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Intravitreal Dexamethasone vs Bevacizumab in Aboriginal People With DMO (OASIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04619303
Recruitment Status : Completed
First Posted : November 6, 2020
Last Update Posted : November 9, 2020
Sponsor:
Collaborators:
Lions Outback Vision
Allergan
Information provided by (Responsible Party):
A/Prof. Hessom Razavi, Lions Eye Institute, Perth, Western Australia

Study Description
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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.

Condition or disease Intervention/treatment Phase
Diabetic Macular Edema Diabetic Retinopathy Drug: Dexamethasone intravitreal implant Drug: Bevacizumab Injectable Product Phase 4

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 7, 2017
Actual Primary Completion Date : February 14, 2020
Actual Study Completion Date : February 14, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: Dexamethasone intravitreal implant
Intravitreal injection of 0.7mg dexamethasone implant
Other Names:
  • Ozurdex
  • DEX-implant
Active Comparator: 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.
 Drug: Bevacizumab Injectable Product
Invtravitreal injection of 1.25mg/0.05mL bevacizumab
Other Name: Avastin


Outcome Measures
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Primary Outcome Measures :
  1. Difference in best corrected visual acuity change between treatment arms [ Time Frame: 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 :
  1. Best corrected visual acuity loss or gain [ Time Frame: 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').

  2. Change in central macular thickness [ Time Frame: 12 months ]
    Change in the CMT from baseline to 12 months as measured by OCT.

  3. Number of injections [ Time Frame: 12 months ]
    Number of IVT injections given per participant.

  4. Appointments attended [ Time Frame: 12 months ]
    Number of appointments attended per participant.

  5. Intraocular pressure change [ Time Frame: 12 months ]
    The change in the mean IOP.

  6. Intraocular pressure elevation [ Time Frame: 12 months ]
    The number of participants with one or more occasions of IOP elevation >28 mmHg.

  7. Intraocular pressure elevation requiring treatment [ Time Frame: 12 months ]
    IOP elevation requiring medical, laser or surgical treatment.

  8. Adverse Events [ Time Frame: 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04619303


Locations
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Australia, Western Australia
Broome Regional Aboriginal Medical Service
Broome, Western Australia, Australia, 6725
Derby Hospital
Derby, Western Australia, Australia, 6728
Fitzroy Crossing Hospital
Fitzroy Crossing, Western Australia, Australia, 6728
Halls Creek Health Service
Halls Creek, Western Australia, Australia, 6770
Bega Garnbirringu Health Service
Kalgoorlie, Western Australia, Australia, 6430
Nickol Bay Hospital
Karratha, Western Australia, Australia, 6714
Ord Valley Aboriginal Health Service
Kununurra, Western Australia, Australia, 6743
Laverton Hospital
Laverton, Western Australia, Australia, 6440
Derbarl Yerrigan Health Service Inc.
Perth, Western Australia, Australia, 6004
Lions Eye Institute Nedlands
Perth, Western Australia, Australia, 6009
Lions Eye Institute Midland
Perth, Western Australia, Australia, 6056
Mawarnkarra Health Service
Roebourne, Western Australia, Australia, 6718
Wirraka Maya Health Service Aboriginal Corporation
South Hedland, Western Australia, Australia, 6722
Sponsors and Collaborators
Lions Eye Institute, Perth, Western Australia
Lions Outback Vision
Allergan
Investigators
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Study Director: Angus Turner, FRANZCO Lions Eye Institute
  Study Documents (Full-Text)

Documents provided by A/Prof. Hessom Razavi, Lions Eye Institute, Perth, Western Australia:
Study Protocol and Statistical Analysis Plan  [PDF] January 6, 2017

More Information
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Additional Information:

Publications:

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Responsible Party: A/Prof. Hessom Razavi, Associate Professor, Lions Eye Institute, Perth, Western Australia
ClinicalTrials.gov Identifier: NCT04619303    
Other Study ID Numbers: OASIS
First Posted: November 6, 2020    Key Record Dates
Last Update Posted: November 9, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data as well as visit data with primary and secondary outcome data and accompanying data dictionary will be made available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Analytic Code
Time Frame: 6 months

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by A/Prof. Hessom Razavi, Lions Eye Institute, Perth, Western Australia:
Diabetic macular edema
Aboriginal
Australian
Additional relevant MeSH terms:
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Macular Edema
Diabetic Retinopathy
Edema
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Dexamethasone
Bevacizumab
 Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists