A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients (EVOKE)
Primary Purpose
Keratoconus
Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% with UV light
Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% without UV light
Sponsored by
About this trial
This is an interventional treatment trial for Keratoconus focused on measuring Corneal Crosslinking, Penetrating Keratoplasty, Deep Anterior Lamellar Keratoplasty
Eligibility Criteria
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 a penetrating 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
Sites / Locations
- Massachusetts Eye and Ear Infirmary
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Ex vivo cross linking of donor corneal tissue
Non-cross-linked donor corneal tissue for keratoplasty
Arm Description
Treatment Arm: The donor corneal tissue used in the PK or DALK procedures will previously undergo ex vivo crosslinking.
Control Arm: The donor corneal tissue used in the PK or DALK procedures will not previously undergo ex vivo crosslinking.
Outcomes
Primary Outcome Measures
• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery.
• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery
Secondary Outcome Measures
• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
Manifest cylinder astigmatism at 130 weeks post-surgery
Manifest cylinder astigmatism at 130 weeks post-surgerykeratometry, anterior mean keratometry, posterior mean keratometry
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgery
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgerypermeable contact lens.
Full Information
NCT ID
NCT04584125
First Posted
October 5, 2020
Last Updated
January 12, 2023
Sponsor
Joseph B. Ciolino, MD
1. Study Identification
Unique Protocol Identification Number
NCT04584125
Brief Title
A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients
Acronym
EVOKE
Official Title
A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2023 (Anticipated)
Primary Completion Date
May 1, 2028 (Anticipated)
Study Completion Date
November 30, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Joseph B. Ciolino, MD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Keratoconus
Keywords
Corneal Crosslinking, Penetrating Keratoplasty, Deep Anterior Lamellar Keratoplasty
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The study is a multicenter, double-masked, parallel, and randomized study with a subsequent follow-up period of 30 months. 216 subjects (of any race or gender) who have keratoconus (between the ages of 18 and 50) will sign the consent for their first PK or DALK surgery in the study eye. Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be given the opportunity to participate in the study. Subjects will either randomized to the treatment group (crosslinked corneal tissue) or control group (non-crosslinked corneal tissue that has been exposed to riboflavin, but no ultraviolet light).
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
216 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ex vivo cross linking of donor corneal tissue
Arm Type
Experimental
Arm Description
Treatment Arm: The donor corneal tissue used in the PK or DALK procedures will previously undergo ex vivo crosslinking.
Arm Title
Non-cross-linked donor corneal tissue for keratoplasty
Arm Type
Sham Comparator
Arm Description
Control Arm: The donor corneal tissue used in the PK or DALK procedures will not previously undergo ex vivo crosslinking.
Intervention Type
Drug
Intervention Name(s)
Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% with UV light
Other Intervention Name(s)
PHOTREXA VISCOUS
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% without UV light
Other Intervention Name(s)
PHOTREXA VISCOUS
Intervention Description
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.
Primary Outcome Measure Information:
Title
• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery.
Description
• Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery
Time Frame
130 weeks
Secondary Outcome Measure Information:
Title
• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
Description
• Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
Time Frame
130 weeks
Title
Manifest cylinder astigmatism at 130 weeks post-surgery
Description
Manifest cylinder astigmatism at 130 weeks post-surgerykeratometry, anterior mean keratometry, posterior mean keratometry
Time Frame
130 weeks
Title
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
Description
Uncorrected visual acuity (UCVA) 130 weeks post-surgery
Time Frame
130 weeks
Title
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgery
Description
Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgerypermeable contact lens.
Time Frame
130 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joseph B Ciolino, MD
Phone
(617) 573-3938
Email
Joseph_Ciolino@MEEI.HARVARD.EDU
First Name & Middle Initial & Last Name or Official Title & Degree
Ellen Fitzgerald
Phone
617-573-6971
Email
Ellen_Fitzgerald@MEEI.HARVARD.EDU
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph B Ciolino
Organizational Affiliation
Massachusetts Eye and Ear
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
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Ciolino, MD
Phone
617-573-5575
Email
Joseph_Ciolino@meei.harvard.edu
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
There is not a plan to make individual participant data (IPD) available.
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A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients
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