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Trial registered on ANZCTR


Registration number
ACTRN12615000830594
Ethics application status
Approved
Date submitted
28/07/2015
Date registered
11/08/2015
Date last updated
11/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The Influence of Plasma and Aqueous Cytokine Concentrations on the Efficacy of Intravitreal Ranibizumab for the Treatment of Diabetic Macular Oedema
Scientific title
The Influence of Plasma and Aqueous Cytokine Concentrations on the Efficacy of Intravitreal Ranibizumab for the Treatment of Diabetic Macular Oedema.
Secondary ID [1] 287161 0
Nil
Universal Trial Number (UTN)
U1111-1172-6184
Trial acronym
DISCERN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Oedema 295728 0
Condition category
Condition code
Eye 296006 296006 0 0
Diseases / disorders of the eye
Metabolic and Endocrine 296070 296070 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All eligible participants will receive treatment with ranibizumab 0.5mg in 50 microliters for intravitreal injection.
All participants will undergo three consecutive, monthly injections, followed by an as required dosing schedule (PRN) for the 12 month duration of the trial.
Intervention code [1] 292435 0
Treatment: Drugs
Comparator / control treatment
All patients will receive Intravitreal Ranibizumab, the influence of plasma and aqueous cytokine concentrations on the efficacy of the intervention will be measured.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295677 0
To assess if aqueous and plasma cytokine concentrations of angiogenic/inflammatory cytokines correlate with the change in mean best-corrected visual acuity from baseline to 12 months.
Best-corrected visual acuity will be assessed on a LogMAR chart.
Timepoint [1] 295677 0
12 months after first ranibizumab injection or the baseline visit.
Secondary outcome [1] 316195 0
To assess if aqueous and plasma cytokine concentrations correlate with the change in mean best-corrected visual acuity from baseline to 6 months. Best-corrected visual acuity will be assessed on a LogMAR chart.
Timepoint [1] 316195 0
6 months after first ranibizumab injection or the baseline visit.
Secondary outcome [2] 316196 0
To assess if aqueous and plasma cytokine concentrations correlate with the number of ranibizumab injections administered by 6 months
Timepoint [2] 316196 0
6 months after first ranibizumab injection or the baseline visit.
Secondary outcome [3] 316197 0
To assess if aqueous and plasma cytokine concentrations correlate with the change in mean central macular thickness, as measured by Heidelberg Optical Coherence Tomography, from baseline to 6 months.
Timepoint [3] 316197 0
6 months after the first ranibizumab injection or the baseline visit.
Secondary outcome [4] 316198 0
To assess if aqueous and plasma cytokine concentrations correlate with the number of ranibizumab injections given by 12 months
Timepoint [4] 316198 0
12 months after the first ranibizumab injection or the baseline visit.
Secondary outcome [5] 316199 0
To assess if aqueous and plasma cytokine concentrations correlate with the likelihood of recurrent diabetic macular oedema after cessation of ranibizumab. Central macular thickness or macular oedema will be measured by Heidelberg Optical Coherence Tomography.
Timepoint [5] 316199 0
12 months after first ranibizumab injection or baseline visit.
Secondary outcome [6] 316200 0
To assess if aqueous and plasma cytokine concentrations correlate with the length of time from baseline to vision stabilization, leading to cessation of ranibizumab. Whereby vision stabilization is defined as:
-No further BCVA improvement from treatment at the last 2 consecutive follow up visits OR
-BCVA letter score >84 (6/6) at the last 2 consecutive follow up visits.
Timepoint [6] 316200 0
12 months after first ranibizumab injection or baseline visit.
Secondary outcome [7] 316201 0
To assess if aqueous and plasma cytokine concentrations correlate with the mean change in macular thickness from baseline to 12 months. Central macular thickness or macular oedema will be measured by Heidelberg Optical Coherence Tomography.
Timepoint [7] 316201 0
12 months after the first ranibizumab injection or baseline visit.
Secondary outcome [8] 316202 0
To assess if aqueous and plasma cytokine concentrations correlate with the need for rescue therapy. Participants who fail to demonstrate at least a 10% improvement in central macular thickness from baseline despite at least six, monthly injections or where BCVA worsens and in the investigators opinion, vision loss is secondary to DME, will be considered for rescue treatment.
Timepoint [8] 316202 0
12 months after the first ranibizumab injection or baseline visit.
Secondary outcome [9] 316203 0
To assess if the change in aqueous and plasma cytokine concentrations from baseline to month 2 correlates with change in central macular thickness from baseline to 12 months. Central macular thickness or macular oedema will be measured by Heidelberg Optical Coherence Tomography.
Timepoint [9] 316203 0
12 months after the first ranibizumab injection or baseline visit.

Eligibility
Key inclusion criteria
-Age >18 years
-Centre-involving diabetic macular oedema that in the opinion of the investigator, would not benefit from macular laser treatment (eg diffuse leak from the capillary bed, disruption of the foveal avascular zone or perifoveal capillary dropout) as determined by fluorescein angiography
-Best-corrected visual acuity (BCVA) of 17-70 letters (6/12 –6/120)
-Central macular thickness of >300 microns as measured by Heidelberg Optical coherence tomography.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Systemic
-Uncontrolled blood pressure (>180 mmHg, systolic and 110 mmHg, diastolic)
-Chronic renal failure
-Major surgery within one month of study
-Previous systemic anti-VEGF treatment
-Women of childbearing potential not using adequate contraception and women who are breast feeding
-Intercurrent severe disease such as septicaemia

Ocular
-Glaucoma which is uncontrolled or is controlled but with glaucomatous visual field defects
-Past history of severe steroid response with IOP > 35 mmHg following steroid treatment
-Loss of vision due to other causes (e.g. age-related macular degeneration, myopic macular degeneration)
-VA of <6/60 in the fellow eye
-Argon laser photocoagulation within 3 months of study entry
-Previous intraocular surgery (within 6 months)
-Prior use of intravitreal anti-VEGF agents (within 3 months) or corticosteroids (within 6 months)
-Stroke or myocardial infarction less than 3 months prior to screening.
-Any active periocular or ocular infection or inflammation at screening or baseline.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
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)
VIC
Recruitment hospital [1] 4114 0
The Royal Victorian Eye and Ear Hospital - East Melbourne
Recruitment postcode(s) [1] 10040 0
3002 - East Melbourne

Funding & Sponsors
Funding source category [1] 291731 0
Commercial sector/Industry
Name [1] 291731 0
Novartis Pharmaceuticals Australia Pty Ltd
Address [1] 291731 0
54 Waterloo Rd, Macquarie Park NSW 2113
Country [1] 291731 0
Australia
Primary sponsor type
University
Name
The Centre for Eye Research Australia (The University of Melbourne)
Address
Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002
Country
Australia
Secondary sponsor category [1] 290406 0
None
Name [1] 290406 0
Nil
Address [1] 290406 0
Country [1] 290406 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293253 0
The Royal Victorian Eye and Ear Hospital Human Research and Ethics Committee
Ethics committee address [1] 293253 0
32 Gisborne Street, East Melbourne, VIC, 3002
Ethics committee country [1] 293253 0
Australia
Date submitted for ethics approval [1] 293253 0
Approval date [1] 293253 0
22/07/2013
Ethics approval number [1] 293253 0
13/1123H

Summary
Brief summary
We hypothesize that the underlying pathogenesis of Diabetic Macular Oedema (DMO) may be related to a combination of inflammatory and angiogenic cytokines. Although anti-VEGF agents are commonly used for the treatment of DMO, either as a primary measure or more usually in refractory cases, the response to treatment is unpredictable.
We propose that measurement of known diabetes association cytokines may allow accurate prediction of response to anti-VEGF treatment and allow a more individualised treatment strategy for patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59102 0
Dr Sanjeewa Wickremasinghe
Address 59102 0
Centre for Eye Research Australia Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002
Country 59102 0
Australia
Phone 59102 0
+61 3 9929 8076
Fax 59102 0
+61 3 9929 8030
Email 59102 0
sanj.wickremasinghe@eyeandear.org.au
Contact person for public queries
Name 59103 0
Ms Sutha Sanmugasundram
Address 59103 0
Centre for Eye Research Australia, Level 7, 32 Gisborne Street, East Melbourne, VIC 3002
Country 59103 0
Australia
Phone 59103 0
+61 3 9929 8076
Fax 59103 0
+61 3 9929 8030
Email 59103 0
Sans@unimelb.edu.au
Contact person for scientific queries
Name 59104 0
Dr Sanjeewa Wickremasinghe
Address 59104 0
Centre for Eye Research Australia Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002
Country 59104 0
Australia
Phone 59104 0
+61 3 9929 8076
Fax 59104 0
+61 3 9929 8030
Email 59104 0
sanj.wickremasinghe@eyeandear.org.au

No information has been provided regarding IPD availability
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