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Trial registered on ANZCTR


Registration number
ACTRN12618000697280
Ethics application status
Approved
Date submitted
30/11/2017
Date registered
30/04/2018
Date last updated
30/04/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluation of the evolution of patients with vitreous hemorrhage caused by proliferative diabetic retinopathy subjected to intravitreal injection of antivascular endothelial growth factor (bevacizumab)
Scientific title
Evaluation of the evolution of patients with vitreous hemorrhage caused by proliferative diabetic retinopathy subjected to intravitreal injection of antivascular endothelial growth factor (bevacizumab)
Secondary ID [1] 293451 0
Nil known
Universal Trial Number (UTN)
U1111-1205-7536
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
proliferative diabetic retinopathy 305677 0
vitreous hemorrhage 305678 0
Condition category
Condition code
Metabolic and Endocrine 304899 304899 0 0
Diabetes
Eye 305731 305731 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
intravitreal injection of antivascular endothelial growth factor (bevacizumab) - 1,25 mg (0,05 mL) performed by ophthalmologist
Initial injection must be given on the day of randomization. Follow-up injections will be performed as often as every 4 weeks (based on the time recommended for treatment of other ocular pathologies with bevacizumab) with a maximum of 6 injections provided and a minimum of 3 injections ( if criteria for deferral are met, that is reabsorption of vitreous hemorrhage that allows photocoagulation) until six months of follow-up,
Intervention code [1] 299731 0
Treatment: Drugs
Comparator / control treatment
simulated intravitreal injections -

Initial simulated injection (there is no actual injection, only simulation with needle-free syringe complete with air) , must be given on the day of randomization. Follow-up simulated injections will be performed as often as every 4 weeks unless criteria for deferral are met, until six months of accompaniment
Control group
Placebo

Outcomes
Primary outcome [1] 304092 0
Absorption of vitreous hemorrhage enabling photocoagulation (Classification 0-2 according to the table below)


5- No vision of retina or optic disk
4- Optic disk view only
3- Vision of optic disk and large arcade vases, without conditions for photocoagulation
2- Vitreous hemorrhage located by quadrant with retinal and vases vision enough to make laser in 1-2 quadrants
1- Vitreous hemorrhage located by quadrant with retinal and vases vision enough to make laser in 3-4 quadrants
0- Peripheral vitreous hemorrhage that does not prevent laser
Timepoint [1] 304092 0
at six months after randomisation
Primary outcome [2] 304093 0
Percentage of patients who did not need vitrectomy (with a vitrectomy required if vitreous hemorrhage classification equal or more than a score of 3 according to the table below).


5- No vision of retina or optic disk
4- Optic disk view only
3- Vision of optic disk and large arcade vases, without conditions for photocoagulation
2- Vitreous hemorrhage located by quadrant with retinal and vases vision enough to make laser in 1-2 quadrants
1- Vitreous hemorrhage located by quadrant with retinal and vases vision enough to make laser in 3-4 quadrants
0- Peripheral vitreous hemorrhage that does not prevent laser
Timepoint [2] 304093 0
at six months after randomisation
Secondary outcome [1] 340936 0
Change in classification of vitreous hemorrhage greater than 2 stages (according to the table below)


5- No vision of retina or optic disk
4- Optic disk view only
3- Vision of optic disk and large arcade vases, without conditions for photocoagulation
2- Vitreous hemorrhage located by quadrant with retinal and vases vision enough to make laser in 1-2 quadrants
1- Vitreous hemorrhage located by quadrant with retinal and vases vision enough to make laser in 3-4 quadrants
0- Peripheral vitreous hemorrhage that does not prevent laser

Timepoint [1] 340936 0
After six months of follow-up
Secondary outcome [2] 344828 0
Change in visual acuity (better corrected visual acuity more than or equal to 20/40) based on visual acuity test
Timepoint [2] 344828 0
After six months of follow-up

Eligibility
Key inclusion criteria
Diabetic patients Type 1 or type 2 with worsening of visual acuity (better corrected visual acuity less than or equal to 20/40) caused by vitreous hemorrhage with evolution without improvement of at least 30 days.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of tractional retinal detachment evidenced by ultrasound
Ocular inflammation or active infection (conjunctivitis, keratitis, swollen, scleritis, endophthalmitis)
Prior treatment with Antiangiogênico with less than 30 days
Vitrectomy via pars plane prior
Concomitant retinal disease that may interfere with the analysis of the final results ( macular hole, venous occlusion, AMD)
Known sensitivity to the drug used in the study

