to test the following hypotheses: That intravitreal triamcinolone for diabetic macular oedema that persists or recurs after laser treatment remains efficacious over five years That intravitreal triamcinolone for diabetic macular oedema that persists or recurs after laser treatment retains a manageable and acceptable safety profile over five years

Detailed Description
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A 25 fold increase in the risk of going blind on diagnosis of diabetes is one of the most daunting threats that patients face. People using insulin are particularly challenged because they are unable accurately to draw up their dose of drug. Most cases of vision impairment in diabetes are due to macular oedema that persists or recurs after laser treatment. There are now a number of uncontrolled, anecdotal reports that intravitreal triamcinolone (IVTA) is highly effective for the treatment of diabetic macular edema which is refractory to conventional laser treatment. We commenced the first placebo-controlled, double masked clinical trial of IVTA for refractory macular oedema in 2002. The 3 month results from this study provide the first scientific proof of principle that IVTA reduces macular thickness and improves vision. The two year results will be available in March 2005, but confidential interim analysis of efficacy data in September 2004 suggested that the beneficial effect of triamcinolone treatment persisted. Thus it appears that treatment with IVTA may be the most significant development for the prevention of blindness in people with diabetes since the introduction of laser treatment. It would also be a highly cost-effective intervention that could be administered by general ophthalmologists. The treatment cannot be recommended for routine use, however, until its long term efficacy and safety have been established. Since we already have a well studied group of patients who have received treatment for 2 years, we are in a unique position to extend the study in order to provide the long-term (5-year) safety and efficacy data that does not appear to be forthcoming from any other source. The completion of this study will have a direct and immediate effect on the risk of blindness in people with diabetes by allowing doctors to predict more accurately the long term effects of this promising new treatment.

Official Title
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An Open Label Extension of the Phase II/III Clinical Trial of Intravitreal Triamcinolone on the Effects and Safety of Clinically Significant Diabetic Macular Oedema That Persists After Laser Treatment

Conditions
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Diabetic Macular Oedema

Intervention / Treatment
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* Drug: Triamcinolone acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in the study will be offered to all patients at the conclusion of the TDMO study. Currently we are still following 64 of the 69 (93%) eyes that were initially entered into the study that had reduced vision from diabetic macular oedema at baseline. Exclusion Criteria: Uncontrolled glaucoma Loss of vision due to other causes (e.g. age related macular degeneration, myopic macular degeneration) known allergies to triamcinolone acetate, patient is already receiving systemic steroid treatment, intercurrent severe disease such as septicemia, any condition which would affect follow-up or photographic documentation (e.g. geographical, psycho-social, media opacities)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Triamcinolone acetate|When indicated, intravitreal triamcinolone (0.1 ml of Kenacort 40© [40mg/ml triamcinolone acetonide, Bristol-Myers Squibb pharmaceuticals, Australia]) was injected into the vitreous under sterile conditions in a minor procedures area.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase of ≥5 letters at the 5-year study visit on a LogMAR chart compared with (a) the initial baseline level and (b) the level at the 2-year study visit. | Changes from Baseline to 5 years: Improvement of ≥5 letters after 5 years was found in 14/33 (42%) eyes initially treated with triamcinolone compared with 11/34 (32%) eyes initially treated with placebo (zGEE=0.81, P=0.4). Changes from 2 to 5 years (open-label extension):Improvement of ≥5 letters of best-corrected visual acuity was found in 8/29 (28%) eyes initial-triamcinolone compared with 7/28 (25%) initial-placebo eyes (zGEE=0.20, P=0.8). | 3 year extension, total 5 years study from baseline | 
| Incidence of moderate or severe adverse events over the 3 years of the open-label extension | The incidence of cataract surgery declined in the third year: 5/11 (45%) eyes from the initial-triamcinolone group that were phakic at the beginning of the 3rd year required cataract surgery. | 3 year extension study, total 5 year study from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in macular thickness by OCT | Changes from Baseline to 5 years: Foveal thickness had decreased by 30µm (95% confidence interval, -47 to 107µm) less in the initial-triamcinolone group than in the initial-placebo group at 5 years (zGEE=0.76, P=0.45). Changes from 2 to 5 years (open-label extension):Foveal thickness had actually increased slightly on average in the initial-triamcinolone group, but decreased in initial-placebo eyes. Overall it had decreased by 70µm (95% confidence interval, -1 to 140µm) more in the placebo group than in the treatment group between 2 and 5 years (zGEE=1.93, P=0.05). | 3 year extension, total 5 year study from the baseline | 
| Any change in visual acuity | Loss of ten or more letters was found in 6/33 (18%) initial-triamcinolone eyes compared with 8/34 (24%) initial-placebo eyes. | 3 year extension, total 5 year study from the baseline | 
| Number of laser treatments required. | During the third to fifth years of the study, a similar proportion of eyes from the 2 groups had macular edema that warranted laser treatment: initial-triamcinolone, 5/29 (17%); initial-placebo, 6/28 (21%). | 3 year extension study, total 5 year study from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic macular oedema, Triamcinolone acetate, Intravitreal injection, Clinical trial, Laser treatment