Intravitreal Dexamethasone vs Bevacizumab in Aboriginal People With DMO

NCT04619303 | Completed Phase 4

• 1 other identifier: OASIS
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 13

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.

Conditions

Diabetic Macular Edema; Diabetic Retinopathy

Keywords

Diabetic macular edema; Aboriginal; Australian

Outcome Measures

Primary Outcomes (1)

• Difference in best corrected visual acuity change between treatment arms

  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 Outcomes (8)

• Best corrected visual acuity loss or gain

  12 months

• Change in central macular thickness

  12 months

• Number of injections

  12 months

• Appointments attended

  12 months

• Intraocular pressure change

  12 months

Study Arms (2)

Dexamethasone Implant

EXPERIMENTAL

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

Bevacizumab

ACTIVE COMPARATOR

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

Interventions

Dexamethasone intravitreal implant DRUG

Intravitreal injection of 0.7mg dexamethasone implant

Also known as: Ozurdex, DEX-implant

Dexamethasone Implant

Bevacizumab Injectable Product DRUG

Invtravitreal injection of 1.25mg/0.05mL bevacizumab

Also known as: Avastin

Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lions Eye Institute, Perth, Western Australia: lead
• Lions Outback Vision: collaborator
• Allergan: collaborator

Study Sites (13)

Broome Regional Aboriginal Medical Service

Broome, Western Australia, 6725, Australia

Location

Derby Hospital

Derby, Western Australia, 6728, Australia

Location

Fitzroy Crossing Hospital

Fitzroy Crossing, Western Australia, 6728, Australia

Location

Halls Creek Health Service

Halls Creek, Western Australia, 6770, Australia

Location

Bega Garnbirringu Health Service

Kalgoorlie-Boulder, Western Australia, 6430, Australia

Location

Nickol Bay Hospital

Karratha, Western Australia, 6714, Australia

Location

Ord Valley Aboriginal Health Service

Kununurra, Western Australia, 6743, Australia

Location

Laverton Hospital

Laverton, Western Australia, 6440, Australia

Location

Derbarl Yerrigan Health Service Inc.

Perth, Western Australia, 6004, Australia

Location

Lions Eye Institute Nedlands

Perth, Western Australia, 6009, Australia

Location

Lions Eye Institute Midland

Perth, Western Australia, 6056, Australia

Location

Mawarnkarra Health Service

Roebourne, Western Australia, 6718, Australia

Location

Wirraka Maya Health Service Aboriginal Corporation

South Hedland, Western Australia, 6722, Australia

Location

Related Publications (23)

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• Wong J, Molyneaux L, Constantino M, Twigg SM, Yue DK. Timing is everything: age of onset influences long-term retinopathy risk in type 2 diabetes, independent of traditional risk factors. Diabetes Care. 2008 Oct;31(10):1985-90. doi: 10.2337/dc08-0580. Epub 2008 Jul 15.

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• Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.

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• Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985 Dec;103(12):1796-806.

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• Michaelides M, Kaines A, Hamilton RD, Fraser-Bell S, Rajendram R, Quhill F, Boos CJ, Xing W, Egan C, Peto T, Bunce C, Leslie RD, Hykin PG. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology. 2010 Jun;117(6):1078-1086.e2. doi: 10.1016/j.ophtha.2010.03.045. Epub 2010 Apr 22.

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• Diabetic Retinopathy Clinical Research Network; Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. Epub 2010 Apr 28.

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• Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, Glassman AR, Scott IU, Stockdale CR, Sun JK; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):609-14. doi: 10.1016/j.ophtha.2010.12.033.

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• Al Dhibi HA, Arevalo JF. Clinical trials on corticosteroids for diabetic macular edema. World J Diabetes. 2013 Dec 15;4(6):295-302. doi: 10.4239/wjd.v4.i6.295.

  PMID: 24379920 BACKGROUND

• Chew EY, Benson WE, Remaley NA, Lindley AA, Burton TC, Csaky K, Williams GA, Ferris FL 3rd. Results after lens extraction in patients with diabetic retinopathy: early treatment diabetic retinopathy study report number 25. Arch Ophthalmol. 1999 Dec;117(12):1600-6. doi: 10.1001/archopht.117.12.1600.

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• Cetin EN, Yildirim C. Adjuvant treatment modalities to control macular edema in diabetic patients undergoing cataract surgery. Int Ophthalmol. 2013 Oct;33(5):605-10. doi: 10.1007/s10792-012-9695-1. Epub 2012 Dec 18.

  PMID: 23248073 BACKGROUND

• 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.

  PMID: 20702826 BACKGROUND

• Zalewski D, Raczynska D, Raczynska K. Five-month observation of persistent diabetic macular edema after intravitreal injection of Ozurdex implant. Mediators Inflamm. 2014;2014:364143. doi: 10.1155/2014/364143. Epub 2014 Feb 10.

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• Dutra Medeiros M, Postorino M, Navarro R, Garcia-Arumi J, Mateo C, Corcostegui B. Dexamethasone intravitreal implant for treatment of patients with persistent diabetic macular edema. Ophthalmologica. 2014;231(3):141-6. doi: 10.1159/000356413. Epub 2013 Dec 19.

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• Zucchiatti I, Lattanzio R, Querques G, Querques L, Del Turco C, Cascavilla ML, Bandello F. Intravitreal dexamethasone implant in patients with persistent diabetic macular edema. Ophthalmologica. 2012;228(2):117-22. doi: 10.1159/000336225. Epub 2012 Feb 3.

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• Boyer DS, Faber D, Gupta S, Patel SS, Tabandeh H, Li XY, Liu CC, Lou J, Whitcup SM; Ozurdex CHAMPLAIN Study Group. Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina. 2011 May;31(5):915-23. doi: 10.1097/IAE.0b013e318206d18c.

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Related Links

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

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

Dexamethasone; Calcium Dobesilate; Bevacizumab

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Angus Turner, FRANZCO

  Lions Eye Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: November 6, 2020
• Study Start: February 7, 2017
• Primary Completion: February 14, 2020
• Study Completion: February 14, 2020
• Last Updated: November 9, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: 6 months

Locations

AU (13)