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Trial registered on ANZCTR


Registration number
ACTRN12611001210965
Ethics application status
Approved
Date submitted
14/11/2011
Date registered
24/11/2011
Date last updated
24/11/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
An Open Label Clinical Trial of Ranibizumab for Diabetic Macular Oedema resistant to Intravitreal Triamcinolone
Scientific title
An open label phase II/III clinical trial of Ranibizumab on the effects and safety for diabetic macular oedema resistant to intravitreal triamcinolone (TAREDS)
Secondary ID [1] 273382 0
Nil
Universal Trial Number (UTN)
Trial acronym
TAREDS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic macular oedema 279158 0
Condition category
Condition code
Metabolic and Endocrine 279356 279356 0 0
Diabetes
Eye 279357 279357 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We will, after investigations to exclude any other cause of visual loss, conduct an open label study to administer intravitreal injections of 0.3 mg of ranibizumab at four weekly intervals with a minimum 4 injections planned with additional doses at the same interval if clinically indicated at the discretion of the Investigator for up to 12 months. All patients will be followed for at least 12 months.
Intervention code [1] 283713 0
Treatment: Drugs
Comparator / control treatment
no treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 285945 0
Primary Outcomes
- Proportion of treated eyes with improvement of visual acuity by 5 letters or more on the ETDRS chart up to 12 months
Timepoint [1] 285945 0
12 month
Primary outcome [2] 285948 0
- Incidence of local or systemic, moderate or severe adverse effects possibly related to treatment.
On each visit, the following assessments will be performed:
1. The Best Corrected LogMAR Visual acuity using ETDRS charts will be performed by masked certified BCVA examiner. Any vision change related adverse events (AE) or complications will be accessed and recorded.
2. IOP (applanation). This will detect the IOP increase. IOP increase by 5 mm Hg compare to the baseline or at any time IOP increase over 22 mm HG will be considered as an AE.
3. Cataract grading using Age-Related Eye Disease Study photographic standards. Cataract increases >=2 compare to the baseline will be considered as AE.
4.Ophthalmic examinations including grading of anterior and posterior chamber cells and flare will be performed. This will monitor any inflammation, retinal detachment and other ocular AEs.
5.Vital signs including blood pressure, pause will be monitored and recorded.
6. Other AEs including any ocular and systemic AEs will be accessed. The Conmeds/procedures will also be accessed and recorded.
Timepoint [2] 285948 0
up to 12 month
Secondary outcome [1] 294824 0
- Change in macular thickness by OCT
Timepoint [1] 294824 0
12 month
Secondary outcome [2] 294827 0
- Any change in visual acuity. The Best Corrected LogMAR Visual acuity using ETDRS charts will be performed by masked certified BCVA examiner on patient at each visit.
Timepoint [2] 294827 0
12 month

Eligibility
Key inclusion criteria
All patient with diabetic macular oedema resistant to IVTA treatment.
IVTA resistance is defined as
- An improvement in VA of less than 5 letters
AND
- A reduction in central retinal thickness in OCT of less than 100 microns
(or less than 20%, whichever is greater) 6 weeks after treatment with IVTA for at least 2 consecutive injections.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients
- loss of vision due to other causes (e.g. age related macular degeneration, myopic macular degeneration)
- no useful vision in fellow eye
- cataract surgery or retinal laser within 1st six months of entering the study
- uncontrolled systemic disease including blood pressure>180/110

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patient Orientation
The concept of steroid resistance and proposed open label use of ranibizumab will be explained in detail with particular reference to clinical data from our previous clinical trials of IVTA for macular oedema.
After obtaining the informed consent, we will perform the baseline examinations.
Baseline Examination
The examinations during the visits will include the following:
- Visual Acuity. Best corrected visual acuity will be assessed on LogMAR chart.
- Slit lamp examination for grading of lens opacities and assessment of intraocular pressure.
- Optical coherence tomography (OCT)
- Fundus photography and fluoroscein angiography will be performed at baseline and 12 months visits.
- Visual fields RNFL and other specialised OCT scans and other investigations may be performed as indicated in to exclude other causes of impaired visual acuity such as anterior ischaemic retinopathy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
The major quality assurance features of this study are

