Intravitreal Dexamethasone vs Bevacizumab in Aboriginal People With DMO
- Conditions
- Diabetic Macular EdemaDiabetic Retinopathy
- Interventions
- Registration Number
- NCT04619303
- Lead Sponsor
- Lions Eye Institute, Perth, Western Australia
- Brief Summary
DMO is the most common cause of visual loss in people with diabetes. Regular injections of bevacizumab (Avastin) given as frequently as every month remain the current standard of care for centre-involving DMO; however, this regimen is impractical for many Aboriginal patients. Using Ozurdex implants every 3-6 months could be as effective as the currently used Avastin injections. In order to address this real-world problem, this study seeks to investigate whether it is possible to safely use a long-acting steroid preparation such as the dexamethasone IVT implant (Ozurdex) to manage DMO in Aboriginal patients living in Western Australia.
- Detailed Description
The prevalence of self-reported DM in Aboriginal Australians is reported to be as high as 38%. Despite gradual improvements in underlying social determinants of health, the high morbidity and mortality attributed to DM in Aboriginal populations indicates significant ongoing issues with adherence to screening and treatment regimens. The greater prevalence of DM in the Aboriginal Australian population would be expected to account (at least in part) for the observed complication rates, including DR.
DMO is characterised by swelling of the central retina. The hypoxic retinal conditions in diabetic individuals result in structural changes in the vessel walls and a functional impairment of the blood-retinal barrier. The resultant increase in vascular permeability causes retinal oedema, and loss of central vision ensues when oedema involves the macula. Treatment is aimed at reducing visual loss by targeting factors involved in the activated hypoxia pathway, or with laser targeting dysfunctional blood vessels to limit leakage. Laser was the first treatment shown to effectively reduce DMO and improve vision; however, it cannot be applied to the very centre of the macula. More recently, DMO has been shown to respond to intraocular injections with anti-VEGF agents (bevacizumab, ranibizumab, and aflibercept), reducing reliance on laser treatments.
Corticosteroids are anti-inflammatory agents with anti-VEGF and anti-proliferative effects. Unfortunately, the increased rates of cataract and elevated IOP are the main adverse effects of the IVT corticosteroid treatments, including triamcinolone, making this a less-appealing option than anti-VEGF agents. However, their efficacy has been demonstrated in a subgroup of pseudophakic patients with DMO, where triamcinolone plus laser treatment was shown to be superior to laser treatment alone, and equivalent to ranibizumab (alone or with laser treatment). First-line treatment with triamcinolone is also the most cost-effective option for pseudophakic patients. Thus, IVT triamcinolone is considered one of the effective adjunct modalities for the treatment of DMO and has emerged as an alternative therapy to anti-VEGF agents for persistent or refractory DMO.
Ozurdex (Allergan, Irvine, CA, United States) is a unique biodegradable dexamethasone IVT implant. This slow-release preparation of dexamethasone (a highly potent steroid with a short half-life) has greater long-term efficacy than conventional forms of IVT triamcinolone, with the IVT concentration peaking within 3 months and sustained for up to 6 months post injection. This translates clinically to less frequent injections than conventional treatment with monthly IVT triamcinolone. The geography and population being studied in this trial create some unique challenges, which demand a more flexible study protocol. Longer-acting IVT agents such as Ozurdex have the potential to significantly improve DMO-associated visual morbidity with greater feasibility when used for Aboriginal patients with or at risk of DMO.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 59
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dexamethasone Implant Dexamethasone intravitreal implant Receive 0.7mg dexamethasone implant (Ozurdex) at baseline visit. Monthly review with repeat administration of intravitreal treatment every three months for DMO and laser as clinically indicated. Bevacizumab Bevacizumab Injectable Product Receive 1.25mg/0.05ml bevacizumab (Avastin) at baseline visit. Monthly review with repeat administration of intravitreal treatment every one month for DMO and laser as clinically indicated.
- Primary Outcome Measures
Name Time Method Difference in best corrected visual acuity change between treatment arms 12 months The primary outcome measure will be the difference in the BCVA change from baseline to 12 months between treatment arms, with a non-inferiority margin of 0.1 LogMAR (equivalent to one line of Snellen visual acuity). The BCVA will be measured for all study participants at each clinic visit.
- Secondary Outcome Measures
Name Time Method Best corrected visual acuity loss or gain 12 months The proportion of participants with a BCVA loss or gain of \<0.3 LogMAR (termed 'stable BCVA'), a BCVA loss of ≥0.3 LogMAR ('decline in BCVA'), or a BCVA gain of ≥0.3 LogMAR ('gain in BCVA').
Change in central macular thickness 12 months Change in the CMT from baseline to 12 months as measured by OCT.
Number of injections 12 months Number of IVT injections given per participant.
Appointments attended 12 months Number of appointments attended per participant.
Intraocular pressure change 12 months The change in the mean IOP.
Intraocular pressure elevation 12 months The number of participants with one or more occasions of IOP elevation \>28 mmHg.
Intraocular pressure elevation requiring treatment 12 months IOP elevation requiring medical, laser or surgical treatment.
Adverse Events 12 months Adverse events (AEs), serious adverse events (SAEs) and serious adverse reactions (SARs) coded according to the National Medical Research Council (2016) safety monitoring and reporting in clinical trials definitions.
Trial Locations
- Locations (13)
Derby Hospital
🇦🇺Derby, Western Australia, Australia
Ord Valley Aboriginal Health Service
🇦🇺Kununurra, Western Australia, Australia
Broome Regional Aboriginal Medical Service
🇦🇺Broome, Western Australia, Australia
Nickol Bay Hospital
🇦🇺Karratha, Western Australia, Australia
Mawarnkarra Health Service
🇦🇺Roebourne, Western Australia, Australia
Bega Garnbirringu Health Service
🇦🇺Kalgoorlie, Western Australia, Australia
Fitzroy Crossing Hospital
🇦🇺Fitzroy Crossing, Western Australia, Australia
Laverton Hospital
🇦🇺Laverton, Western Australia, Australia
Wirraka Maya Health Service Aboriginal Corporation
🇦🇺South Hedland, Western Australia, Australia
Lions Eye Institute Nedlands
🇦🇺Perth, Western Australia, Australia
Lions Eye Institute Midland
🇦🇺Perth, Western Australia, Australia
Derbarl Yerrigan Health Service Inc.
🇦🇺Perth, Western Australia, Australia
Halls Creek Health Service
🇦🇺Halls Creek, Western Australia, Australia