Diabetic Macular EdemaNCT02556723
Intravitreal Injections of Ziv-aflibercept for Macular Diseases
A study testing Intravitreal injections of ziv-aflibercept in people with Diabetic Macular Edema and Age Related Macular Degeneration, run by Retina Clinic, Sao Paulo, Brazil at 1 site in Brazil.
Trial summary
Diabetic macular edema (DME), wet-AMD and macular edema secondary to vein occlusions are the leading cause of blindness in developed countries. Several therapies have been studied as such laser treatment and intravitreal injections of corticosteroids or anti-VEGF drugs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema, Age Related Macular Degeneration, Branch Retinal Vein Occlusion With Macular Edema
- What is being tested?
- Intravitreal injections of ziv-aflibercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteBrazil
- Study dates
- Sep 2014to Sep 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥ 18 years with type 1 or 2 diabetes mellitus
- BCVA varying from 20/62 to 20/400 (Snellen chart) - equivalent 0.49 to 1.30 logMAR - caused by DME
- Central Retinal Thickness on OCT (Heildelberg Engineering, Heidelberg, Germany ) of 275 mm or more
Who cannot join
- Laser photocoagulation within the previous 6 months
- Previous intraocular anti-VEGF or corticosteroid injection
- Previous systemic anti-VEGF or receptor tyrosine kinase inhibitor therapy
- Vitreomacular traction or epiretinal membrane producing any traction on the macula on SD-OCT scan
- Angiographic evidence of macular ischemia defined as foveal avascular zone greatest linear dimension of more than 1000 mm or severe perifoveal capillary loss
- Previous cataract, trabeculectomy or vitrectomy
Show all 16Show fewer
- Aphakia
- External ocular infections
- Glaucoma (IOP of > 21 mmHg or regular use of more than 2 IOP lowering drugs)
- Likelihood of needing intraocular surgery within 6 months
- Proliferative diabetic retinopathy with any evidence of retinal traction
- Systemic conditions that precluded trial enrollment included glycosylated hemoglobin of more than 10.0%
- Past medical history of chronic renal failure requiring either dialysis or kidney transplantation
- Blood pressure of more than 160/90 mmHg
- an arteriothrombotic event within 6 months before randomization, including myocardial infarction, acute congestive heart failure or other cardiac event, and stroke or transient ischemic attack
- Pregnancy or breastfeeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intravitreal Injections of Ziv-aflibercept for Macular Diseases: Diabetic Macular Edema, Wet AMD and Macular Edema Secondary to Vein Occlusons
Diabetic macular edema (DME), wet-AMD and macular edema secondary to vein occlusions are the leading cause of blindness in developed countries. Several therapies have been studied as such laser treatment and intravitreal injections of corticosteroids or anti-VEGF drugs. In terms of public health the long term treatment with the current available drugs is very expensive and new therapies with the same or better effect should be investigated. This study intends to evaluate the efficacy and safety of intravitreal injections of ziv-aflibercept for the treatment of patients with DME, wet-AMD and macular edema secondary to vein occlusions.
Read the detailed description
Twenty consecutive patients with DME, wet-AMD and macular edema secondary to vein occlusions will be enrolled. A complete examination including full-field ERG, visual acuity, central retinal thickness (CRT) and evaluation of systemic and ocular complications will be performed before and 24 weeks after intravitreal injections of ziv-aflibercept. The twenty patients will be submitted to 6 consecutive intravitreal injections of ziv-aflibercept with a 4 week interval.
The safety and efficacy of Eylea in the treatment of macular edema following CRVO were assessed in 2 randomized, multicenter, double- masked, sham-controlled studies: COPERNICUS and GALILEO. A total of 358 patients were treated and evaluable for efficacy (217 with Eylea) in the two studies. In both, patients were randomly assigned in a 3:2 ratio to either 2 mg Eylea administered every 4 weeks, or sham injections (control group) administered every 4 weeks for a total of 6 injections. After 6 monthly injections, patients continued to receive Eylea treatment during weeks 24 to 52 only if they met pre-specified retreatment criteria (PRN), except for patients in the sham control group in the GALILEO study who continued to receive sham injections through week 52. In the COPERNICUS study, after 6 months, 56% of patients receiving Eylea 2 mg monthly gained at least 15 letters of BCVA from baseline, as measured by ETDRS, compared to 12% of patients receiving sham injections (p<0.01), the primary endpoint of the study. Patients receiving Eylea 2 mg monthly gained, on average, 17.3 letters of vision compared to a mean loss of 4.0 letters with sham control injections (p<0.01), a secondary endpoint.
