Clinical trial NCT01996826: A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
Official title: A Multi-Center Study of the 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: Corneal Neovascularization
Cornea Blood Vessels
Corneal Graft Failure
High-Risk Penetrating Keratoplasty
Corneal Transplant
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Bascom Palmer Eye Institute
name: New York Presbyterian Hospital
First posted: 2013-11-27
Enrollment: 75
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 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.

Eligibility criteria: Inclusion Criteria:

* 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:

  1. Presence of 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: Endothelial Rejection Rate
timeFrame: 12 Months
measure: Number of Participants Experiencing Ocular Adverse Events
timeFrame: 12 months
measure: Incidence of Systemic Adverse Events
timeFrame: 12 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
Study officials:
affiliation: Massachusetts Eye and Ear Infirmary
name: Reza Dana, MD, MPH, MSc
role: PRINCIPAL_INVESTIGATOR
References: