Clinical trial NCT01072357: Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
Official title: Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Corneal Neovascularization
Corneal Graft Failure
Keywords: High-Risk Corneal Transplantation
Penetrating Keratoplasty
Neovascularization
Corneal Blood Vessels
Avastin
Bevacizumab
Corneal Graft
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
First posted: 2010-02-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Graft Failure at Week 39 and 52
timeFrame: 12 months
Secondary outcomes:
measure: Endothelial Cell Density
timeFrame: 52 Weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
Study officials:
affiliation: Massachusetts Eye and Ear Infirmary
name: Reza Dana, MD, MPH, MSc
role: PRINCIPAL_INVESTIGATOR
References: