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

Primary Purpose

Corneal Neovascularization, Corneal Graft Failure

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Avastin® (bevacizumab)
0.9% NaCl & Refresh Liquigel
Sponsored by
Reza Dana, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corneal Neovascularization focused on measuring High-Risk Corneal Transplantation, Penetrating Keratoplasty, Neovascularization, Corneal Blood Vessels, Avastin, Bevacizumab, Corneal Graft

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts Eye and Ear Infirmary

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Avastin® (bevacizumab)

0.9% NaCl & Refresh Liquigel

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants With Graft Failure at Week 39 and 52
Time from surgery to overall graft failure (regardless of cause). Graft failure was monitored throughout the entire study, but only the time points at which graft failure occurred are reported below.

Secondary Outcome Measures

Endothelial Cell Density
Endothelial Cell Density (Assessed at Weeks 26 & 52). Measure of the number of cells present within the endothelium that are responsible for providing the cornea with nourishment.

Full Information

First Posted
February 18, 2010
Last Updated
May 17, 2018
Sponsor
Reza Dana, MD
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1. Study Identification

Unique Protocol Identification Number
NCT01072357
Brief Title
Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
Official Title
Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Reza Dana, MD

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corneal Neovascularization, Corneal Graft Failure
Keywords
High-Risk Corneal Transplantation, Penetrating Keratoplasty, Neovascularization, Corneal Blood Vessels, Avastin, Bevacizumab, Corneal Graft

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Avastin® (bevacizumab)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
0.9% NaCl & Refresh Liquigel
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Avastin® (bevacizumab)
Other Intervention Name(s)
Avastin, bevacizumab
Intervention Description
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
Intervention Name(s)
0.9% NaCl & Refresh Liquigel
Other Intervention Name(s)
Sodium Chloride, Refresh Liquigel, NaCL
Intervention Description
One-time subconjunctival injection of 0.1mL 0.9% NaCl followed by topical treatment with Refresh Liquigel four times a day for four weeks
Primary Outcome Measure Information:
Title
Number of Participants With Graft Failure at Week 39 and 52
Description
Time from surgery to overall graft failure (regardless of cause). Graft failure was monitored throughout the entire study, but only the time points at which graft failure occurred are reported below.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Endothelial Cell Density
Description
Endothelial Cell Density (Assessed at Weeks 26 & 52). Measure of the number of cells present within the endothelium that are responsible for providing the cornea with nourishment.
Time Frame
52 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reza Dana, MD, MPH, MSc
Organizational Affiliation
Massachusetts Eye and Ear Infirmary
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts Eye and Ear Infirmary
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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