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Trial registered on ANZCTR


Registration number
ACTRN12618001102268
Ethics application status
Approved
Date submitted
13/06/2018
Date registered
2/07/2018
Date last updated
2/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Intravitreal dexamethasone for resistant wet-AMD
Scientific title
Intravitreal Dexamethasone in patients with wet age-related macular
degeneration resistant to anti-VEGF: a prospective pilot study.
Secondary ID [1] 295195 0
Nil known
Universal Trial Number (UTN)
U1111-1215-6094
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Resistent choroidal neovascularization 308333 0
Wet aged macular degeneration 308334 0
Condition category
Condition code
Eye 307335 307335 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients belonging to the treatment group were treated with a single Intravitreal dexamethasone injection (700 µg dexamethasone intravitreal
implant) at baseline. Starting from month one, the treatment group continued intravitreal anti-VEGF injection therapy according to the former on-going anti-VEGF intravitreal therapy (ranibizumab 0.5 mg or aflibercept 2 mg) with an as-needed regimen,
No further injections of Intravitreal dexamethasone were administered during the study.
Retreatment criteria for the as-needed regimen with Anti-VEGF drugs were:
BCVA loss greater than, or equal to 5 ETDRS letters
Recurrence or persistence of any fluid in the macula on SD-OCT
A10% increase in CSFT in comparison with the previous value
New macular hemorrhages
New area of classic CNV
Development of new retinal PED or increase in size of an already existent PED
Intervention code [1] 301535 0
Treatment: Drugs
Comparator / control treatment
patients in the control group were evaluated and treated with intravitreal anti-VEGF injection drugs on a monthly basis for 6 months. The Anti-VEGF used were: Ranibizumab (0.05 mL of 10 mg/mL solution) or Aflibercept 2 mg (0.05 mL).
Retreatment criteria for the as-needed regimen with Anti-VEGF drugs were:
BCVA loss greater than, or equal to 5 ETDRS letters
Recurrence or persistence of any fluid in the macula on SD-OCT
A10% increase in CSFT in comparison with the previous value
New macular haemorrhages
New area of classic CNV
Development of new retinal PED or increase in size of an already existent PED
Control group
Active

Outcomes
Primary outcome [1] 306292 0
The Primary outcome was the complete regression of IRF/SRF at SD-OCT (no evidence of
any fluid at each B-scan in both radial and volume pattern).
Timepoint [1] 306292 0
6 months post-baseline assessment (day 15, 30, 60, 90, 120 and 180 - primary endpoint.)
Secondary outcome [1] 348092 0
The safety profile of the treatment was evaluated at day 15, 30, 60, 90, 120 and 180.
To verify this composite secondary outcome at each follow-up visit slit lamp examination, distance best corrected visual acuity (BCVA), intraocular pressure (IOP) measurement by Goldmann applanation tonometry, dilated fundus examination, and SD-OCT were performed to evaluate any possible side/effect. Patients were also investigated for any systemic complications and side effects at each visit.
The possible side effects that may occur are related to the intravitreal injection procedure such as endophthalmitis, glaucoma, subconjunctival haemorrhages, myocardial infarction, Ictus
Timepoint [1] 348092 0
6 months post-baseline assessment (day 15, 30, 60, 90, 120 and 180.)
Secondary outcome [2] 348227 0
The change of median CFT during follow up was investigated at each follow-up visit with OCT. OCT examination was carried out with Heidelberg Spectralis HRA (Heidelberg
Engineering, Heidelberg, Germany); radial scan (24 sections at 6/frame rate of 30° length
and 7.5° apart) and volume scan (20° x 20° at high resolution with a 5/frame rate and 49
sections) were obtained for each patient.
Timepoint [2] 348227 0
6 months post-baseline assessment (day 15, 30, 60, 90, 120 and 180)
Secondary outcome [3] 348228 0
The change of median macular volume at OCT during follow up. OCT examination was carried out with Heidelberg Spectralis HRA (Heidelberg
Engineering, Heidelberg, Germany); radial scan (24 sections at 6/frame rate of 30° length
and 7.5° apart) and volume scan (20° x 20° at high resolution with a 5/frame rate and 49
sections) were obtained for each patient..
Timepoint [3] 348228 0
6 months post-baseline assessment (day 15, 30, 60, 90, 120 and 180)
Secondary outcome [4] 348229 0
Fluorescein angiography (FA) was performed at baseline and at 2 months with Heidelberg
Spectralis HRA. The leakage area was delimited with the Heidelberg Spectralis HRA software at each follow-up and compared at 2 months follow-up.
Timepoint [4] 348229 0
Baseline and at 2 months
Secondary outcome [5] 348230 0
Evaluation of the extension of IS/OS, RPE and ELM damage at OCT scans obtained with Heidelberg Spectralis HRA (Heidelberg Engineering, Heidelberg, Germany) for each patient. at month 2
Timepoint [5] 348230 0
These estimates were carried out on month-2 OCT when the IRF/SRF reduction was
greater and the visualization of external layers improved.

