Clinical trial NCT04584125: A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients
Official title: A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Keratoconus
Keywords: Corneal Crosslinking
Penetrating Keratoplasty
Deep Anterior Lamellar Keratoplasty
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
First posted: 2020-10-12
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: • Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery.
timeFrame: 130 weeks
Secondary outcomes:
measure: • Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery
timeFrame: 130 weeks
measure: Manifest cylinder astigmatism at 130 weeks post-surgery
timeFrame: 130 weeks
measure: Uncorrected visual acuity (UCVA) 130 weeks post-surgery
timeFrame: 130 weeks
measure: Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgery
timeFrame: 130 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
Study officials:
affiliation: Massachusetts Eye and Ear
name: Joseph B Ciolino
role: PRINCIPAL_INVESTIGATOR
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