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

November 5, 2020 updated by: A/Prof. Hessom Razavi, Lions Eye Institute, Perth, Western Australia

A Randomized Clinical Trial of Intravitreal dexamethasOne Versus Bevacizumab in Aboriginal and Torres Strait Islander patientS With Diabetic Macular Oedema (The OASIS Study)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

59

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Western Australia
      • Broome, Western Australia, Australia, 6725
        • Broome Regional Aboriginal Medical Service
      • Derby, Western Australia, Australia, 6728
        • Derby Hospital
      • Fitzroy Crossing, Western Australia, Australia, 6728
        • Fitzroy Crossing Hospital
      • Halls Creek, Western Australia, Australia, 6770
        • Halls Creek Health Service
      • Kalgoorlie, Western Australia, Australia, 6430
        • Bega Garnbirringu Health Service
      • Karratha, Western Australia, Australia, 6714
        • Nickol Bay Hospital
      • Kununurra, Western Australia, Australia, 6743
        • Ord Valley Aboriginal Health Service
      • Laverton, Western Australia, Australia, 6440
        • Laverton Hospital
      • Perth, Western Australia, Australia, 6004
        • Derbarl Yerrigan Health Service Inc.
      • Perth, Western Australia, Australia, 6009
        • Lions Eye Institute Nedlands
      • Perth, Western Australia, Australia, 6056
        • Lions Eye Institute Midland
      • Roebourne, Western Australia, Australia, 6718
        • Mawarnkarra Health Service
      • South Hedland, Western Australia, Australia, 6722
        • Wirraka Maya Health Service Aboriginal Corporation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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 Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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').
12 months
Change in central macular thickness
Time Frame: 12 months
Change in the CMT from baseline to 12 months as measured by OCT.
12 months
Number of injections
Time Frame: 12 months
Number of IVT injections given per participant.
12 months
Appointments attended
Time Frame: 12 months
Number of appointments attended per participant.
12 months
Intraocular pressure change
Time Frame: 12 months
The change in the mean IOP.
12 months
Intraocular pressure elevation
Time Frame: 12 months
The number of participants with one or more occasions of IOP elevation >28 mmHg.
12 months
Intraocular pressure elevation requiring treatment
Time Frame: 12 months
IOP elevation requiring medical, laser or surgical treatment.
12 months
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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lions Eye Institute, Perth, Western Australia

Collaborators

Allergan
Lions Outback Vision

Investigators

  • Study Director: Angus Turner, FRANZCO, Lions Eye Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2017

Primary Completion (Actual)

February 14, 2020

Study Completion (Actual)

February 14, 2020

Study Registration Dates

First Submitted

October 27, 2020

First Submitted That Met QC Criteria

November 5, 2020

First Posted (Actual)

November 6, 2020

Study Record Updates

Last Update Posted (Actual)

November 9, 2020

Last Update Submitted That Met QC Criteria

November 5, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OASIS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Time Frame

6 months

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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