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The patients will be randomized as follows:
Sum of the patient's birth date: (dd + mm + yyyy)
-If the sum is a even number: Bevacizumabe injection
-If the sum is an odd number: simulated injection
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
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 outside Australia
Country [1] 9402 0
Brazil
State/province [1] 9402 0
São Paulo/Sorocaba

Funding & Sponsors
Funding source category [1] 298077 0
Hospital
Name [1] 298077 0
Hospital Oftalmológico de Sorocaba
Address [1] 298077 0
Rua Nabeck Shiroma 210, Sorocaba, SP, 18031-060
Country [1] 298077 0
Brazil
Primary sponsor type
Hospital
Name
Hospital Oftalmológico de Sorocaba
Address
Hospital Oftalmológico de Sorocaba - Rua Nabeck Shiroma 210, Sorocaba, SP, 18031-060
Country
Brazil
Secondary sponsor category [1] 297868 0
None
Name [1] 297868 0
Address [1] 297868 0
Country [1] 297868 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299099 0
88 - Hospital Oftalmológico de Sorocaba/SP
Ethics committee address [1] 299099 0
Rua Nabeck Shiroma, 210, Sorocaba-SP
Ethics committee country [1] 299099 0
Brazil
Date submitted for ethics approval [1] 299099 0
19/04/2017
Approval date [1] 299099 0
02/05/2017
Ethics approval number [1] 299099 0

Summary
Brief summary
The microvascular complications of diabetes mellitus in the retina, defined as diabetic retinopathy (RD), constitute one of the main causes of blindness of the economically active population in Brazil and the world. Macular edema is the main cause of low visual acuity, however the proliferative form of RD is that it relates more frequently to severe visual loss.

The presence of vitreous hemorrhage in patients with proliferative diabetic retinopathy is one of the main causes of severe visual acuity low in these patients.

Vitreous hemorrhage that evolves without spontaneous absorption can significantly affect visual rehabilitation and require additional surgical procedures for improvement of the vision.

The growth factor endothelial (VEGF) is expressed in high levels in the retina of diabetic retinopathy patients and are directly related to the formation of new vessels. By promoting a leukocyte migration and adhesion on the wall of vascular endothelial cells, increases vascular permeability and angiogenesis, with consequent progression of diabetic retinopathy.

Inhibition of vascular growth factor may induce proliferative diabetic retinopathy regression and combat the exuding phenomenon.

Bevacizumab (Avastin; Genentech, INC, South San Francisco, CA) is a monoclonal recombinant antibody against VEGF. Intravitreal injections of bevacizumab has been widely used in the treatment of different manifestations of proliferative diabetic retinopathy, such as progressive retinopathy active, before or combined with vitrectomy via pars plana (VVPP), severe retinal neovascularization or as a preoperative adjuvant to facilitate the surgery of VVPP.
The vitreous hemorrhage presents itself as an evolution of this rigged angiogenesis process.
The VVPP is the gold standard treatment for vitreous hemorrhage with or without tractional retinal detachment secondary proliferative diabetic retinopathy. Despite the VVPP having a high anatomical success rate, this procedure may be associated with surgery induced complications such as recurring vitreous hemorrhage, neovascular glaucoma, tractional retinal detachment and cataract. Such complications can compromise visual results. Moreover, a significant increase in the monetary cost of treatment.
Until the present moment, there are few works that aims to evaluate whether patients presenting vitreous hemorrhage without retinal detachment, when subjected to VEGF intravitreal injections, has higher rates of spontaneous reabsorption of hemorrhage with consequent reduction in the need for surgery indication.


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79282 0
Dr Arnaldo Furman Bordon
Address 79282 0
Hospital Oftalmológico de Sorocaba - Rua Nabeck Shiroma 210, Sorocaba, SP, 18031-060
Country 79282 0
Brazil
Phone 79282 0
+55011992982929
Fax 79282 0
Email 79282 0
afbordon@terra.com.br
Contact person for public queries
Name 79283 0
Dr Renata Guarischi Amaral Valentim
Address 79283 0
Hospital Oftalmológico de Sorocaba - Rua Nabeck Shiroma 210, Sorocaba, SP, 18031-060
Country 79283 0
Brazil
Phone 79283 0
+55011981196789
Fax 79283 0
Email 79283 0
re_guarischi@hotmail.com
Contact person for scientific queries
Name 79284 0
Dr Renata Guarischi Amaral Valentim
Address 79284 0
Hospital Oftalmológico de Sorocaba - Rua Nabeck Shiroma 210, Sorocaba, SP, 18031-060
Country 79284 0
Brazil
Phone 79284 0
+55011981196789
Fax 79284 0
Email 79284 0
re_guarischi@hotmail.com

No data has been provided for results reporting
Summary results
Not applicable