Corneal NeovascularizationPhase 1/2NCT01996826
A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
A Phase 1/2 study testing Avastin® (bevacizumab) and 0.9% NaCl & Refresh Liquigel in people with Corneal Neovascularization and Corneal Graft Failure, run by Reza Dana, MD at 3 sites in United States.
Trial summary
The goal of this study is to investigate whether using bevacizumab (Avastin®) is both safe and effective at decreasing the likelihood of a high-risk corneal graft rejection. Patients who are "high-risk" for rejection have blood vessels growing from the white of the eye into the cornea (clear, front region of the eye). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corneal Neovascularization, Corneal Graft Failure
- What is being tested?
- Avastin® (bevacizumab) and 0.9% NaCl & Refresh Liquigel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2014to Apr 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age > 18 years
- Participant willing and able to provide written informed consent
- Willing and able to comply with study assessments for the full duration of the study
- High-risk characteristics for penetrating keratoplasty:
- Presence of corneal NV in one or more quadrants (≥ 3 clock hours NV ≥ 2mm from the limbus) OR
- Extension of corneal NV to graft-host junction in a previous failed graft
- In generally good stable overall health
Who cannot join
- History of Stevens-Johnson syndrome or ocular pemphigoid
- Ocular or periocular malignancy
- Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
- Uncontrolled glaucoma
- Currently on dialysis
- Has received treatment with anti-VEGF agents (intraocular or systemic) within 45 days of study entry
Show all 14Show fewer
- Concurrent use of systemic anti-VEGF agents
- Change in topical corticosteroid regimen within 14 days of transplantation
- Use of systemic immunosuppressive for indication other than corneal graft rejection
- Pregnancy (positive pregnancy test) or lactating
- Pre-menopausal women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method)
- Uncontrolled hypertension defined as systolic blood pressure (BP) ≥150 or diastolic BP ≥90 mmHg
- History of thromboembolic event within 12 months prior to study entry
- Participation in another simultaneous medical investigation or trial
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
Bascom Palmer Eye Institute
Miami, Florida, 33136
New York Presbyterian Hospital
New York, New York, 10065
About this study
The goal of this study is to investigate whether using bevacizumab (Avastin®) is both safe and effective at decreasing the likelihood of a high-risk corneal graft rejection. Patients who are "high-risk" for rejection have blood vessels growing from the white of the eye into the cornea (clear, front region of the eye). The medication is used at the time of surgery and in the weeks following surgery. Participants have a 50/50 chance at receiving the active study medication or a placebo medication.
Read the detailed description
The purpose of this study is to test the effectiveness of a drug, bevacizumab (Avastin), in preventing blood vessels that often occur after a corneal transplantation which are considered at "high-risk" for rejection. In many cases these blood vessels lead to the graft rejection and eventual failure of the corneal transplant. It is hoped that this treatment will increase the chances of corneal graft survival.
The medication used in this study is called bevacizumab or Avastin (Genentech, Inc). It works by inhibiting the action of a molecule called vascular endothelial growth factor (VEGF). VEGF is a substance molecule that binds to certain cells to stimulate new blood vessel formation. When VEGF is bound to the drug, it cannot stimulate the formation and growth of new blood vessels. Growth of blood vessels into the cornea is a complication which can worsen the prognosis of your corneal transplant and put the transplant at a higher risk for rejection.
- Conditions
- Corneal Neovascularization, Corneal Graft Failure
- Being tested
- Avastin® (bevacizumab), 0.9% NaCl & Refresh Liquigel
- Keywords
- Corneal Neovascularization, Cornea Blood Vessels, Corneal Graft Failure, High-Risk Penetrating Keratoplasty, Corneal Transplant
- Medical subject headings
- Corneal Neovascularization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Avastin® (bevacizumab)Drug
Also called Avastin®, bevacizumab
One time subconjunctival injection of 0.1 mL (2.5 mg) bevacizumab followed by topical treatment with 1% solution bevacizumab four times a day for four weeks.
0.9% NaCl & Refresh LiquigelDrug
Also called Sodium Chloride, Refresh Liquigel, NaCL
One-time subconjunctival injection of 0.1mL 0.9% NaCl followed by topical treatment with Refresh Liquigel four times a day for four weeks.
| Study group | Role | What they receive |
|---|---|---|
| Avastin® (bevacizumab) | Active comparator | Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 mL (2.5 mg) bevacizumab. Starting Day 1 post-transplant surgery, subjects will begin treatment with topical bevacizumab (1% solution). Topical treatment will be self-administered 4 times a day for 4 weeks.
The study treatments are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule. Receives: Drug: Avastin® (bevacizumab) |
| 0.9% NaCl & Refresh Liquigel | Placebo comparator | Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 mL 0.9% NaCl. Starting Day 1 post-transplant surgery, subjects will begin treatment with topical Refresh Liquigel. Topical treatment will be self-administered 4 times a day for 4 weeks.
The study treatments (both topical and subconjunctival injection) are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule. Receives: Drug: 0.9% NaCl & Refresh Liquigel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelial Rejection Rate
Endothelial rejection rates in patients in the treatment group and the control group were calculated using the Kaplan-Meier survival curve. The Kaplan-Meier/product limit estimator is a non-parametric statistical test used to show the probability of an event occurring at a given time interval. The Kaplan-Meier estimator is used to show what the probability of corneal transplant rejection (and therefore transplant survival) after administration of the active treatment or control.
Measured: 12 Months
Number of Participants Experiencing Ocular Adverse Events
Incidence and severity of ocular adverse events during the study (based on ophthalmic examination and subject self-reporting).
Measured: 12 months
Incidence of Systemic Adverse Events
Incidence and severity of systemic adverse events during the study (based on physical examination, subject self-reporting, and changes in vital sign).
Measured: 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2013 (estimated)
- Study startApr 2014
- Primary completionApr 2019
- Study completionApr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Reza Dana, MD
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, Bascom Palmer Eye Institute, New York Presbyterian Hospital
- Responsible party
- Sponsor-investigator, Reza Dana, MD, Massachusetts Eye and Ear Infirmary
- Investigators
- Reza Dana, MD, MPH, MSc, Principal investigator, Massachusetts Eye and Ear Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01996826
- Sponsor's protocol ID
- 13-113H
- Status last verified
- Aug 2020
- First submitted
- 22 Nov 2013
- Last updated
- 10 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
- ClinicalTrials.gov ID
- NCT01996826
- Acronym / sponsor ID
- 13-113H
- Conditions
- Corneal Neovascularization, Corneal Graft Failure
- Keywords
- Corneal Neovascularization, Cornea Blood Vessels, Corneal Graft Failure, High-Risk Penetrating Keratoplasty, Corneal Transplant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Reza Dana, MDUniversity, hospital or other
- Collaborators
- United States Department of Defense, Bascom Palmer Eye Institute, New York Presbyterian Hospital
- Study start
- Apr 2014 (actual)
- Primary completion
- Apr 2019 (actual)
- Study completion
- Apr 2019 (actual)
- First posted
- 27 Nov 2013 (estimated)
- Results
- Posted 10 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to investigate whether using bevacizumab (Avastin®) is both safe and effective at decreasing the likelihood of a high-risk corneal graft rejection. Patients who are "high-risk" for rejection have blood vessels growing from the white of the eye into the cornea (clear, front region of the eye). The medication is used at the time of surgery and in the weeks following surgery. Participants have a 50/50 chance at receiving the active study medication or a placebo medication.
Detailed description
The purpose of this study is to test the effectiveness of a drug, bevacizumab (Avastin), in preventing blood vessels that often occur after a corneal transplantation which are considered at "high-risk" for rejection. In many cases these blood vessels lead to the graft rejection and eventual failure of the corneal transplant. It is hoped that this treatment will increase the chances of corneal graft survival.
The medication used in this study is called bevacizumab or Avastin (Genentech, Inc). It works by inhibiting the action of a molecule called vascular endothelial growth factor (VEGF). VEGF is a substance molecule that binds to certain cells to stimulate new blood vessel formation. When VEGF is bound to the drug, it cannot stimulate the formation and growth of new blood vessels. Growth of blood vessels into the cornea is a complication which can worsen the prognosis of your corneal transplant and put the transplant at a higher risk for rejection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Avastin® (bevacizumab) | Active comparator | Drug: Avastin® (bevacizumab)Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 mL (2.5 mg) bevacizumab. Starting Day 1 post-transplant surgery, subjects will begin treatment with topical bevacizumab (1% solution). Topical treatment will be self-administered 4 times a day for 4 weeks. The study treatments are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule. |
| 0.9% NaCl & Refresh Liquigel | Placebo comparator | Drug: 0.9% NaCl & Refresh LiquigelTreatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 mL 0.9% NaCl. Starting Day 1 post-transplant surgery, subjects will begin treatment with topical Refresh Liquigel. Topical treatment will be self-administered 4 times a day for 4 weeks. The study treatments (both topical and subconjunctival injection) are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age > 18 years
- Participant willing and able to provide written informed consent
- Willing and able to comply with study assessments for the full duration of the study
- High-risk characteristics for penetrating keratoplasty:
- In generally good stable overall health
Key exclusion criteria (14 listed)
- History of Stevens-Johnson syndrome or ocular pemphigoid
- Ocular or periocular malignancy
- Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
- Uncontrolled glaucoma
- Currently on dialysis
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 |
|---|---|---|
| Avastin® (bevacizumab)Also: Avastin®, bevacizumabOne time subconjunctival injection of 0.1 mL (2.5 mg) bevacizumab followed by topical treatment with 1% solution bevacizumab four times a day for four weeks. | Drug | Avastin® (bevacizumab) |
| 0.9% NaCl & Refresh LiquigelAlso: Sodium Chloride, Refresh Liquigel, NaCLOne-time subconjunctival injection of 0.1mL 0.9% NaCl followed by topical treatment with Refresh Liquigel four times a day for four weeks. | Drug | 0.9% NaCl & Refresh Liquigel |
Primary outcome
Endothelial Rejection Rate
Time frame: 12 Months
Endothelial rejection rates in patients in the treatment group and the control group were calculated using the Kaplan-Meier survival curve. The Kaplan-Meier/product limit estimator is a non-parametric statistical test used to show the probability of an event occurring at a given time interval. The Kaplan-Meier estimator is used to show what the probability of corneal transplant rejection (and therefore transplant survival) after administration of the active treatment or control.
Number of Participants Experiencing Ocular Adverse Events
Time frame: 12 months
Incidence and severity of ocular adverse events during the study (based on ophthalmic examination and subject self-reporting).
Incidence of Systemic Adverse Events
Time frame: 12 Months
Incidence and severity of systemic adverse events during the study (based on physical examination, subject self-reporting, and changes in vital sign).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Reza Dana, MD, MPH, MSc principal investigator
Massachusetts Eye and Ear Infirmary
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Avastin® (bevacizumab) and 0.9% NaCl & Refresh Liquigel in people with Corneal Neovascularization and Corneal Graft Failure, run by Reza Dana, MD at 3 sites in United States.
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 7 inclusion and 14 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 10 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Endothelial Rejection Rate (time frame: 12 Months). The study lists 3 primary outcomes in all. 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 10 Aug 2020.