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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04619303




Registration number
NCT04619303
Ethics application status
Date submitted
27/10/2020
Date registered
6/11/2020
Date last updated
9/11/2020

Titles & IDs
Public title
Intravitreal Dexamethasone vs Bevacizumab in Aboriginal People With DMO
Scientific title
A Randomized Clinical Trial of Intravitreal dexamethasOne Versus Bevacizumab in Aboriginal and Torres Strait Islander patientS With Diabetic Macular Oedema (The OASIS Study)
Secondary ID [1] 0 0
OASIS
Universal Trial Number (UTN)
Trial acronym
OASIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Edema 0 0
Diabetic Retinopathy 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Metabolic and Endocrine 0 0 0 0
Diabetes
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dexamethasone intravitreal implant
Treatment: Drugs - Bevacizumab Injectable Product

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.

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.


Treatment: Drugs: Dexamethasone intravitreal implant
Intravitreal injection of 0.7mg dexamethasone implant

Treatment: Drugs: Bevacizumab Injectable Product
Invtravitreal injection of 1.25mg/0.05mL bevacizumab
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Difference in best corrected visual acuity change between treatment arms
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Best corrected visual acuity loss or gain
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
Change in central macular thickness
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Number of injections
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Appointments attended
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Intraocular pressure change
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Intraocular pressure elevation
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Intraocular pressure elevation requiring treatment
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Adverse Events
Timepoint [8] 0 0
12 months

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/02/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/02/2020
Sample size
Target
Accrual to date
Final
59
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Broome Regional Aboriginal Medical Service - Broome
Recruitment hospital [2] 0 0
Derby Hospital - Derby
Recruitment hospital [3] 0 0
Fitzroy Crossing Hospital - Fitzroy Crossing
Recruitment hospital [4] 0 0
Halls Creek Health Service - Halls Creek
Recruitment hospital [5] 0 0
Bega Garnbirringu Health Service - Kalgoorlie
Recruitment hospital [6] 0 0
Nickol Bay Hospital - Karratha
Recruitment hospital [7] 0 0
Ord Valley Aboriginal Health Service - Kununurra
Recruitment hospital [8] 0 0
Laverton Hospital - Laverton
Recruitment hospital [9] 0 0
Derbarl Yerrigan Health Service Inc. - Perth
Recruitment hospital [10] 0 0
Lions Eye Institute Nedlands - Perth
Recruitment hospital [11] 0 0
Lions Eye Institute Midland - Perth
Recruitment hospital [12] 0 0
Mawarnkarra Health Service - Roebourne
Recruitment hospital [13] 0 0
Wirraka Maya Health Service Aboriginal Corporation - South Hedland
Recruitment postcode(s) [1] 0 0
6725 - Broome
Recruitment postcode(s) [2] 0 0
6728 - Derby
Recruitment postcode(s) [3] 0 0
6728 - Fitzroy Crossing
Recruitment postcode(s) [4] 0 0
6770 - Halls Creek
Recruitment postcode(s) [5] 0 0
6430 - Kalgoorlie
Recruitment postcode(s) [6] 0 0
6714 - Karratha
Recruitment postcode(s) [7] 0 0
6743 - Kununurra
Recruitment postcode(s) [8] 0 0
6440 - Laverton
Recruitment postcode(s) [9] 0 0
6004 - Perth
Recruitment postcode(s) [10] 0 0
6009 - Perth
Recruitment postcode(s) [11] 0 0
6056 - Perth
Recruitment postcode(s) [12] 0 0
6718 - Roebourne
Recruitment postcode(s) [13] 0 0
6722 - South Hedland

Funding & Sponsors
Primary sponsor type
Other
Name
Lions Eye Institute, Perth, Western Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Lions Outback Vision
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Allergan
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04619303
Trial related presentations / publications
Xie J, Arnold AL, Keeffe J, Goujon N, Dunn RA, Fox S, Taylor HR. Prevalence of self-reported diabetes and diabetic retinopathy in indigenous Australians: the National Indigenous Eye Health Survey. Clin Exp Ophthalmol. 2011 Aug;39(6):487-93. doi: 10.1111/j.1442-9071.2011.02502.x. Epub 2011 Mar 24.
Kaidonis G, Mills RA, Landers J, Lake SR, Burdon KP, Craig JE. Review of the prevalence of diabetic retinopathy in Indigenous Australians. Clin Exp Ophthalmol. 2014 Dec;42(9):875-82. doi: 10.1111/ceo.12338. Epub 2014 May 5.
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.
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.
Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. Ophthalmology. 1995 Apr;102(4):647-61. doi: 10.1016/s0161-6420(95)30973-6.
Wong TY, Mwamburi M, Klein R, Larsen M, Flynn H, Hernandez-Medina M, Ranganathan G, Wirostko B, Pleil A, Mitchell P. Rates of progression in diabetic retinopathy during different time periods: a systematic review and meta-analysis. Diabetes Care. 2009 Dec;32(12):2307-13. doi: 10.2337/dc09-0615.
Klein R, Klein BE. Blood pressure control and diabetic retinopathy. Br J Ophthalmol. 2002 Apr;86(4):365-7. doi: 10.1136/bjo.86.4.365. No abstract available.
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.
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.
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.
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.
Dewan V, Lambert D, Edler J, Kymes S, Apte RS. Cost-effectiveness analysis of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2012 Aug;119(8):1679-84. doi: 10.1016/j.ophtha.2012.01.049. Epub 2012 Apr 13.
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.
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.
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.
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.
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.
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.
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.
Haller JA, Kuppermann BD, Blumenkranz MS, Williams GA, Weinberg DV, Chou C, Whitcup SM; Dexamethasone DDS Phase II Study Group. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol. 2010 Mar;128(3):289-96. doi: 10.1001/archophthalmol.2010.21.
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.
Hariprasad SM, Mieler WF, Grassi M, Green JL, Jager RD, Miller L. Vision-related quality of life in patients with diabetic macular oedema. Br J Ophthalmol. 2008 Jan;92(1):89-92. doi: 10.1136/bjo.2007.122416. Epub 2007 Jun 21.
Chen E, Looman M, Laouri M, Gallagher M, Van Nuys K, Lakdawalla D, Fortuny J. Burden of illness of diabetic macular edema: literature review. Curr Med Res Opin. 2010 Jul;26(7):1587-97. doi: 10.1185/03007995.2010.482503.
Public notes

Contacts
Principal investigator
Name 0 0
Angus Turner, FRANZCO
Address 0 0
Lions Eye Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04619303