Corneal Graft Failure, Corneal Neovascularization
Conditions
Keywords
High-Risk Corneal Transplantation, Penetrating Keratoplasty, Neovascularization, Corneal Blood Vessels, Avastin, Bevacizumab, Corneal Graft
Brief summary
The leading risk factor for corneal transplant rejection is abnormal blood vessel growth of the host bed. Vascular endothelial growth factor (VEGF) is thought to be a mediator of this corneal neovascularization (NV), therefore we would like to test the safety and efficacy of local VEGF blockade in the promotion of graft survival in high risk corneal transplants.
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.
Interventions
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.
One-time subconjunctival injection of 0.1mL 0.9% NaCl followed by topical treatment with Refresh Liquigel four times a day for four weeks
Sponsors
Reza Dana, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Patient or legally authorized representative 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: Either presence of 1.) Corneal NV in one or more quadrants (≥ 3 clock hours NV ≥ 2mm from the limbus) OR 2.) Extension of corneal NV to graft-host junction in a previous failed graft * In generally good stable overall health
Exclusion criteria
* 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Graft Failure at Week 39 and 52 | 12 months | Time from surgery to overall graft failure (regardless of cause). Graft failure was monitored throughout the entire study, but only the time points at which graft failure occurred are reported below. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial Cell Density | 52 Weeks | Endothelial Cell Density (Assessed at Weeks 26 & 52). Measure of the number of cells present within the endothelium that are responsible for providing the cornea with nourishment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Avastin® (Bevacizumab) Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 milliliter (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.
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. | 15 |
| 0.9% NaCl & Refresh Liquigel Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 mL 0.9% sodium chloride (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.
0.9% NaCl & Refresh Liquigel: One-time subconjunctival injection of 0.1mL 0.9% NaCl followed by topical treatment with Refresh Liquigel four times a day for four weeks | 14 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | 0.9% NaCl & Refresh Liquigel | Total | Avastin® (Bevacizumab) |
|---|---|---|---|
| Age, Continuous | 63.0 years STANDARD_DEVIATION 13 | 67.2 years STANDARD_DEVIATION 15.5 | 71.3 years STANDARD_DEVIATION 17 |
| Race/Ethnicity, Customized African American | 3 Participants | 7 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 18 Participants | 8 Participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 13 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 13 / 15 | 13 / 15 |
| serious Total, serious adverse events | 1 / 15 | 1 / 15 |
Outcome results
Primary
Number of Participants With Graft Failure at Week 39 and 52
Time from surgery to overall graft failure (regardless of cause). Graft failure was monitored throughout the entire study, but only the time points at which graft failure occurred are reported below.
Time frame: 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avastin® (Bevacizumab) | Number of Participants With Graft Failure at Week 39 and 52 | 52 Week Time Point | 1 Participants |
| Avastin® (Bevacizumab) | Number of Participants With Graft Failure at Week 39 and 52 | 39 Week Time Point | 0 Participants |
| 0.9% NaCl & Refresh Liquigel | Number of Participants With Graft Failure at Week 39 and 52 | 52 Week Time Point | 1 Participants |
| 0.9% NaCl & Refresh Liquigel | Number of Participants With Graft Failure at Week 39 and 52 | 39 Week Time Point | 1 Participants |
Secondary
Endothelial Cell Density
Endothelial Cell Density (Assessed at Weeks 26 & 52). Measure of the number of cells present within the endothelium that are responsible for providing the cornea with nourishment.
Time frame: 52 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avastin® (Bevacizumab) | Endothelial Cell Density | Week 26 Time Point | 1814.25 Number of cells per millimeters squared | Standard Deviation 729.72 |
| Avastin® (Bevacizumab) | Endothelial Cell Density | Week 52 Time Point | 1432.50 Number of cells per millimeters squared | Standard Deviation 696.61 |
| 0.9% NaCl & Refresh Liquigel | Endothelial Cell Density | Week 26 Time Point | 2249.83 Number of cells per millimeters squared | Standard Deviation 891.25 |
| 0.9% NaCl & Refresh Liquigel | Endothelial Cell Density | Week 52 Time Point | 1926.67 Number of cells per millimeters squared | Standard Deviation 948.03 |