Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival

Corneal Neovascularization Clinical Trial

Official title:

Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01072357
• Other study ID #: 09-07-062
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2009
• Est. completion date: January 2015

Study information

• Verified date: May 2018
• Source: Massachusetts Eye and Ear Infirmary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Corneal Graft Failure
• Corneal Neovascularization
• Neovascularization, Pathologic

Intervention

Drug:
• 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 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

Locations

Country	Name	City	State
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Reza Dana, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	12 months
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.	52 Weeks