Ziv-aflibercept or zaltrap6 (Sanofi-Aventis US, LLC, Bridgewater, NJ/Regeneron Pharmaceuticals, Inc, Tarrytown, NY) is FDA approved for the treatment of metastatic colorectal cancer. During Bascom Palmer Eye Institute's Angiogenesis, Exudation, and Degeneration February 2014 conference, Michel Eid Farah, João R. Dias, Fernando M. Penha, and Eduardo B. Rodrigues investigated the safety of ziv-aflibercept in vitro and in vivo. In vitro toxicity was verified using ARPE-19 cultured cells exposed to anti-angiogenic vs balanced salt solution (BSS) for 10 minutes. Viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which evaluates cell viability by mitochondrial activity. No signs of cell toxicity were observed, and cell viability was similar for ziv-aflibercept, aflibercept, and BSS. For the in vivo study, they tested 1 injection of 0.05 mL ziv-aflibercept vs aflibercept in the right eyes of 18 rabbits, 9 eyes in each group. BSS was injected in the fellow eyes and served as control. After the injections, all animals were examined by funduscopy, SD-OCT), and ERG at baseline, 24 hours, and 7 days. Aqueous, vitreous, and serum samples were collected at baseline, 24 hours, and 7 days for pH and osmolarity analysis. The animals were sacrificed and the eyes were enucleated for morphologic study by light and electron microscopy. No abnormalities were found at 24 hours or 7 days after intravitreal injection of either drug when assessed by fundus exam and SD-OCT, ERG, and histology as well as transmission microscopy. There were also no changes in osmolarity in the aqueous humor or vitreous samples in any group after 24 hours and 1 week.
- Conditions
- Diabetic Macular Edema, Age Related Macular Degeneration, Branch Retinal Vein Occlusion With Macular Edema, Central Retinal Vein Occlusion With Macular Edema
- Being tested
- Intravitreal injections of ziv-aflibercept
- Medical subject headings
- Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravitreal injections of ziv-afliberceptDrug
Also called Intravitreal injections of Zaltrap
All subjects will receive intravitreal injections of ziv-aflibercept under sterile conditions at baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 20 weeks. No topical or systemic antibiotics will be prescribed (pre- injection or postinjection).
| Study group | Role | What they receive |
|---|---|---|
| Ziv-aflibercept IV | Experimental | All subjects will receive intravitreal injections of ziv-aflibercept under sterile conditions at baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 20 weeks. Receives: Drug: Intravitreal injections of ziv-aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multifocal electroretinogram responses at Week 24 and 48
Measured: 24 and 48 weeks
Secondary outcomes (2)
Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Snellen Letter Score at Week 24 and 48
Measured: 24 and 48 weeks
Change From Baseline in Central Retinal Thickness (CRT) at Week 24 and 48 as Assessed on Optical Coherence Tomography (OCT)
Measured: 24 and 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2015 (estimated)
- Study startSep 2014
- Primary completionSep 2015
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Retina Clinic, Sao Paulo, Brazil
- Sponsor type
- University, hospital or other
- Collaborators
- Federal University of São Paulo
- Responsible party
- Sponsor
- Investigators
- André Maia, M.D., Study director, C.E.O.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02556723
- Sponsor's protocol ID
- RetinaCLINIC
- Status last verified
- Oct 2016
- First submitted
- 18 Sep 2015
- Last updated
- 4 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007. Epub 2009 Nov 6.
PubMed 19896746Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes. Ophthalmology. 2009 Mar;116(3):497-503. doi: 10.1016/j.ophtha.2008.10.016. Epub 2009 Jan 22.
PubMed 19167079Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.
PubMed 8366922Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53.
PubMed 9742976Gray A, Clarke P, Farmer A, Holman R; United Kingdom Prospective Diabetes Study (UKPDS) Group. Implementing intensive control of blood glucose concentration and blood pressure in type 2 diabetes in England: cost analysis (UKPDS 63). BMJ. 2002 Oct 19;325(7369):860. doi: 10.1136/bmj.325.7369.860.
PubMed 12386035Stratton IM, Cull CA, Adler AI, Matthews DR, Neil HA, Holman RR. Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia. 2006 Aug;49(8):1761-9. doi: 10.1007/s00125-006-0297-1. Epub 2006 May 31.
PubMed 16736131Ishida S, Usui T, Yamashiro K, Kaji Y, Ahmed E, Carrasquillo KG, Amano S, Hida T, Oguchi Y, Adamis AP. VEGF164 is proinflammatory in the diabetic retina. Invest Ophthalmol Vis Sci. 2003 May;44(5):2155-62. doi: 10.1167/iovs.02-0807.
PubMed 12714656Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004 Aug;25(4):581-611. doi: 10.1210/er.2003-0027.
PubMed 15294883Cunningham ET Jr, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ, Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD; Macugen Diabetic Retinopathy Study Group. A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology. 2005 Oct;112(10):1747-57. doi: 10.1016/j.ophtha.2005.06.007.
PubMed 16154196Arevalo JF, Sanchez JG, Fromow-Guerra J, Wu L, Berrocal MH, Farah ME, Cardillo J, Rodriguez FJ; Pan-American Collaborative Retina Study Group (PACORES). Comparison of two doses of primary intravitreal bevacizumab (Avastin) for diffuse diabetic macular edema: results from the Pan-American Collaborative Retina Study Group (PACORES) at 12-month follow-up. Graefes Arch Clin Exp Ophthalmol. 2009 Jun;247(6):735-43. doi: 10.1007/s00417-008-1034-x. Epub 2009 Feb 3.
PubMed 19189118Nguyen QD, Shah SM, Khwaja AA, Channa R, Hatef E, Do DV, Boyer D, Heier JS, Abraham P, Thach AB, Lit ES, Foster BS, Kruger E, Dugel P, Chang T, Das A, Ciulla TA, Pollack JS, Lim JI, Eliott D, Campochiaro PA; READ-2 Study Group. Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology. 2010 Nov;117(11):2146-51. doi: 10.1016/j.ophtha.2010.08.016. Epub 2010 Sep 19.
PubMed 20855114Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801. doi: 10.1016/j.ophtha.2011.12.039. Epub 2012 Feb 11.
PubMed 22330964Do DV, Schmidt-Erfurth U, Gonzalez VH, Gordon CM, Tolentino M, Berliner AJ, Vitti R, Ruckert R, Sandbrink R, Stein D, Yang K, Beckmann K, Heier JS. The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology. 2011 Sep;118(9):1819-26. doi: 10.1016/j.ophtha.2011.02.018. Epub 2011 May 5.
PubMed 21546089Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11393-8. doi: 10.1073/pnas.172398299. Epub 2002 Aug 12.
PubMed 12177445de Oliveira Dias JR, Badaro E, Novais EA, Colicchio D, Chiarantin GM, Matioli MM, Verna C, Penha FM, Barros NM, Meyer CH, Farah ME, Rodrigues EB. Preclinical investigations of intravitreal ziv-aflibercept. Ophthalmic Surg Lasers Imaging Retina. 2014 Nov-Dec;45(6):577-84. doi: 10.3928/23258160-20141118-15.
PubMed 25423640
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravitreal Injections of Ziv-aflibercept for Macular Diseases: Diabetic Macular Edema, Wet AMD and Macular Edema Secondary to Vein Occlusons
- ClinicalTrials.gov ID
- NCT02556723
- Acronym / sponsor ID
- RetinaCLINIC
- Conditions
- Diabetic Macular Edema, Age Related Macular Degeneration, Branch Retinal Vein Occlusion With Macular Edema, Central Retinal Vein Occlusion With Macular Edema
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Retina Clinic, Sao Paulo, BrazilUniversity, hospital or other
- Collaborators
- Federal University of São Paulo
- Study start
- Sep 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 22 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diabetic macular edema (DME), wet-AMD and macular edema secondary to vein occlusions are the leading cause of blindness in developed countries. Several therapies have been studied as such laser treatment and intravitreal injections of corticosteroids or anti-VEGF drugs. In terms of public health the long term treatment with the current available drugs is very expensive and new therapies with the same or better effect should be investigated. This study intends to evaluate the efficacy and safety of intravitreal injections of ziv-aflibercept for the treatment of patients with DME, wet-AMD and macular edema secondary to vein occlusions.
Detailed description
Twenty consecutive patients with DME, wet-AMD and macular edema secondary to vein occlusions will be enrolled. A complete examination including full-field ERG, visual acuity, central retinal thickness (CRT) and evaluation of systemic and ocular complications will be performed before and 24 weeks after intravitreal injections of ziv-aflibercept. The twenty patients will be submitted to 6 consecutive intravitreal injections of ziv-aflibercept with a 4 week interval.
The safety and efficacy of Eylea in the treatment of macular edema following CRVO were assessed in 2 randomized, multicenter, double- masked, sham-controlled studies: COPERNICUS and GALILEO. A total of 358 patients were treated and evaluable for efficacy (217 with Eylea) in the two studies. In both, patients were randomly assigned in a 3:2 ratio to either 2 mg Eylea administered every 4 weeks, or sham injections (control group) administered every 4 weeks for a total of 6 injections. After 6 monthly injections, patients continued to receive Eylea treatment during weeks 24 to 52 only if they met pre-specified retreatment criteria (PRN), except for patients in the sham control group in the GALILEO study who continued to receive sham injections through week 52. In the COPERNICUS study, after 6 months, 56% of patients receiving Eylea 2 mg monthly gained at least 15 letters of BCVA from baseline, as measured by ETDRS, compared to 12% of patients receiving sham injections (p<0.01), the primary endpoint of the study. Patients receiving Eylea 2 mg monthly gained, on average, 17.3 letters of vision compared to a mean loss of 4.0 letters with sham control injections (p<0.01), a secondary endpoint.
Ziv-aflibercept or zaltrap6 (Sanofi-Aventis US, LLC, Bridgewater, NJ/Regeneron Pharmaceuticals, Inc, Tarrytown, NY) is FDA approved for the treatment of metastatic colorectal cancer. During Bascom Palmer Eye Institute's Angiogenesis, Exudation, and Degeneration February 2014 conference, Michel Eid Farah, João R. Dias, Fernando M. Penha, and Eduardo B. Rodrigues investigated the safety of ziv-aflibercept in vitro and in vivo. In vitro toxicity was verified using ARPE-19 cultured cells exposed to anti-angiogenic vs balanced salt solution (BSS) for 10 minutes. Viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which evaluates cell viability by mitochondrial activity. No signs of cell toxicity were observed, and cell viability was similar for ziv-aflibercept, aflibercept, and BSS. For the in vivo study, they tested 1 injection of 0.05 mL ziv-aflibercept vs aflibercept in the right eyes of 18 rabbits, 9 eyes in each group. BSS was injected in the fellow eyes and served as control. After the injections, all animals were examined by funduscopy, SD-OCT), and ERG at baseline, 24 hours, and 7 days. Aqueous, vitreous, and serum samples were collected at baseline, 24 hours, and 7 days for pH and osmolarity analysis. The animals were sacrificed and the eyes were enucleated for morphologic study by light and electron microscopy. No abnormalities were found at 24 hours or 7 days after intravitreal injection of either drug when assessed by fundus exam and SD-OCT, ERG, and histology as well as transmission microscopy. There were also no changes in osmolarity in the aqueous humor or vitreous samples in any group after 24 hours and 1 week.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ziv-aflibercept IV | Experimental | Drug: Intravitreal injections of ziv-afliberceptAll subjects will receive intravitreal injections of ziv-aflibercept under sterile conditions at baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 20 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults ≥ 18 years with type 1 or 2 diabetes mellitus
- BCVA varying from 20/62 to 20/400 (Snellen chart) - equivalent 0.49 to 1.30 logMAR - caused by DME
- Central Retinal Thickness on OCT (Heildelberg Engineering, Heidelberg, Germany ) of 275 mm or more
Key exclusion criteria (16 listed)
- Laser photocoagulation within the previous 6 months
- Previous intraocular anti-VEGF or corticosteroid injection
- Previous systemic anti-VEGF or receptor tyrosine kinase inhibitor therapy
- Vitreomacular traction or epiretinal membrane producing any traction on the macula on SD-OCT scan
- Angiographic evidence of macular ischemia defined as foveal avascular zone greatest linear dimension of more than 1000 mm or severe perifoveal capillary loss
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravitreal injections of ziv-afliberceptAlso: Intravitreal injections of ZaltrapAll subjects will receive intravitreal injections of ziv-aflibercept under sterile conditions at baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 20 weeks. No topical or systemic antibiotics will be prescribed (pre- injection or postinjection). | Drug | Ziv-aflibercept IV |
Primary outcome
Multifocal electroretinogram responses at Week 24 and 48
Time frame: 24 and 48 weeks
2 secondary outcomes
Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Snellen Letter Score at Week 24 and 48
Time frame: 24 and 48 weeks
Change From Baseline in Central Retinal Thickness (CRT) at Week 24 and 48 as Assessed on Optical Coherence Tomography (OCT)
Time frame: 24 and 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2016.
- Results publication: PubMed 19896746Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007. Epub 2009 Nov 6.
- Results publication: PubMed 19167079Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes. Ophthalmology. 2009 Mar;116(3):497-503. doi: 10.1016/j.ophtha.2008.10.016. Epub 2009 Jan 22.
- Results publication: PubMed 8366922Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.
- Results publication: PubMed 9742976Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53.
- Results publication: PubMed 12386035Gray A, Clarke P, Farmer A, Holman R; United Kingdom Prospective Diabetes Study (UKPDS) Group. Implementing intensive control of blood glucose concentration and blood pressure in type 2 diabetes in England: cost analysis (UKPDS 63). BMJ. 2002 Oct 19;325(7369):860. doi: 10.1136/bmj.325.7369.860.
- Results publication: PubMed 16736131Stratton IM, Cull CA, Adler AI, Matthews DR, Neil HA, Holman RR. Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia. 2006 Aug;49(8):1761-9. doi: 10.1007/s00125-006-0297-1. Epub 2006 May 31.
- Results publication: PubMed 12714656Ishida S, Usui T, Yamashiro K, Kaji Y, Ahmed E, Carrasquillo KG, Amano S, Hida T, Oguchi Y, Adamis AP. VEGF164 is proinflammatory in the diabetic retina. Invest Ophthalmol Vis Sci. 2003 May;44(5):2155-62. doi: 10.1167/iovs.02-0807.
- Results publication: PubMed 15294883Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004 Aug;25(4):581-611. doi: 10.1210/er.2003-0027.
- Results publication: PubMed 16154196Cunningham ET Jr, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ, Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD; Macugen Diabetic Retinopathy Study Group. A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology. 2005 Oct;112(10):1747-57. doi: 10.1016/j.ophtha.2005.06.007.
- Results publication: PubMed 19189118Arevalo JF, Sanchez JG, Fromow-Guerra J, Wu L, Berrocal MH, Farah ME, Cardillo J, Rodriguez FJ; Pan-American Collaborative Retina Study Group (PACORES). Comparison of two doses of primary intravitreal bevacizumab (Avastin) for diffuse diabetic macular edema: results from the Pan-American Collaborative Retina Study Group (PACORES) at 12-month follow-up. Graefes Arch Clin Exp Ophthalmol. 2009 Jun;247(6):735-43. doi: 10.1007/s00417-008-1034-x. Epub 2009 Feb 3.
- Results publication: PubMed 20855114Nguyen QD, Shah SM, Khwaja AA, Channa R, Hatef E, Do DV, Boyer D, Heier JS, Abraham P, Thach AB, Lit ES, Foster BS, Kruger E, Dugel P, Chang T, Das A, Ciulla TA, Pollack JS, Lim JI, Eliott D, Campochiaro PA; READ-2 Study Group. Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology. 2010 Nov;117(11):2146-51. doi: 10.1016/j.ophtha.2010.08.016. Epub 2010 Sep 19.
- Results publication: PubMed 22330964Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801. doi: 10.1016/j.ophtha.2011.12.039. Epub 2012 Feb 11.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
André Maia, M.D. study director
C.E.O.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intravitreal injections of ziv-aflibercept in people with Diabetic Macular Edema and Age Related Macular Degeneration, run by Retina Clinic, Sao Paulo, Brazil at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Multifocal electroretinogram responses at Week 24 and 48 (time frame: 24 and 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02556723, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2016.