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A Multi-Center Study of the 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 Corneal Neovascularization, Cornea Blood Vessels, Corneal Graft Failure, High-Risk Penetrating Keratoplasty, Corneal Transplant

Eligibility Criteria

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

Inclusion Criteria:

  • Age > 18 years
  • Participant 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:

    1. Presence of 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

  • Bascom Palmer Eye Institute
  • Massachusetts Eye and Ear Infirmary
  • New York Presbyterian Hospital

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 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% 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

Endothelial Rejection Rate
Endothelial rejection rates in patients in the treatment group and the control group were calculated using the Kaplan-Meier survival curve. The Kaplan-Meier/product limit estimator is a non-parametric statistical test used to show the probability of an event occurring at a given time interval. The Kaplan-Meier estimator is used to show what the probability of corneal transplant rejection (and therefore transplant survival) after administration of the active treatment or control.
Number of Participants Experiencing Ocular Adverse Events
Incidence and severity of ocular adverse events during the study (based on ophthalmic examination and subject self-reporting).
Incidence of Systemic Adverse Events
Incidence and severity of systemic adverse events during the study (based on physical examination, subject self-reporting, and changes in vital sign).

Secondary Outcome Measures

Full Information

First Posted
November 22, 2013
Last Updated
August 6, 2020
Sponsor
Reza Dana, MD
Collaborators
United States Department of Defense, Bascom Palmer Eye Institute, New York Presbyterian Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01996826
Brief Title
A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
Official Title
A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
April 2014 (Actual)
Primary Completion Date
April 2019 (Actual)
Study Completion Date
April 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Reza Dana, MD
Collaborators
United States Department of Defense, Bascom Palmer Eye Institute, New York Presbyterian Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this study is to investigate whether using bevacizumab (Avastin®) is both safe and effective at decreasing the likelihood of a high-risk corneal graft rejection. Patients who are "high-risk" for rejection have blood vessels growing from the white of the eye into the cornea (clear, front region of the eye). The medication is used at the time of surgery and in the weeks following surgery. Participants have a 50/50 chance at receiving the active study medication or a placebo medication.
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
Corneal Neovascularization, Cornea Blood Vessels, Corneal Graft Failure, High-Risk Penetrating Keratoplasty, Corneal Transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
75 (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 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% 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
Endothelial Rejection Rate
Description
Endothelial rejection rates in patients in the treatment group and the control group were calculated using the Kaplan-Meier survival curve. The Kaplan-Meier/product limit estimator is a non-parametric statistical test used to show the probability of an event occurring at a given time interval. The Kaplan-Meier estimator is used to show what the probability of corneal transplant rejection (and therefore transplant survival) after administration of the active treatment or control.
Time Frame
12 Months
Title
Number of Participants Experiencing Ocular Adverse Events
Description
Incidence and severity of ocular adverse events during the study (based on ophthalmic examination and subject self-reporting).
Time Frame
12 months
Title
Incidence of Systemic Adverse Events
Description
Incidence and severity of systemic adverse events during the study (based on physical examination, subject self-reporting, and changes in vital sign).
Time Frame
12 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age > 18 years Participant 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 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
Bascom Palmer Eye Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Massachusetts Eye and Ear Infirmary
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival

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