A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients (EVOKE)

January 12, 2023 updated by: Joseph B. Ciolino, MD

A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus

This randomized clinical trial will assess corneal astigmatism and visual outcomes in participants who have undergone corneal transplantation for keratoconus with ex vivo cross-linked donor corneal tissue versus participants who have undergone corneal transplantation for keratoconus with non-cross-linked donor corneas. Crosslinking is a procedure that stabilizes the biomechanical properties of the cornea; as a result, the cornea stiffens. It has been shown that this procedure stabilizes the cornea of patients with keratoconus or corneal ectasias. The FDA currently approves crosslinking for patients with progressive keratoconus and corneal ectasia following refractive surgery. Ex vivo crosslinking of donor corneal tissue for patients with keratoconus undergoing PK or DALK could stabilize the cornea and reduce the risk of high astigmatism and improve vision in patient with keratoconus.

Study Overview

Detailed Description

The 15 clinical sites are expected to recruit cumulatively 216 cases over 18 months. Eligibility is assessed during a routine examination by an investigator. Informed consent will be obtained prior to collecting any information that is not part of usual care. Patients who meet all inclusion criteria and none of the exclusion criteria will be given the opportunity to participate in the study. Participants will be randomly assigned to the treatment group (cross-linked corneal tissue) or control group (non-cross-linked corneal tissue that has been exposed to riboflavin, but no ultraviolet light).

The investigator will request a cadaveric cornea from the study's central eye bank CorneaGen, which will prepare the cadaveric cornea. Participants will receive the cross-linked donor tissue or control donor tissue during surgery. Clinical sites, including surgeons, and participants will be masked to treatment assignment.

Participants will be followed up post-operatively by the site investigators as per the standard of care. This will include visits at 1 Day, 1 Week, 1 Month, 6 Months, 1 Year, 1.5 Years, 2 Years, and 2.5 Years post-surgery. Some participants may need to be seen more regularly for routine care. The investigators will monitor for systemic and ocular adverse events at all follow-up visits.

Study Type

Interventional

Enrollment (Anticipated)

216

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Willing and able to provide written informed consent.
  • Willing and able to comply with study assessments for the full duration of the study.
  • Age ≥18 years but ≤50 years
  • History of keratoconus (without a previous transplant) requiring keratoplasty
  • Willing to commit to not having further cross-linking, corneal relaxing incisions, intacs, or corneal laser vision correction during the course of the study

Exclusion Criteria:

  • Age < 18 years >50
  • Inability to provide written informed consent and comply with study assessments for the full duration of the study
  • Participation in another simultaneous interventional medical investigation or trial

Systemic

  • History of Stevens-Johnson syndrome or ocular pemphigoid
  • Signs of current infection, including fever and current treatment with antibiotics
  • Pregnancy (positive pregnancy test) or lactating
  • Pre-menopausal sexually active women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method)

Recipient Eye

  • Corneal or ocular surface infection within 30 days prior to study entry
  • History of previous cross-linking
  • History of previous corneal transplant
  • Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
  • Ocular or periocular malignancy
  • Lid abnormalities that in the opinion of the investigator could confound the study results and these include clinically significant ectropion, lagophthalmos, cicatrization, entropion, and rosacea
  • Neurotrophic cornea
  • Monocular
  • Uncontrolled glaucoma
  • Glaucoma filtering devices or trabeculectomies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ex vivo cross linking of donor corneal tissue
Treatment Arm: The donor corneal tissue used in the PK or DALK procedures will previously undergo ex vivo crosslinking.
A wavelength of 365 nm ultraviolet A light will be used to direct 5.4 J/cm2 using a beam diameter of 9.5mm to treat the de-epithelialized corneal surface of a donor cornea for 30 minutes. Every 2 minutes, the UV light will be used while another drop of riboflavin is applied on top of the donor cornea.
Other Names:
  • PHOTREXA VISCOUS
Sham Comparator: Non-cross-linked donor corneal tissue for keratoplasty
Control Arm: The donor corneal tissue used in the PK or DALK procedures will not previously undergo ex vivo crosslinking.
The corneal tissue for the control arm will be treated the same as the crosslinked tissue except that it will not be exposed to ultraviolet light. The donor cornea will be placed on an artificial anterior chamber maintainer and the epithelium will be removed mechanically. Riboflavin solution (0.1% riboflavin and 20% dextran supplied in a sterile, single-dose container) will be applied to the cornea every 2 minutes for 30 minutes.
Other Names:
  • PHOTREXA VISCOUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery.
Time Frame: 130 weeks
• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery
130 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
Time Frame: 130 weeks
• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
130 weeks
Manifest cylinder astigmatism at 130 weeks post-surgery
Time Frame: 130 weeks
Manifest cylinder astigmatism at 130 weeks post-surgerykeratometry, anterior mean keratometry, posterior mean keratometry
130 weeks
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
Time Frame: 130 weeks
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
130 weeks
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgery
Time Frame: 130 weeks
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgerypermeable contact lens.
130 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Joseph B Ciolino, Massachusetts Eye and Ear

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2023

Primary Completion (Anticipated)

May 1, 2028

Study Completion (Anticipated)

November 30, 2028

Study Registration Dates

First Submitted

October 5, 2020

First Submitted That Met QC Criteria

October 9, 2020

First Posted (Actual)

October 12, 2020

Study Record Updates

Last Update Posted (Estimate)

January 16, 2023

Last Update Submitted That Met QC Criteria

January 12, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There is not a plan to make individual participant data (IPD) available.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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