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

NCT ID: NCT01072357

Last Updated: 2018-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2015-01-31

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.

Conditions

Corneal Neovascularization; Corneal Graft Failure

Study Design

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

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 milliliter (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% sodium chloride (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
• 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

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

Sponsors

Reza Dana, MD

OTHER

Sponsor Role: lead

Responsible Party

Reza Dana, MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Reza Dana, MD, MPH, MSc

Role: PRINCIPAL_INVESTIGATOR

Massachusetts Eye and Ear Infirmary

Locations

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

09-07-062

Identifier Type: -

Identifier Source: org_study_id