Eligibility
Key inclusion criteria
We enrolled only patients diagnosed with subfoveal AMD-related CNV with evidence of
persistent IRF/SRF, despite at least 4 consecutive monthly injections of anti-VEGF agents,
administered just before inclusion in the study
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Retinopathy other than AMD
Uncontrolled glaucoma (IOP greater than or equal to 25 mmHg)
NVG
Active inflammation and/or infection in the study eye
History of vitrectomy at any time
Cataract surgery within the previous 3 months
On-going therapy with other systemic or intravitreal steroids
Other previous treatment for wet-AMD

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
In this Pilot study, we expect to enrol a maximum of 20 patients (10 per group).
Categorical variables will be performed using absolute frequency
and percentage, while continuous variables will be summarized as mean (standard
deviation- SD) or median (Interquartile Range -IQR), when appropriate. Inferential analysis
of quantitative variables will be also performed with the chi-squared test or the Fisher’s Exact test. After the assessment of their distribution with the Shapiro-Wilk normality test, the differences between continuous variables will be computed with the student t-test or the Wilcoxon test, when appropriate. CFT, BCVA, and IOP at each time point of follow up
will be compared with their respective baseline values using the appropriate test.
Survival analysis with Kaplan-Meyer curves followed by the log-rank test will be performed to evaluate eyes that developed a complete response and those that will not in the treatment and control group, respectively. A p-value < 0.05 will be considered to be statistically significant. Statistical analysis will be carried out using Stata software (Stata/MP 13.0)

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
3/02/2016
Date of last participant enrolment
Anticipated
Actual
23/03/2016
Date of last data collection
Anticipated
Actual
29/09/2016
Sample size
Target
20
Accrual to date
Final
16
Recruitment outside Australia
Country [1] 10559 0
Italy
State/province [1] 10559 0
Sassari

Funding & Sponsors
Funding source category [1] 299784 0
University
Name [1] 299784 0
A.O.U.Sassari
Country [1] 299784 0
Italy
Primary sponsor type
University
Name
A.O.U. Sassari
Address
Viale San Pietro 43 - 07100 Sassari, Italy
Country
Italy
Secondary sponsor category [1] 299131 0
None
Name [1] 299131 0
Address [1] 299131 0
Country [1] 299131 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300671 0
Comitato Etico dell´Azienda Ospedaliera Universitaria di Sassari
Ethics committee address [1] 300671 0
Comitato Etico ATS Sardegna, Via Enrico Costa n. 57 – 07100 - Sassari - Italy
Ethics committee country [1] 300671 0
Italy
Date submitted for ethics approval [1] 300671 0
Approval date [1] 300671 0
19/01/2016
Ethics approval number [1] 300671 0
2286/CE

Summary
Brief summary
The advent of anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy
introduced a new standard of care for patients with neovascular age-related macular
degeneration (wet-AMD). Although anti-VEGFs are effective to prevent severe visual loss
in most cases, often promoting a significant visual improvement, there are some patients
with wet-AMD who continue to experience a visual deterioration despite an adequate
treatment. Long-lasting intraretinal or subretinal fluid (IRF/SRF) may
induce irreversible damage to retinal structures, preventing optimal visual recovery.
Moreover, the need for frequent treatments for prolonged periods adds substantial
burdens and safety concerns for these patients. Inflammation is involved in both the beginning and the progression of AMD. To
counteract inflammation could lead to a better control of this pathology. The
complementary action of intravitreal steroid injections in wet-AMD dates back to the
combination of intravitreal triamcinolone acetonide (TA) with photodynamic therapy
(PDT). The purpose of this study was to evaluate the anatomical and visual outcomes in patients with wet-AMD and persistent IRF/SRF, after adding dexamethasone intravitreal
implant to the already on-going anti-VEGF therapy.
Trial website
Trial related presentations / publications
D'Amico Ricci G, Giancipoli E, Boscia F, Zasa G, Sotgiu G, Dore G,
Pinna A. POSTER PRESENTATION: Dexamethasone intravitreal implant combined with anti-VEGF in patients with neovascular age related macular degeneration resistant
to anti-VEGF alone. Acta Ophthalmologica. 2017; 95:n/a-n/a.
Public notes

Contacts
Principal investigator
Name 84414 0
Prof Francesco Boscia
Address 84414 0
Francesco Bsocia, Clinica Oculistica, 3 Piano, Viale San Pietro 43 - 07100 Sassari - Italy
Country 84414 0
Italy
Phone 84414 0
+39079228250
Fax 84414 0
Email 84414 0
salaoperatoriaoculistica@gmail.com
Contact person for public queries
Name 84415 0
Giuseppe D'Amico Ricci
Address 84415 0
Giuseppe D'Amico Ricci, Clinica Oculistica, 3 Piano, Viale San Pietro 43 - 07100 Sassari - Italy
Country 84415 0
Italy
Phone 84415 0
+39079228250
Fax 84415 0
Email 84415 0
salaoperatoriaoculistica@gmail.com
Contact person for scientific queries
Name 84416 0
Giuseppe D'Amico Ricci
Address 84416 0
Giuseppe D'Amico Ricci, , Clinica Oculistica, 3 Piano, Viale San Pietro 43 - 07100 Sassari - Italy
Country 84416 0
Italy
Phone 84416 0
+39079228250
Fax 84416 0
Email 84416 0
salaoperatoriaoculistica@gmail.com

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