- Standardised procedures for patient treatment and evaluation
- Source data verification on 100% of patients for all demographic, safety and efficacy data
- Dual data entry into database.
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] 284195 0
Commercial sector/Industry
Name [1] 284195 0
Novartis Pharmaceuticals Australia Pty Ltd
Address [1] 284195 0
54, Waterloo Road
North Ryde, NSW 2113
Australia
Country [1] 284195 0
Australia
Primary sponsor type
University
Name
the University of Sydney
Address
The University of Sydney, NSW 2006
Country
Australia
Secondary sponsor category [1] 269156 0
None
Name [1] 269156 0
Address [1] 269156 0
Country [1] 269156 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286162 0
SESIAHS Northern Hospital Network Human Research Ethics Committee
Ethics committee address [1] 286162 0
Room G71, East Wing, Edmund Blacket Bldg, Prince Wales hospital, Cnr High and Avoca Streets, Randwick, NSW 2031
Ethics committee country [1] 286162 0
Australia
Date submitted for ethics approval [1] 286162 0
Approval date [1] 286162 0
25/03/2009
Ethics approval number [1] 286162 0
1/08/0130

Summary
Brief summary
Diabetic macular oedema (DMO) is thought to result from a series of biochemical and cellular changes, causing progressive leakage and exudation. Focal and grid photocoagulation remains the standard care for diabetic maculopathy. However, the availability of new agents raises the possibility of improvements in outcomes. Vascular endothelial growth factor (VEGF) levels have been found to be elevated in the aqueous and vitreous humour of patients with DMO.The study is designed to confirm the efficacy and safety of ranibizumab (0.3 mg), an anti-VEGF agent, as therapy in patients with visual impairment due to DMO, in whom current treatments of intravitreal injections of triamcinolone (IVTA) is no longer effective.
The primary objective of this study is to determine whether ranibizumab 0.3 mg given as monthly intravitreal injections is effective in patients who meet the criteria for steroid (IVTA) resistence, defined as:
- An improvement in VA of less than 5 letters
- A reduction in central retinal thickness in OCT of less than 100 microns
(or less than 20%, whichever is greater) 6 weeks after treatment with IVTA for at least 2 consecutive injections

RESEARCH DESIGN AND METHODS
We will, after investigations to exclude any other cause of visual loss, conduct an open label study to administer intravitreal injections of 0.3 mg of ranibizumab at four weekly intervals to all enrolled patients, with a minimum 4 injections planned with additional doses at the same interval if clinically indicated at the discretion of the Investigator for up to 12 months. All patients will be followed for at least 12 months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33385 0
Address 33385 0
Country 33385 0
Phone 33385 0
Fax 33385 0
Email 33385 0
Contact person for public queries
Name 16632 0
Dr Meidong Zhu
Address 16632 0
Save Sight Institute, Department of Clinical Ophthalmology and Eye Health, University of Sydney Sydney/Sydney Eye Hospital Campus, 8 Macquarie Street, NSW 2000
Country 16632 0
Australia
Phone 16632 0
+61 2 93827286
Fax 16632 0
+61 2 93827278
Email 16632 0
meidong.zhu@sydney,edu,au
Contact person for scientific queries
Name 7560 0
Professor Mark Gillies
Address 7560 0
Save Sight Institute, Department of Clinical Ophthalmology and Eye Health, University of Sydney Sydney/Sydney Eye Hospital Campus, 8 Macquarie Street, NSW 2000
Country 7560 0
Australia
Phone 7560 0
+61 412060313
Fax 7560 0
+61 2 93827278
Email 7560 0
mark.gillies@sydney.edu.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary