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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Massachusetts Eye and Ear Infirmary
Sponsor:
Collaborators:
Bascom Palmer Eye Institute
New York Presbyterian Hospital
Information provided by (Responsible Party):
Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier:
NCT01072357
First received: February 18, 2010
Last updated: June 21, 2013
Last verified: June 2013
  Purpose

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, 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.


Condition Intervention Phase
Corneal Neovascularization
Corneal Graft Failure
Drug: Avastin® (bevacizumab)
Drug: 0.9% NaCl & Refresh Liquigel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival

Resource links provided by NLM:


Further study details as provided by Massachusetts Eye and Ear Infirmary:

Primary Outcome Measures:
  • Endothelial Rejection Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time from Surgery to Any Rejection Episode [ Time Frame: 16, 26, and 52 weeks ] [ Designated as safety issue: No ]
    Time from surgery to occurrence of any rejection episode (endothelial, epithelial, subepithelial)

  • Time from Surgery to Graft Failure [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Time from surgery to overall graft failure (regardless of cause)

  • Incidence of Delayed Epithelial Healing [ Time Frame: 7 days Post-Op ] [ Designated as safety issue: No ]
  • Endothelial Cell Density [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Endothelial Cell Density (Compared at Weeks 26 & 52)

  • Central Corneal Thickness [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Central corneal thickness at Weeks 16, 26, and 52

  • Frequency of Primary Graft Failure [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
  • Corneal NV Metrics [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]

    Corneal NV Metrics

    • Neovascular Area (NA), measuring the area of the corneal vessels themselves
    • Vessel Caliber (VC), measuring the mean diameter of the corneal vessels
    • Invasion Area (IA), measuring the fraction of corneal area in which vessels are present


Estimated Enrollment: 110
Study Start Date: December 2009
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.

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.
Other Names:
  • Avastin
  • bevacizumab
Placebo Comparator: 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.

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
Other Names:
  • Sodium Chloride
  • Refresh Liquigel
  • NaCL

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01072357

Contacts
Contact: Cornea Research (617) 573-3313 Cornea_Research@meei.harvard.edu

Locations
United States, Massachusetts
Massachusetts Eye and Ear Infirmary Recruiting
Boston, Massachusetts, United States, 02114
Contact: Cornea Research    617-573-3313    Cornea_Research@meei.harvard.edu   
Sponsors and Collaborators
Massachusetts Eye and Ear Infirmary
Bascom Palmer Eye Institute
New York Presbyterian Hospital
Investigators
Principal Investigator: Reza Dana, MD, MPH, MSc Massachusetts Eye and Ear Infirmary
  More Information

No publications provided

Responsible Party: Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT01072357     History of Changes
Other Study ID Numbers: 09-07-062
Study First Received: February 18, 2010
Last Updated: June 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts Eye and Ear Infirmary:
High-Risk Corneal Transplantation
Penetrating Keratoplasty
Neovascularization
Corneal Blood Vessels
Avastin
Bevacizumab
Corneal Graft

Additional relevant MeSH terms:
Neovascularization, Pathologic
Corneal Neovascularization
Metaplasia
Pathologic Processes
Corneal Diseases
Eye Diseases
Bevacizumab
Carboxymethylcellulose Sodium
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Laxatives
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 18, 2014