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

February 18, 2010
June 21, 2013
December 2009
June 2016   (final data collection date for primary outcome measure)
Endothelial Rejection Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01072357 on ClinicalTrials.gov Archive Site
  • 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
  • Time from surgery to the occurrence of any rejection episode or overall graft failure [ Time Frame: 16, 26, and 52 weeks ] [ Designated as safety issue: No ]
  • Endothelial density and central corneal thickness [ Time Frame: 16, 26, and 52 weeks ] [ Designated as safety issue: No ]
  • Corneal NV metrics [ Time Frame: 16, 26, and 52 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Corneal Neovascularization
  • Corneal Graft Failure
  • 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
  • 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
  • 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.

    Intervention: Drug: 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.

    Intervention: Drug: 0.9% NaCl & Refresh Liquigel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
110
October 2016
June 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Cornea Research (617) 573-3313 Cornea_Research@meei.harvard.edu
United States
 
NCT01072357
09-07-062
Yes
Massachusetts Eye and Ear Infirmary
Massachusetts Eye and Ear Infirmary
  • Bascom Palmer Eye Institute
  • New York Presbyterian Hospital
  • Department of Defense
Principal Investigator: Reza Dana, MD, MPH, MSc Massachusetts Eye and Ear Infirmary
Massachusetts Eye and Ear Infirmary
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP