Corneal NeovascularisationPhase 4NCT02594423
Strategies for Management of Corneal Neovascularisation
A Phase 4 study testing Fine Needle Diathermy and Bevacizumab in people with Corneal Neovascularisation, run by University of Nottingham.
Trial summary
The cornea is the transparent window of the eye, which allows light to enter into the eye and also contributes to the focusing of the light rays. One of the major factors responsible for its transparency is the lack of blood vessels. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corneal Neovascularisation
- What is being tested?
- Fine Needle Diathermy and Bevacizumab
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Dec 2015to Aug 2018
- Phase
- Phase 4
- 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
- Patients over the age of 18
- Able to give informed consent
- With corneal neovascularisation non responsive or not suitable for conventional steroid therapy
- Use of effective contraception in females of childbearing age
Who cannot join
- Patients under 18 years of age
- Patients unable or refusing to provide informed consent
- Patients who are needle phobic
- Pregnant women, women aiming for conception and breastfeeding women
- Patients with hypersensitivity to the active substance or to any of the excipients
- Patients with active or suspected ocular or periocular infections.
- Patients with active severe intraocular inflammation.
- Patients with raised intraocular pressure or on glaucoma medication
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Management of Active and Established Corneal Neovascularisation to Prevent Visual Impairment
The cornea is the transparent window of the eye, which allows light to enter into the eye and also contributes to the focusing of the light rays. One of the major factors responsible for its transparency is the lack of blood vessels. However, following inflammation new blood vessels (corneal vascularisation [CVas]) grow into the cornea affecting its transparency and impairing vision. CVas leads to further damage in the form of scarring,oedema,fat deposition and is a major cause of corneal graft rejection.
In 2000 with ethical approval (OY129801) the investigators developed and published a clinical technique called Fine Needle Diathermy occlusion of corneal vessels (FND). This has proven very successful for occluding established vessels and is practiced in many centers across the world. Recently it has been demonstrated that by inhibiting a chemical stimulant of vessel formation called vascular endothelial growth factor(VEGF) active new vessel growth in the retina can be suppressed. The approach is also being used for corneal new vessels. Bevacizumab (Avastin) is a chemical inhibitor of VEGF and is used extensively to treat retinal new vessels in macular degeneration. Avastin has been shown to be effective and safe in treating corneal new vessels. The investigators propose to evaluate the efficacy and safety of FND alone and FND combined with Avastin in treatment of CVas.
Read the detailed description
Corneal neovascularisation is a very common problem affecting both sexes at all ages and induced by differing underlying causes. It is considered to be the single most important risk factor for graft rejection. The process of angiogenesis, i.e. the formation of new blood vessels, is similar in any part of the body. Hence principles adopted to alleviate new blood vessels in one area can be applied to blood vessels in other areas using similar drugs.
Over the past 8 years a component necessary for angiogenesis, i.e Vascular endothelial growth factor (VEGF) has been targeted to induce regression of blood vessels in patients with cancer with an intravenous dosage of an anti-VEGF.
More recently, anti-VEGF therapies have targeted eye related neovascularisation, especially in the treatment of age related macular degeneration. This role has been expanded to include all other structures in the eye affected by angiogenesis such as neovascular glaucoma(Iris) and diabetic retinopathy(Retina).
Over the past few years attention has been drawn to the use of antiVEGF therapies to the surface of the eye. Many reports in international peer reviewed literature have commented on the use of anti VEGF therapy in the form of drops or injections on the surface of the eye, subconjunctivally and within the cornea. They have found drops and injections are safe, although injections appear to act more favourably. Avastin has been investigated for treating corneal new vessels and was proved to be both safe and effective.
Fine needle diathermy (FND) is a routine method for occluding corneal vessels that was developed in our department in 2000 and is used worldwide. It has been established that this technique is suitable for active and mature vessels.
However, the consequent transient tissue injury and inflammation can trigger further new vessel formation. Avastin is effective in occlusion of the active vessels only.It does not affect the established mature vessels. Hence if FND is combined with Avastin it is expected and hypothesized that a more efficient and lasting occlusion of vessels will be obtained. In this study, the investigators aim to investigate the combined action of Avastin and fine needle diathermy in occlusion of corneal vessels. The actual incidence of corneal neovascularisation in the UK is unknown but American studies suggest up to 1.4 million people are affected with sight threatening complications on annual basis. These blood vessels arise from a multitude of causes, including viral infections, corneal injuries, chronic inflammation and as a result of corneal transplantation. Conventional therapies at the present time include surgical occlusion of the blood vessels with a diathermy or laser or chronic use of steroids. The latter option is a associated with potential sight threatening complications such as glaucoma.
This study will generate data to inform further controlled studies towards establishing Avastin and fine needle diathermy as the treatment of choice for corneal new vessels.
