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

NCT ID: NCT01996826

Last Updated: 2020-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2019-04-30

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.

Conditions

Corneal Neovascularization; Corneal Graft Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Avastin® (bevacizumab)

Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 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.

Group Type: ACTIVE_COMPARATOR

Avastin® (bevacizumab)

Intervention Type: DRUG

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

Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 mL 0.9% 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.

Group Type: PLACEBO_COMPARATOR

0.9% NaCl & Refresh Liquigel

Intervention Type: DRUG

One-time subconjunctival injection of 0.1mL 0.9% NaCl followed by topical treatment with Refresh Liquigel four times a day for four weeks.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Avastin®; bevacizumab; Sodium Chloride; Refresh Liquigel; NaCL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Bascom Palmer Eye Institute

OTHER

Sponsor Role: collaborator

New York Presbyterian Hospital

OTHER

Sponsor Role: collaborator

Reza Dana, MD

OTHER

Sponsor Role: lead

Responsible Party

Reza Dana, MD

Director, Cornea and Refractive Surgery Service

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Reza Dana, MD, MPH, MSc

Role: PRINCIPAL_INVESTIGATOR

Massachusetts Eye and Ear Infirmary

Locations

Bascom Palmer Eye Institute

Miami, Florida, United States

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

New York Presbyterian Hospital

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

13-113H

Identifier Type: -

Identifier Source: org_study_id