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Trial registered on ANZCTR


Trial ID
ACTRN12605000245695
Ethics application status
Approved
Date submitted
22/08/2005
Date registered
31/08/2005
Date last updated
29/05/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
A multicentre randomised clinical trial of laser treatment plus intravitreal triamcinolone for diabetic macular oedema (Thunderbird)
Scientific title
A multicentre randomised clinical trial of laser treatment plus 4 mg intravitreal triamcinolone injection to reduce diabetic macular oedema
Universal Trial Number (UTN)
Trial acronym
Thunderbird
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic macular oedema 332 0
Condition category
Condition code
Metabolic and Endocrine 382 382 0 0
Diabetes
Eye 383 383 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The purpose of this study is to conduct a prospective, multicentre, randomised, double-masked, placebo-controlled, clinical trial of intravitreal triamcinolone (IVTA) plus laser treatment versus laser treatment alone for diabetic macular edema, to determine whether intravitreal steroids will be beneficial if they are used earlier in the course of DMO in conjunction with laser treatment.
we propose that pretreatment with intravitreal triamcinolone of an eye with macular oedema will allow laser treatment to be applied more accurately and with lower power, resulting in greater reduction of oedema and better visual outcomes. Laser treatment after the instillation of the triamcinolone will also reduce the risk of the oedema recurring as the steroid wears off.
Study treatment with intravitreal triamcinolone or placebo will be administered within one week of the baseline angiogram and OCT and on the day of the baseline visual acuity measurement. Triamcinolone (0.1 ml Kenacort 40, 40mg/ml triamcinolone acetate, Bristol-Myers Squibb pharmaceuticals, Australia) will be injected into the vitreous.
All eyes will receive laser treatment according to a standardised protocol 6 weeks after the injection of triamcinolone or placebo based on the distribution of the leak that was demonstrated by the baseline fluorescein angiogram. Treatment will be applied irrespective of whether the macular oedema is still present or not.
The duration of the patient follow-up is 2 years and the duration of the entire study is 3.5 years.
Intervention code [1] 223 0
Treatment: Drugs
Comparator / control treatment
Eyes randomized to receive placebo will be prepared the same way but only balanced salt solution will be administered subconjunctivally.
Control group
Placebo

Outcomes
Primary outcome [1] 440 0
The proportion of eyes showing an improvement of visual acuity by 10 letters on a LogMAR chart compared with the pre-injection level 24 months after treatment
Timepoint [1] 440 0
24 months after treatment
Primary outcome [2] 441 0
The incidence of moderate or severe side effects related to the procedure of intravitreal injection or related to the drug
Timepoint [2] 441 0
up to 24 months after treatment
Secondary outcome [1] 970 0
Any change in visual acuity compared with the pre-injection level
Timepoint [1] 970 0
Within 24 months from the baseline.
Secondary outcome [2] 971 0
Number of laser treatments required for the treatment of macular oedema
Timepoint [2] 971 0
During the 2 year study.
Secondary outcome [3] 972 0
Change in retinal thickness demonstrated on optical coherence tomography (OCT)
Timepoint [3] 972 0
During the 2 year study.

Eligibility
Key inclusion criteria
Diagnosis of diabetes mellitus types 1 or 2Diabetic macular oedema affecting the fovea in one or both eyes (phakic or pseudophakic) for which laser treatment is indicated in the opinion of the investigator. Best corrected visual acuity of 19-68 letters (6/12 6/120)Retinal thickness > 250 micron in central 1mm subfield on OCTInvestigator is comfortable deferring macular laser treatment for 6 weeksIntraocular pressure <22mmHg
Minimum age
18 Years
Maximum age
Not stated
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Glaucoma which is uncontrolled or is controlled but with more than one medication or with only one medication and with glaucomatous field defects Loss of vision due to other causes (e.g. age related macular degeneration, myopic macular degeneration, retinal vein occlusion)Macular oedema due to other causes including vitreous tractionAn ocular condition that would prevent visual acuity improvement despite resolution of oedema (such as foveal atrophy)Treatment with IVTA within the last 6 months or peribulbar TA within the last 3 months.Cataract surgery within the last 6 monthsRetinal laser treatment within the last 4 monthsHistory of pars plana vitrectomy or retinal detachment surgeryHigh risk proliferative diabetic retinopathy at baseline visit that laser cannot be delayed for 6 week on retinaHistory of herpes viral disease in study eyeMedia opacity including cataract that already precludes adequate macular photography and laser treatment, or cataract that is likely to require surgery within 2 yearsKnown allergies to triamcinolone acetatePatient is already receiving systemic steroid treatmentIntercurrent severe disease such as septicemia, any condition which would affect follow-up or photographic documentation (e.g. geographical, psycho-social)History of chronic renal failure requiring dialysis or renal transplantBlood pressure >180/110.

