Clinical trial NCT04619303: Intravitreal Dexamethasone vs Bevacizumab in Aboriginal People With DMO
Official title: A Randomized Clinical Trial of Intravitreal dexamethasOne Versus Bevacizumab in Aboriginal and Torres Strait Islander patientS With Diabetic Macular Oedema (The OASIS Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Macular Edema
Diabetic Retinopathy
Keywords: Diabetic macular edema
Aboriginal
Australian
Lead sponsor: Lions Eye Institute, Perth, Western Australia
Sponsor class: OTHER
Collaborators: name: Lions Outback Vision
name: Allergan
First posted: 2020-11-06
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

* Self-identifying as Aboriginal Australian or Torres Strait Islander
* Adults aged 18 years and over
* Diagnosis of DM (type 1 or type 2)
* BCVA of at best 0.2 LogMAR (20/32) 6/9 in the study eye
* Pseudophakic, or phakic with significant lens opacity and scheduled to undergo cataract surgery at the time of enrolment
* Presence of any grade of DR with centre-involving DMO, as defined by clinical examination and OCT scan findings

  * Active DMO: Centre-involving/threatening DMO, as defined by clinical examination and OCT scan findings.
  * At risk of DMO: Patients scheduled for cataract surgery with non-centre involving DMO who are assessed as being at risk of post-operative centre-involving DMO based on clinical examination, OCT scan findings, and Investigator discretion.

Exclusion criteria:

* Intervention: Previous treatment in the study eye including at the time of the first trial treatment with:

  * IVT anti-VEGF injections within the last six weeks;
  * Macular laser treatment within the last four months;
  * IVT triamcinolone or triescence within the last six months; at the time of the first trial treatment.
* History of open-angle glaucoma or steroid-induced IOP elevation that required IOP-lowering treatment or, IOP ≥25 (Goldmann applanation) on two consecutive clinic visits.
* Eyes with concurrent ocular pathology other than DMO, or a cataract-causing visual loss, including macular ischaemia as determined by clinical examination and FFA imaging.
* Women who are breastfeeding, confirmed as pregnant or planning on becoming pregnant in the next 6-12 months.
* Participants for whom Ozurdex or Avastin treatment are contraindicated as per product information:

  * Active or suspected ocular/periocular infections, including most viral diseases of the cornea and conjunctiva, active epithelia herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.
  * Aphakic eyes with rupture of the posterior lens capsule.
  * Eyes with an anterior chamber intraocular lens and rupture of the posterior lens capsule.
  * Known angina, myocardial infarction, TIA or CVA in the last three months.
  * Known hypersensitivity to any components of these products.

Primary outcomes:
measure: Difference in best corrected visual acuity change between treatment arms
timeFrame: 12 months
Secondary outcomes:
measure: Best corrected visual acuity loss or gain
timeFrame: 12 months
measure: Change in central macular thickness
timeFrame: 12 months
measure: Number of injections
timeFrame: 12 months
measure: Appointments attended
timeFrame: 12 months
measure: Intraocular pressure change
timeFrame: 12 months
measure: Intraocular pressure elevation
timeFrame: 12 months
measure: Intraocular pressure elevation requiring treatment
timeFrame: 12 months
measure: Adverse Events
timeFrame: 12 months
Other outcomes:
Locations:
city: Broome
country: Australia
facility: Broome Regional Aboriginal Medical Service
state: Western Australia
city: Derby
country: Australia
facility: Derby Hospital
state: Western Australia
city: Fitzroy Crossing
country: Australia
facility: Fitzroy Crossing Hospital
state: Western Australia
city: Halls Creek
country: Australia
facility: Halls Creek Health Service
state: Western Australia
city: Kalgoorlie
country: Australia
facility: Bega Garnbirringu Health Service
state: Western Australia
city: Karratha
country: Australia
facility: Nickol Bay Hospital
state: Western Australia
city: Kununurra
country: Australia
facility: Ord Valley Aboriginal Health Service
state: Western Australia
city: Laverton
country: Australia
facility: Laverton Hospital
state: Western Australia
city: Perth
country: Australia
facility: Derbarl Yerrigan Health Service Inc.
state: Western Australia
city: Perth
country: Australia
facility: Lions Eye Institute Nedlands
state: Western Australia
city: Perth
country: Australia
facility: Lions Eye Institute Midland
state: Western Australia
city: Roebourne
country: Australia
facility: Mawarnkarra Health Service
state: Western Australia
city: South Hedland
country: Australia
facility: Wirraka Maya Health Service Aboriginal Corporation
state: Western Australia
Study officials:
affiliation: Lions Eye Institute
name: Angus Turner, FRANZCO
role: STUDY_DIRECTOR
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