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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01996826
Recruitment Status : Completed
First Posted : November 27, 2013
Last Update Posted : November 15, 2019
Sponsor:
Collaborators:
United States Department of Defense
Bascom Palmer Eye Institute
New York Presbyterian Hospital
Information provided by (Responsible Party):
Reza Dana, MD, Massachusetts Eye and Ear Infirmary

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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-Center Study of the Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
Actual Study Start Date : April 2014
Actual Primary Completion Date : April 2019
Actual Study Completion Date : April 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Endothelial Rejection Rate [ Time Frame: 12 Months ]
  2. Incidence of Ocular Adverse Events [ Time Frame: 12 months ]
    Incidence and severity of ocular adverse events during the study (based on ophthalmic examination and subject self-reporting).

  3. Incidence of Systemic Adverse Events [ Time Frame: 12 Months ]
    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 :
  1. Time from Surgery to Any Rejection Episode [ Time Frame: 16, 26, and 52 weeks post-op ]
    Time from surgery to occurrence of any rejection episode (endothelial, epithelial, subepithelial)

  2. Time from Surgery to Graft Failure [ Time Frame: 12 Months ]
    Time from surgery to overall graft failure (regardless of cause)

  3. Incidence of Delayed Epithelial Healing [ Time Frame: 7 days post-op ]
  4. Endothelial Cell Density [ Time Frame: 52 Weeks ]
    Endothelial Cell Density (Compared at Weeks 26 & 52)

  5. Central Corneal Thickness [ Time Frame: 52 Weeks ]
    Central corneal thickness at Weeks 16, 26, and 52

  6. Frequency of Primary Graft Failure [ Time Frame: 52 Weeks ]
  7. Change in Corneal Neovascularization Metrics [ Time Frame: 52 weeks ]

    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




Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01996826


Locations
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United States, Florida
Bascom Palmer Eye Institute
Miami, Florida, United States, 33136
United States, Massachusetts
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, United States, 02114
United States, New York
New York Presbyterian Hospital
New York, New York, United States, 10065
Sponsors and Collaborators
Reza Dana, MD
United States Department of Defense
Bascom Palmer Eye Institute
New York Presbyterian Hospital
Investigators
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Principal Investigator: Reza Dana, MD, MPH, MSc Massachusetts Eye and Ear Infirmary

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Responsible Party: Reza Dana, MD, Director, Cornea and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT01996826    
Other Study ID Numbers: 13-113H
First Posted: November 27, 2013    Key Record Dates
Last Update Posted: November 15, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Keywords provided by Reza Dana, MD, Massachusetts Eye and Ear Infirmary:
Corneal Neovascularization
Cornea Blood Vessels
Corneal Graft Failure
High-Risk Penetrating Keratoplasty
Corneal Transplant
Additional relevant MeSH terms:
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Corneal Neovascularization
Neovascularization, Pathologic
Metaplasia
Pathologic Processes
Corneal Diseases
Eye Diseases
Bevacizumab
Carboxymethylcellulose Sodium
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Laxatives
Gastrointestinal Agents