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

This study is currently recruiting participants.
Verified April 2012 by Massachusetts Eye and Ear Infirmary
Sponsor:
Information provided by (Responsible Party):
Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier:
NCT01072357
First received: February 18, 2010
Last updated: April 19, 2012
Last verified: April 2012
History of Changes
  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
 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:

U.S. FDA Resources

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 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 ]

Estimated Enrollment: 80
Study Start Date: December 2009
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active

Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of either 0.1mL (2.5 mg) bevacizumab. Starting Day 1 post-transplant surgery, subjects will begin treatment with either 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 0.1mL (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: Vehicle

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

    • Presence of corneal NV in one or more quadrants (≥ 3 clock hours NV ≥ 2mm from the limbus) OR
    • 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
  • Uncontrolled glaucoma
  • 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
  • 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
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
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: April 19, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts Eye and Ear Infirmary:
High-Risk Corneal Transplantation

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

ClinicalTrials.gov processed this record on May 16, 2013