- Conditions
- Corneal Neovascularisation
- Being tested
- Fine Needle Diathermy, Bevacizumab
- Medical subject headings
- Corneal Neovascularization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fine Needle DiathermyDevice
Fine needle diathermy is a surgical procedure that is used in the treatment of corneal NV. It is a safe and effective method for corneal vessels occlusion.
BevacizumabDrug
Also called Avastin(BEVACIZUMAB)
Bevacizumab is a humanized monoclonal antibody that binds to isoforms of VEGF-A .
| Study group | Role | What they receive |
|---|---|---|
| Fine needle Diathermy | Active comparator | Fine needle Diathermy(FND) will be applied under topical anaesthesia under an operating microscope. This involves the insertion of a fine corneal suture needle in the vicinity of the vessels and using this as an extension of the probe of a monopolar cautery to deliver the energy in the corneal tissue at the site at which it is required to occlude the vessels. Receives: Device: Fine Needle Diathermy |
| Fine Needle Diathermy and Bevacizumab | Active comparator | Fine needle Diathermy(FND) will be applied under topical anaesthesia under an operating microscope. This involves the insertion of a fine corneal suture needle in the vicinity of the vessels and using this as an extension of the probe of a monopolar cautery to deliver the energy in the corneal tissue at the site at which it is required to occlude the vessels. Patients will receive subconjunctival injections of bevacizumab in the conjunctiva near the limbus in the quadrant(s) affected (total volume of between 0.2 ml-0.3 ml of the 2.5 mg/0.1 ml solution). The subconjunctival injections will be administered after FND in the same treated quadrants. Receives: Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decreased corneal neovascularisation
A comparison of total vascularisation of the corneal area as measured by our grading system (Faraj LA et al, 2015) before and after treatment.
Measured: 6 months
Secondary outcomes (3)
Improved/maintained Snellen's visual acuity
Visual acuity is assessed using Snellen chart and vision is expressed in LOGMAR units
Measured: 10 months
Decreased corneal opacity related to lipid deposition
The response to treatment will be judged clinically by biomicroscopy examination and quantitatively by comparison with pre-treatment slit lamp photographs. The comparison of the pre and post treatment slit lamp images will be done by two independent blind reviewers.
Measured: 10 months
Reduced episodes of graft rejection(in corneal graft patients)
Number of rejection episodes will be recorded
Measured: 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study startDec 2015
- Primary completionAug 2017 (estimated)
- Study completionAug 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Corneal NeovascularisationStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Harminder S Dua, Professor, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02594423
- Sponsor's protocol ID
- 15070
- Other IDs
- 2015-003180-11, 2015
- Status last verified
- Dec 2015
- First submitted
- 27 Oct 2015
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Management of Active and Established Corneal Neovascularisation to Prevent Visual Impairment
- ClinicalTrials.gov ID
- NCT02594423
- Acronym / sponsor ID
- 15070
- Conditions
- Corneal Neovascularisation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Dec 2015
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Aug 2018 (estimated)
- First posted
- 3 Nov 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.
The cornea is the transparent window of the eye, which allows light to enter into the eye and also contributes to the focusing of the light rays. One of the major factors responsible for its transparency is the lack of blood vessels. However, following inflammation new blood vessels (corneal vascularisation [CVas]) grow into the cornea affecting its transparency and impairing vision. CVas leads to further damage in the form of scarring,oedema,fat deposition and is a major cause of corneal graft rejection.
In 2000 with ethical approval (OY129801) the investigators developed and published a clinical technique called Fine Needle Diathermy occlusion of corneal vessels (FND). This has proven very successful for occluding established vessels and is practiced in many centers across the world. Recently it has been demonstrated that by inhibiting a chemical stimulant of vessel formation called vascular endothelial growth factor(VEGF) active new vessel growth in the retina can be suppressed. The approach is also being used for corneal new vessels. Bevacizumab (Avastin) is a chemical inhibitor of VEGF and is used extensively to treat retinal new vessels in macular degeneration. Avastin has been shown to be effective and safe in treating corneal new vessels. The investigators propose to evaluate the efficacy and safety of FND alone and FND combined with Avastin in treatment of CVas.
Detailed description
Corneal neovascularisation is a very common problem affecting both sexes at all ages and induced by differing underlying causes. It is considered to be the single most important risk factor for graft rejection. The process of angiogenesis, i.e. the formation of new blood vessels, is similar in any part of the body. Hence principles adopted to alleviate new blood vessels in one area can be applied to blood vessels in other areas using similar drugs.
Over the past 8 years a component necessary for angiogenesis, i.e Vascular endothelial growth factor (VEGF) has been targeted to induce regression of blood vessels in patients with cancer with an intravenous dosage of an anti-VEGF.
More recently, anti-VEGF therapies have targeted eye related neovascularisation, especially in the treatment of age related macular degeneration. This role has been expanded to include all other structures in the eye affected by angiogenesis such as neovascular glaucoma(Iris) and diabetic retinopathy(Retina).
Over the past few years attention has been drawn to the use of antiVEGF therapies to the surface of the eye. Many reports in international peer reviewed literature have commented on the use of anti VEGF therapy in the form of drops or injections on the surface of the eye, subconjunctivally and within the cornea. They have found drops and injections are safe, although injections appear to act more favourably. Avastin has been investigated for treating corneal new vessels and was proved to be both safe and effective.
Fine needle diathermy (FND) is a routine method for occluding corneal vessels that was developed in our department in 2000 and is used worldwide. It has been established that this technique is suitable for active and mature vessels.
However, the consequent transient tissue injury and inflammation can trigger further new vessel formation. Avastin is effective in occlusion of the active vessels only.It does not affect the established mature vessels. Hence if FND is combined with Avastin it is expected and hypothesized that a more efficient and lasting occlusion of vessels will be obtained. In this study, the investigators aim to investigate the combined action of Avastin and fine needle diathermy in occlusion of corneal vessels. The actual incidence of corneal neovascularisation in the UK is unknown but American studies suggest up to 1.4 million people are affected with sight threatening complications on annual basis. These blood vessels arise from a multitude of causes, including viral infections, corneal injuries, chronic inflammation and as a result of corneal transplantation. Conventional therapies at the present time include surgical occlusion of the blood vessels with a diathermy or laser or chronic use of steroids. The latter option is a associated with potential sight threatening complications such as glaucoma.
This study will generate data to inform further controlled studies towards establishing Avastin and fine needle diathermy as the treatment of choice for corneal new vessels.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fine needle Diathermy | Active comparator | Device: Fine Needle DiathermyFine needle Diathermy(FND) will be applied under topical anaesthesia under an operating microscope. This involves the insertion of a fine corneal suture needle in the vicinity of the vessels and using this as an extension of the probe of a monopolar cautery to deliver the energy in the corneal tissue at the site at which it is required to occlude the vessels. |
| Fine Needle Diathermy and Bevacizumab | Active comparator | Drug: BevacizumabFine needle Diathermy(FND) will be applied under topical anaesthesia under an operating microscope. This involves the insertion of a fine corneal suture needle in the vicinity of the vessels and using this as an extension of the probe of a monopolar cautery to deliver the energy in the corneal tissue at the site at which it is required to occlude the vessels. Patients will receive subconjunctival injections of bevacizumab in the conjunctiva near the limbus in the quadrant(s) affected (total volume of between 0.2 ml-0.3 ml of the 2.5 mg/0.1 ml solution). The subconjunctival injections will be administered after FND in the same treated quadrants. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients over the age of 18
- Able to give informed consent
- With corneal neovascularisation non responsive or not suitable for conventional steroid therapy
- Use of effective contraception in females of childbearing age
Key exclusion criteria (8 listed)
- Patients under 18 years of age
- Patients unable or refusing to provide informed consent
- Patients who are needle phobic
- Pregnant women, women aiming for conception and breastfeeding women
- Patients with hypersensitivity to the active substance or to any of the excipients
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 |
|---|---|---|
| Fine Needle DiathermyFine needle diathermy is a surgical procedure that is used in the treatment of corneal NV. It is a safe and effective method for corneal vessels occlusion. | Device | Fine needle Diathermy |
| BevacizumabAlso: Avastin(BEVACIZUMAB)Bevacizumab is a humanized monoclonal antibody that binds to isoforms of VEGF-A . | Drug | Fine Needle Diathermy and Bevacizumab |
Primary outcome
Decreased corneal neovascularisation
Time frame: 6 months
A comparison of total vascularisation of the corneal area as measured by our grading system (Faraj LA et al, 2015) before and after treatment.
3 secondary outcomes
Improved/maintained Snellen's visual acuity
Time frame: 10 months
Decreased corneal opacity related to lipid deposition
Time frame: 10 months
Reduced episodes of graft rejection(in corneal graft patients)
Time frame: 10 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
Related trials for Corneal Neovascularisation
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Fine-needle Diathermy Combined With Subconjunctival Bevacizumab for Corneal Neovascularization
Corneal Neovascularisation
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Clinical Study of Intrastromal Anti-VEGF Injection for Corneal Neovascularization.
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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.
Harminder S Dua, Professor principal investigator
University of Nottingham
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fine Needle Diathermy and Bevacizumab in people with Corneal Neovascularisation, run by University of Nottingham.
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 8 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: status not confirmed, as of the sponsor's last update on 2 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Harminder S Dua, Professor (+44 (0) 115970 9796, harminder.dua@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decreased corneal neovascularisation (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Dec 2015.