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)
After signing the informed consent form, each patient will be randomized to receive study treatment using a series of serially numbered, opaque envelopes containing an assignment to treat or placebo. Treatment assignments will be compiled using a list of computer generated pseudo-random numbers in permuted blocks of variable size. The identification of patients will consist of a code made up of the patient’s initials and number. Observers assessing best corrected visual acuity will be masked to treatment allocation, as well the investigator who performs laser treatment and decides whether further treatment is indicated or not. The surgeon performing the injections will be unmasked to treatment allocation. The photographer and OCT operators need not be masked.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients are randomized to receive study treatment using a series of serially numbered, opaque envelopes containing an assignment to treat or placebo. Treatment assignments will be compiled using a list of computer generated pseudo-random numbers in permuted blocks of variable size. In patients with only one eye eligible for the study, the eye will be randomised to receive treatment with intravitreal triamcinolone or a placebo sub-conjunctival injection. In patients with both eyes eligible for the study, the right eye will receive the treatment assignment in the envelope and the fellow eye will receive the reverse treatment.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 436 0
Government body
Name [1] 436 0
NHMRC project grant 352312
Address [1] 436 0
Australia
Country [1] 436 0
Australia
Primary sponsor type
Individual
Name
Associate Professor Mark C Gillies
Address
Save Sight Institute
Department of Clinical Ophthalmology and Eye Health
Country
Australia
Secondary sponsor category [1] 354 0
None
Name [1] 354 0
No
Address [1] 354 0
Country [1] 354 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1405 0
SESIAHS Northern Network Human Research Ethics Committee
Ethics committee address [1] 1405 0
Sydney NSW
Ethics committee country [1] 1405 0
Australia
Date submitted for ethics approval [1] 1405 0
Approval date [1] 1405 0
01/10/2004
Ethics approval number [1] 1405 0
04/270
Ethics committee name [2] 1406 0
Centre for Eye Research Australia,
Ethics committee address [2] 1406 0
Melbourne VIC
Ethics committee country [2] 1406 0
Australia
Date submitted for ethics approval [2] 1406 0
Approval date [2] 1406 0
01/01/2005
Ethics approval number [2] 1406 0
Ethics committee name [3] 1407 0
Lions Eye Institute,
Ethics committee address [3] 1407 0
Perth SA
Ethics committee country [3] 1407 0
Australia
Date submitted for ethics approval [3] 1407 0
Approval date [3] 1407 0
Ethics approval number [3] 1407 0
Ethics committee name [4] 1408 0
Eye Clinic, Westmead Hospital,
Ethics committee address [4] 1408 0
Westmead, NSW
Ethics committee country [4] 1408 0
Australia
Date submitted for ethics approval [4] 1408 0
Approval date [4] 1408 0
Ethics approval number [4] 1408 0
Ethics committee name [5] 1409 0
Marsden Eye Specialists,
Ethics committee address [5] 1409 0
Parramatta, NSW
Ethics committee country [5] 1409 0
Australia
Date submitted for ethics approval [5] 1409 0
Approval date [5] 1409 0
Ethics approval number [5] 1409 0

Summary
Brief summary
Each study sites will apply for their own ethics approval from their local ethics committee. All study sites have been granted approval.
Trial website
Trial related presentations / publications
1. Gillies MC, Islam FM, Zhu M, Larsson J, Wong TY. Efficacy and safety of multiple intravitreal triamcinolone injections for refractory diabetic macular oedema. Br J Ophthalmol. 2007;91(10):1323-6. (IF:2.524)
2. Gillies M. Intravitreal triamcinolone for diabetic macular edema. Ophthalmology In Press accepted 18.12.08.
3. Wickremasinghe SS, Rogers SL, Gillies MC, Zhu M, Wong TY. Retinal Vascular Caliber Changes after Intravitreal Triamcinolone Treatment for Diabetic Macular Edema. Invest Ophthalmol Vis Sci 2008 Nov;49(11):4707-11. Epub 2008 Jul 3. (IF:3.766)
Public notes

Contacts
Principal investigator
Name 35343 0
Address 35343 0
Country 35343 0
Phone 35343 0
Fax 35343 0
Email 35343 0
Contact person for public queries
Name 9412 0
Dr Meidong Zhu
Address 9412 0
Save Sight Institute
Department of Clinical Ophthalmology and Eye Health
University of Sydney
Sydney/Sydney Eye Hospital Campus
GPO Box 4337
NSW 2001
Country 9412 0
Australia
Phone 9412 0
+61 2 93827286
Fax 9412 0
+61 2 93827318
Email 9412 0
meidong@eye.usyd.edu.au
Contact person for scientific queries
Name 340 0
Professor Mark Gillies
Address 340 0
Save Sight Institute, Department of Clinical Save Sight Institute
Department of Clinical Ophthalmology and Eye Health
University of Sydney
Sydney/Sydney Eye Hospital Campus
GPO Box 4337
NSW 2001
Country 340 0
Australia
Phone 340 0
+61 2 93827309
Fax 340 0
+61 2 93827318
Email 340 0
mark@eye.usyd.edu.au