Intravitreal Dexamethasone vs Bevacizumab in Aboriginal People With DMO

NCT ID: NCT04619303

Last Updated: 2020-11-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-07

Study Completion Date

2020-02-14

Brief Summary

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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

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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.

Conditions

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Diabetic Macular Edema Diabetic Retinopathy

Keywords

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Diabetic macular edema Aboriginal Australian

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Dexamethasone 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.

Group Type EXPERIMENTAL

Dexamethasone intravitreal implant

Intervention Type DRUG

Intravitreal injection of 0.7mg dexamethasone implant

Bevacizumab

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.

Group Type ACTIVE_COMPARATOR

Bevacizumab Injectable Product

Intervention Type DRUG

Invtravitreal injection of 1.25mg/0.05mL bevacizumab

Interventions

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Dexamethasone intravitreal implant

Intravitreal injection of 0.7mg dexamethasone implant

Intervention Type DRUG

Bevacizumab Injectable Product

Invtravitreal injection of 1.25mg/0.05mL bevacizumab

Intervention Type DRUG

Other Intervention Names

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Ozurdex DEX-implant Avastin

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lions Outback Vision

UNKNOWN

Sponsor Role collaborator

Allergan

INDUSTRY

Sponsor Role collaborator

Lions Eye Institute, Perth, Western Australia

OTHER

Sponsor Role lead

Responsible Party

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A/Prof. Hessom Razavi

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Angus Turner, FRANZCO

Role: STUDY_DIRECTOR

Lions Eye Institute

Locations

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Broome Regional Aboriginal Medical Service

Broome, Western Australia, Australia

Site Status

Derby Hospital

Derby, Western Australia, Australia

Site Status

Fitzroy Crossing Hospital

Fitzroy Crossing, Western Australia, Australia

Site Status

Halls Creek Health Service

Halls Creek, Western Australia, Australia

Site Status

Bega Garnbirringu Health Service

Kalgoorlie-Boulder, Western Australia, Australia

Site Status

Nickol Bay Hospital

Karratha, Western Australia, Australia

Site Status

Ord Valley Aboriginal Health Service

Kununurra, Western Australia, Australia

Site Status

Laverton Hospital

Laverton, Western Australia, Australia

Site Status

Derbarl Yerrigan Health Service Inc.

Perth, Western Australia, Australia

Site Status

Lions Eye Institute Nedlands

Perth, Western Australia, Australia

Site Status

Lions Eye Institute Midland

Perth, Western Australia, Australia

Site Status

Mawarnkarra Health Service

Roebourne, Western Australia, Australia

Site Status

Wirraka Maya Health Service Aboriginal Corporation

South Hedland, Western Australia, Australia

Site Status

Countries

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Australia

References

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Chang-Lin JE, Attar M, Acheampong AA, Robinson MR, Whitcup SM, Kuppermann BD, Welty D. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant. Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):80-6. doi: 10.1167/iovs.10-5285.

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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://www.abs.gov.au/ausstats/[email protected]/Lookup/4820.0.55.001Media+Release12007-08

Australian Bureau of Statistics. Diabetes in Australia: A Snapshot, 2007-08. Cat. no. 4820.0.

Other Identifiers

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OASIS

Identifier Type: -

Identifier Source: org_study_id