A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival

Corneal Neovascularization Clinical Trial

Official title:

A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01996826
• Other study ID #: 13-113H
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2014
• Est. completion date: April 2019

Study information

• Verified date: August 2020
• Source: Massachusetts Eye and Ear Infirmary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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: 75
• Est. completion date: April 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	New York Presbyterian Hospital	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Reza Dana, MD	Bascom Palmer Eye Institute, New York Presbyterian Hospital, United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 Months
Primary	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).	12 months
Primary	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).	12 Months