Corneal NeovascularizationPhase 2/3NCT00555594
Prospective Study to Determine the Effect of Subconjunctival Bevacizumab (AVASTIN) in Corneal Neovascularization
A Phase 2/3 study testing Bevacizumab (Avastin) in people with Corneal Neovascularization, run by Asociación para Evitar la Ceguera en México at 1 site in Mexico.
Trial summary
To determine the effect of subconjunctival Bevacizumab in corneal neovascularization Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corneal Neovascularization
- What is being tested?
- Bevacizumab (Avastin)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteMexico
- Study dates
- Sep 2006to Oct 2007
- Phase
- Phase 2/3
- 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
- Presence of vessels in minimum one quadrant
- vessels that penetrate more than 0.5 mm of the limb, in any depth
- who had signed the informed consent
- those that could attend to frequent ophthalmologic revisions after treatment and could wait for 6 months before the surgical procedure.
Who cannot join
- Patients with urgent need of a penetrating keratoplasty, pregnancy or lactancy
- Patient that may need an additional procedure to penetrating keratoplasty.
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Asociación Para Evitar la Ceguera en México, IAP, Hospital "Dr. Luis Sánchez Bulnes"
Mexico City, 04030
About this study
To determine the effect of subconjunctival Bevacizumab in corneal neovascularization
Read the detailed description
Corneal transplantation is the most commonly performed transplant surgery in the world today. Immunologic rejection is the leading cause of graft failure, with about 25% of graft recipients experiencing at least one episode of rejection. Of these episodes, about 20% are irreversible. The rate of corneal graft rejection in high-risk eyes, such as corneal neovascularization, has been reported to be 50% to 70%. Vascularized corneas have a much higher rate of graft rejection than avascular corneas. Whereas the normal cornea is devoid of blood and lymphatic vessels, both can invade the cornea secondary to a variety of corneal diseases and after surgery. This not only reduces visual acuity, but also renders such a cornea high-risk, if subsequent corneal transplantation is performed.Anti-angiogenesis, the pharmacologic inhibition of new blood vessel growth and formation, is a new treatment strategy under active and vigorous investigation. Multiple growth factors have been shown to contribute to the molecular events involved in the regulation of blood vessel growth Similarly, it is assumed that angiogenic growth factors such as vascular endothelial growth factor (VEGF), considered a major pro-angiogenic factor, could play a role in the pathogenesis of neovascularization.
Several approaches can be taken to neutralize VEGF. Bevacizumab (Avastin) is a full-length humanized murine monoclonal antibody against the VEGF molecule.It binds to and inhibits the biologic activity of human VEGF preventing the interaction of this molecule to its receptors on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new vessel formation.
There is evidence that triamcinolone acetonide (TA) inhibits vasogenic edema and inflammation, decreases vascular leakage, reduces the secretion of VEGF by pigment epithelial cells during oxidative stress and, down-regulates the expression of the VEGF gene in vascular smooth muscle cells Furthermore, TA decreases the paracellular permeability of cultured epithelial cells and down-regulates the inflammatory expression of endothelial adhesion molecules.
- Conditions
- Corneal Neovascularization
- Being tested
- Bevacizumab (Avastin)
- Keywords
- corneal neovascularization, Bevacizumab (Avastin), Immunologic rejection, vascular endothelial growth factor
- Medical subject headings
- Corneal Neovascularization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab (Avastin)Drug
One dose of 0.1cc of subconjunctival Bevacizumab was applied
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Patients with corneal neovascularization of infectious etiology, steroid reactors, and know glaucoma or glaucoma suspects. They received one dose of 0.1cc of subconjunctival Bevacizumab (Avastin™ Genentech, Inc, USA) in bulbar conjunctiva, 2 mm from the limbus, according to the location of the vessels. Receives: Drug: Bevacizumab (Avastin) |
| B | Active comparator | Patients with corneal neovascularization of any cause except for infectious disease. Patients of this group received one application of 0.1cc of subconjunctival Bevacizumab™ + 0.1cc of triamcinolone acetonide (ATLC; Grin laboratories, México city) in bulbar conjunctiva, 2 mm from de limbus, according to the location of the vessels. Receives: Drug: Bevacizumab (Avastin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anterior segment slit-lamp photographs and fluorescein angiograms Compared for any sign of diminished vascularization
Measured: three weeks after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2007 (estimated)
- Study startSep 2006
- Primary completionSep 2006
- Study completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Corneal NeovascularizationStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asociación para Evitar la Ceguera en México
- Sponsor type
- University, hospital or other
- Collaborators
- National Council of Science and Technology, Mexico, Universidad Nacional Autonoma de Mexico
- Investigators
- Hernández-Quintela Everardo, MD, Principal investigator, Consejo Nacional de Ciencia y Tecnología (CONACYT) grant no. 115755 (EHQ)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00555594
- Sponsor's protocol ID
- Cornea2
- Status last verified
- Jul 2024
- First submitted
- 7 Nov 2007
- Last updated
- 1 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Foulks GN, Sanfilippo FP, Locascio JA 3rd, MacQueen JM, Dawson DV. Histocompatibility testing for keratoplasty in high-risk patients. Ophthalmology. 1983 Mar;90(3):239-44. doi: 10.1016/s0161-6420(83)34575-9.
