Pretreatment to Promote Graft Survival After Subsequent High-risk Corneal Transplantation [CrossCornealVision]

NCT05870566 | Recruiting DMC

• 2 other identifiers: Uni-Koeln-504501KG2127
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 7

Brief Summary

The trial evaluates the effect of corneal crosslinking as pre-treatment before corneal transplantation. The goal is to improve graft survival by reducing pathological vessels through pre-treatment.

Conditions

Corneal Transplantation

Keywords

Cornea; Transplantation; Prevascularized Corneas; Corneal crosslinking with UV light irradiation

Outcome Measures

Primary Outcomes (1)

• First episode of endothelial graft rejection

  Endothelial graft rejection episode is defined by at least 2 of the following criteria: new endothelial precipitates, new anterior chamber cells/flare, new focal or diffuse edema of the graft. All signs will be analyzed by slit lamp examination, on standardized digital slit lamp pictures, by LaserFlareCellMeter (if available), SL-OCT and corneal tomography. (Protocol V04\_0 Page 48)

  within 24 months after transplantation

Secondary Outcomes (10)

• Regression of CoNV

  prior to and 2-4 weeks after each CXL, prior to transplantation and at 3, 6, 12, 18 and 24 months

• Regression of CoNV

  before transplantation

• Recurrence of CoNV

  after CXL and 3, 6, 12, 18 and 24 months after transplantation

• Overall functional graft survival rate

  3, 6, 12, 18 and 24 months after transplantation

• Absence of rejection-related graft failure

  3, 6, 12, 18 and 24 months after transplantation

Study Arms (2)

Corneal Crosslinking (CXL)

EXPERIMENTAL

In the intervention group, the study intervention (CXL) will be administered to stabilize therecipient cornea (which remains in place after penetrating keratoplasty) and to reduce CoNV 8 to 10 weeks prior to corneal transplantation. The study intervention will be repeated once (after 4 weeks prior to transplantation at the latest at the earliest) if insufficient (less than 50%) reduction of CoNV should be observed (to be decided by the respective surgeon). (Protocol V04\_0 Page 45) Corneal transplantation will be performed as standard full-thickness penetrating procedure, and the graft (6.5 to 8.25 in diameter) will be secured with 16-24 interrupted single or 2 double running 10-0 nylon sutures (decision by the surgeon). In case of residual CoNV in the intervention group, visible vessels will may be thermally occluded by fine needle diathermy to avoid intraoperative bleeding and reduce complications (to be decided by the respective surgeon at start of surgery). (Protocol V04\_0 Page 46)

Device: Corneal Crosslinking

control group

NO INTERVENTION

In the control group subjects will be directly scheduled for corneal transplantation without previous CXL. A sham CXL procedure will not be performed. Corneal transplantation will be performed as standard full-thickness penetrating procedure, and the graft (6.5 to 8.25 in diameter) will be secured with 16-24 interrupted single or 2 double running 10-0 nylon sutures (decision by the surgeon). In case of residual CoNV in the intervention group, visible vessels will may be thermally occluded by fine needle diathermy to avoid intraoperative bleeding and reduce complications (to be decided by the respective surgeon at start of surgery). In the control group, no fine needle diathermy will be performed, as this procedure combined with corneal transplantation in previously non-crosslinked eyes might lead to fistulas and thereby to potential intraocular infections. (Protocol V04\_0 Page 46)

Interventions

Corneal Crosslinking DEVICE

Riboflavin isotonic, 0,1 % Vitamin B2, with Dextran 20,0%, for epi-off procedure or Riboflavin isotonic 0,1% (Vitamin B2), 1,1% HPMC without Dextran for epi-off) 0.1% riboflavin-5-phosphate and 20% dextran T-500) will be applied to the cornea after epithelial debridement every 2 min for 10 minutes before irradiation and every 2 minutes during the course of a 10 minute exposure to 365 nm UV-A with an irradiance rate of 9 mW/cm2. This dose, mode and scheme of the intervention follows the internationally recognized "accelerated CXL protocol" (Elbaz et al. 2014). The data existing shows equivalent outcome regarding efficacy and safety compared to the standard protocol. To avoid any damage to the limbal stem cells, the limbus will not be irradiated during the procedure, as a CXL device (with maximal diameter of 11 mm) will be used. Furthermore, the limbal area will additionally be protected by a custom-cut LSC protection shield. (Protocol V04\_0 Page 45-46)

Corneal Crosslinking (CXL)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Medical condition or disease to be investigated:
• \- Pathologically prevascularized cornea with need for corneal transplantation
• Written informed consent by subject and/or witness prior to any study-related procedures
• Adult male and female subjects ≥ 18 years old
• ≥ 2 corneal quadrants covered by pathological corneal neovascularization
• Absence of other clinical contraindications to any part or product of the treatment plan
• A cooperative attitude to follow up the study procedures
• In case of bilateral disease only one eye will be included
• Steroid responders with adequate control regiment or local/systemic therapy can be included

You may not qualify if:

• \< 2 corneal quadrants covered by pathological neovascularization
• Corneal stromal thickness below 400 μm (except in the central 8 mm zone which will be replaced later by a new corneal transplant with new endothelium); peripheral stromal thinning below 400 μm in weakened recipient areas is acceptable for CXL if not affecting more than 50% of the corneal circumference (allowing for later endothelial repopulation)
• Active or suspected intraocular inflammation
• Active corneal ulceration
• Compromised eyelid mobility and/or symblepharon
• Allergy, sensitivity or intolerance to riboflavin or UV
• Contraindications, other than steroid response to the local or systemic antibiotics and/or corticosteroids (other than steroid response) foreseen by the protocol
• Contraindications to the surgical protocol
• Clinically significant or unstable concurrent disease or other medical condition affecting grafting procedure
• Rheumatic diseases treated with systemic immunosuppressive medication
• Subjects unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study procedures and treatments
• Participation in another clinical trial where an investigational drug was received less than 4 weeks prior to screening visit
• Positive for human immunodeficiency virus (HIV)
• Known abuse of alcohol, drugs, or medicinal products
• Evidence of any other medical conditions (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the subject's compliance, or place the subject at high risk of complications related to the treatment

Sponsors & Collaborators

• Claus Cursiefen: lead
• Uniklinik Köln, Zentrum für Klinische Studien: collaborator
• Uniklinik Köln, Institut für Medizinische Statistik und Bioinformatik: collaborator
• German Federal Ministry of Education and Research: collaborator

Study Sites (7)

Augenklinik des Klinikums der Universität München

München, Bavaria, 80336, Germany

RECRUITING

University Hospital of Cologne, Centre for Ophthalmology

Cologne, North Rhine-Westphalia, 50937, Germany

RECRUITING

Universitätsklinikum Düsseldorf, Klinik für Augenheilkunde

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Universitätsklinikum des Saarlandes, Klinik für Augenheilkunde

Homburg, Saarland, 66424, Germany

RECRUITING

Charité - Universitätsmedizin Berlin, Klinik für Augenheilkunde

Berlin, 13353, Germany

RECRUITING

Universitätsklinikum Freiburg, Klinik für Augenheilkunde

Freiburg im Breisgau, 79106, Germany

RECRUITING

Klinik und Poliklinik für Augenheilkunde - Universitätsmedizin Rostock

Rostock, 18057, Germany

RECRUITING

Related Publications (1)

• Wiedemann J, Hos D, Limburg E, Zettelmeyer U, Schiller P, Franklin J, Bachmann B, Bohringer D, Dietrich-Ntoukas T, Fuchsluger TA, Geerling G, Lang SJ, Mayer WJ, Priglinger S, Reinhard T, Seitz B, Cursiefen C. UV light-mediated corneal crosslinking as (lymph)angioregressive pretreatment to promote graft survival after subsequent high-risk corneal transplantation (CrossCornealVision): protocol for a multicenter, randomized controlled trial. Trials. 2024 Mar 6;25(1):169. doi: 10.1186/s13063-024-08011-1.

  PMID: 38448965 DERIVED

MeSH Terms

Conditions

Corneal Diseases

Condition Hierarchy (Ancestors)

Eye Diseases

Study Officials

• Claus Cursiefen, Prof. Dr.

  University Hospital of Cologne, Centre for Ophthalmology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claus Cursiefen, Prof. Dr.

CONTACT

00492214784300; marie.seifert@uk-koeln.de

Deniz Hos, Dr.

CONTACT

004922147898896; deniz.hos@uk-koeln.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: Prospective, multicenter, open randomized parallel-group trial

Study Record Dates

• First Submitted: May 3, 2023
• First Posted: May 23, 2023
• Study Start: November 20, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: October 21, 2024

Record last verified: 2024-10

Locations

DE (7)