PubMed 6346199Cursiefen C, Seitz B, Dana MR, Streilein JW. [Angiogenesis and lymphangiogenesis in the cornea. Pathogenesis, clinical implications and treatment options]. Ophthalmologe. 2003 Apr;100(4):292-9. doi: 10.1007/s00347-003-0798-y. German.
PubMed 12682761Ciardella AP, Donsoff IM, Guyer DR, Adamis A, Yannuzzi LA. Antiangiogenesis agents. Ophthalmol Clin North Am. 2002 Dec;15(4):453-8. doi: 10.1016/s0896-1549(02)00042-1.
PubMed 12515077Foulks GN, Sanfilippo F. Beneficial effects of histocompatibility in high-risk corneal transplantation. Am J Ophthalmol. 1982 Nov;94(5):622-9. doi: 10.1016/0002-9394(82)90007-1.
PubMed 6756156Norrby K. In vivo models of angiogenesis. J Cell Mol Med. 2006 Jul-Sep;10(3):588-612. doi: 10.1111/j.1582-4934.2006.tb00423.x.
PubMed 16989723Kuwano M, Fukushi J, Okamoto M, Nishie A, Goto H, Ishibashi T, Ono M. Angiogenesis factors. Intern Med. 2001 Jul;40(7):565-72. doi: 10.2169/internalmedicine.40.565.
PubMed 11506294Kvanta A, Sarman S, Fagerholm P, Seregard S, Steen B. Expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in inflammation-associated corneal neovascularization. Exp Eye Res. 2000 Apr;70(4):419-28. doi: 10.1006/exer.1999.0790.
PubMed 10865990Gan L, Fagerholm P, Palmblad J. Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the regulation of corneal neovascularization and wound healing. Acta Ophthalmol Scand. 2004 Oct;82(5):557-63. doi: 10.1111/j.1600-0420.2004.00312.x.
PubMed 15453853Manzano RP, Peyman GA, Khan P, Carvounis PE, Kivilcim M, Ren M, Lake JC, Chevez-Barrios P. Inhibition of experimental corneal neovascularisation by bevacizumab (Avastin). Br J Ophthalmol. 2007 Jun;91(6):804-7. doi: 10.1136/bjo.2006.107912. Epub 2006 Dec 19.
PubMed 17179168Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997 Oct 15;57(20):4593-9.
PubMed 9377574
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study to Determine the Effect of Subconjunctival Bevacizumab (AVASTIN) in Corneal Neovascularization
- ClinicalTrials.gov ID
- NCT00555594
- Acronym / sponsor ID
- Cornea2
- Conditions
- Corneal Neovascularization
- Keywords
- corneal neovascularization, Bevacizumab (Avastin), Immunologic rejection, vascular endothelial growth factor
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Asociación para Evitar la Ceguera en MéxicoUniversity, hospital or other
- Collaborators
- National Council of Science and Technology, Mexico, Universidad Nacional Autonoma de Mexico
- Study start
- Sep 2006 (actual)
- Primary completion
- Sep 2006 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 8 Nov 2007 (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.
To determine the effect of subconjunctival Bevacizumab in corneal neovascularization
Detailed description
Corneal transplantation is the most commonly performed transplant surgery in the world today. Immunologic rejection is the leading cause of graft failure, with about 25% of graft recipients experiencing at least one episode of rejection. Of these episodes, about 20% are irreversible. The rate of corneal graft rejection in high-risk eyes, such as corneal neovascularization, has been reported to be 50% to 70%. Vascularized corneas have a much higher rate of graft rejection than avascular corneas. Whereas the normal cornea is devoid of blood and lymphatic vessels, both can invade the cornea secondary to a variety of corneal diseases and after surgery. This not only reduces visual acuity, but also renders such a cornea high-risk, if subsequent corneal transplantation is performed.Anti-angiogenesis, the pharmacologic inhibition of new blood vessel growth and formation, is a new treatment strategy under active and vigorous investigation. Multiple growth factors have been shown to contribute to the molecular events involved in the regulation of blood vessel growth Similarly, it is assumed that angiogenic growth factors such as vascular endothelial growth factor (VEGF), considered a major pro-angiogenic factor, could play a role in the pathogenesis of neovascularization.
Several approaches can be taken to neutralize VEGF. Bevacizumab (Avastin) is a full-length humanized murine monoclonal antibody against the VEGF molecule.It binds to and inhibits the biologic activity of human VEGF preventing the interaction of this molecule to its receptors on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new vessel formation.
There is evidence that triamcinolone acetonide (TA) inhibits vasogenic edema and inflammation, decreases vascular leakage, reduces the secretion of VEGF by pigment epithelial cells during oxidative stress and, down-regulates the expression of the VEGF gene in vascular smooth muscle cells Furthermore, TA decreases the paracellular permeability of cultured epithelial cells and down-regulates the inflammatory expression of endothelial adhesion molecules.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: Bevacizumab (Avastin)Patients with corneal neovascularization of infectious etiology, steroid reactors, and know glaucoma or glaucoma suspects. They received one dose of 0.1cc of subconjunctival Bevacizumab (Avastin™ Genentech, Inc, USA) in bulbar conjunctiva, 2 mm from the limbus, according to the location of the vessels. |
| B | Active comparator | Drug: Bevacizumab (Avastin)Patients with corneal neovascularization of any cause except for infectious disease. Patients of this group received one application of 0.1cc of subconjunctival Bevacizumab™ + 0.1cc of triamcinolone acetonide (ATLC; Grin laboratories, México city) in bulbar conjunctiva, 2 mm from de limbus, according to the location of the vessels. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Presence of vessels in minimum one quadrant
- vessels that penetrate more than 0.5 mm of the limb, in any depth
- who had signed the informed consent
- those that could attend to frequent ophthalmologic revisions after treatment and could wait for 6 months before the surgical procedure.
Key exclusion criteria (2 listed)
- Patients with urgent need of a penetrating keratoplasty, pregnancy or lactancy
- Patient that may need an additional procedure to penetrating keratoplasty.
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 |
|---|---|---|
| Bevacizumab (Avastin)One dose of 0.1cc of subconjunctival Bevacizumab was applied | Drug | A, B |
Primary outcome
Anterior segment slit-lamp photographs and fluorescein angiograms Compared for any sign of diminished vascularization
Time frame: three weeks after treatment
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 1 Aug 2024.
- Background: PubMed 6346199Foulks GN, Sanfilippo FP, Locascio JA 3rd, MacQueen JM, Dawson DV. Histocompatibility testing for keratoplasty in high-risk patients. Ophthalmology. 1983 Mar;90(3):239-44. doi: 10.1016/s0161-6420(83)34575-9.
- Background: PubMed 12682761Cursiefen C, Seitz B, Dana MR, Streilein JW. [Angiogenesis and lymphangiogenesis in the cornea. Pathogenesis, clinical implications and treatment options]. Ophthalmologe. 2003 Apr;100(4):292-9. doi: 10.1007/s00347-003-0798-y. German.
- Background: PubMed 12515077Ciardella AP, Donsoff IM, Guyer DR, Adamis A, Yannuzzi LA. Antiangiogenesis agents. Ophthalmol Clin North Am. 2002 Dec;15(4):453-8. doi: 10.1016/s0896-1549(02)00042-1.
- Background: PubMed 6756156Foulks GN, Sanfilippo F. Beneficial effects of histocompatibility in high-risk corneal transplantation. Am J Ophthalmol. 1982 Nov;94(5):622-9. doi: 10.1016/0002-9394(82)90007-1.
- Background: PubMed 16989723Norrby K. In vivo models of angiogenesis. J Cell Mol Med. 2006 Jul-Sep;10(3):588-612. doi: 10.1111/j.1582-4934.2006.tb00423.x.
- Background: PubMed 11506294Kuwano M, Fukushi J, Okamoto M, Nishie A, Goto H, Ishibashi T, Ono M. Angiogenesis factors. Intern Med. 2001 Jul;40(7):565-72. doi: 10.2169/internalmedicine.40.565.
- Background: PubMed 10865990Kvanta A, Sarman S, Fagerholm P, Seregard S, Steen B. Expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in inflammation-associated corneal neovascularization. Exp Eye Res. 2000 Apr;70(4):419-28. doi: 10.1006/exer.1999.0790.
- Background: PubMed 15453853Gan L, Fagerholm P, Palmblad J. Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the regulation of corneal neovascularization and wound healing. Acta Ophthalmol Scand. 2004 Oct;82(5):557-63. doi: 10.1111/j.1600-0420.2004.00312.x.
- Background: PubMed 17179168Manzano RP, Peyman GA, Khan P, Carvounis PE, Kivilcim M, Ren M, Lake JC, Chevez-Barrios P. Inhibition of experimental corneal neovascularisation by bevacizumab (Avastin). Br J Ophthalmol. 2007 Jun;91(6):804-7. doi: 10.1136/bjo.2006.107912. Epub 2006 Dec 19.
- Background: PubMed 9377574Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997 Oct 15;57(20):4593-9.
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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.
Hernández-Quintela Everardo, MD principal investigator
Consejo Nacional de Ciencia y Tecnología (CONACYT) grant no. 115755 (EHQ)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Bevacizumab (Avastin) in people with Corneal Neovascularization, run by Asociación para Evitar la Ceguera en México at 1 site in Mexico.
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 4 inclusion and 2 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 1 Aug 2024. 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 Mexico. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Anterior segment slit-lamp photographs and fluorescein angiograms Compared for any sign of diminished vascularization (time frame: three weeks after treatment). 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 NCT00555594, which also lists 10 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 1 Aug 2024.