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

NCT ID: NCT05870566

Last Updated: 2024-10-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-20

Study Completion Date

2028-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Multicenter, two armed, controlled, open randomised parallel-group study to evaluate the effect of corneal crosslinking as pre-treatment vs. no pre-treatment ahead of full-thickness penetrating corneal transplantation.

After screening of inclusion and exclusion criteria, eligible subjects will be included after obtaining informed consent. Randomisation will be performed at a 5:4 ratio. (Protocol V04\_0 Page 37) At the baseline assessment, a slit lamp examination and photo documentation as well as LaserFlareCellMeter (if available), corneal tomography, and Slit lamp Adapted Optical Coherence Tomography (SL-OCT) measurements will be performed. In addition, visual acuity and a vision-related quality of life will be assessed. Concomitant medication will be documented. Macula OCT will be performed if deemed necessary. In the intervention arm, the study intervention (CXL) will then be administered to reduce CoNV 10-8 weeks prior to corneal transplantation. Two weeks after CXL a control will be performed including AE documentation, slit lamp examination, SL-OCT, corneal tomography, visual acuity and photo documentation. The study intervention will be repeated once if insufficient (less than 50%) reduction of CoNV should be observed (4 weeks prior to corneal transplantation at the latest). All subjects in the intervention arm will then undergo for corneal transplantation. In the control arm, subjects will be directly scheduled for corneal transplantation. Corneal transplantation will be performed as standard full-thickness penetrating procedure, and the graft (6.5 - 8.25 mm 7.75 mm in diameter) will be secured with 16-24 interrupted single or double running 10-0 nylon single sutures (decision by the surgeon). Postoperatively, follow-up assessments will be performed at 3, 6, 12, 18, and 24 months for all subjects (postoperative visits at these time points are standard of care). A slit lamp examination, concomitant medication, AE and photo documentation as well as LaserFlareCellMeter (if available), corneal tomography, SL-OCT, and corneal endothelial cell count measurements will be performed. In addition, visual acuity and a vision-related quality of life will be assessed. Macula OCT will be performed if deemed necessary. If a subject has any complaints, he or she can contact the responsible trial site at any time.

After consultation with the investigator, additional visits can be scheduled. (Protocol V04\_0 Page 50)

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Corneal Transplantation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, multicenter, open randomized parallel-group trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Corneal Crosslinking (CXL)

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)

Group Type EXPERIMENTAL

Corneal Crosslinking

Intervention Type 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)

control group

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)

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Corneal Crosslinking

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)

Intervention Type DEVICE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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

Exclusion Criteria

* \< 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
* Employees of the sponsor, or employees or relatives of the investigator.
* Pregnant women and nursing mothers as corneal transplantation in standard care is performed under general anaesthesia
* Persons held in an institution by legal or official order
* Dysregulated glaucoma with IOP \> 25 mmHg at baseline despite local therapy

(Protocol V04\_0 Page 43)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Uniklinik Köln, Zentrum für Klinische Studien

UNKNOWN

Sponsor Role collaborator

Uniklinik Köln, Institut für Medizinische Statistik und Bioinformatik

UNKNOWN

Sponsor Role collaborator

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role collaborator

Claus Cursiefen

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Claus Cursiefen

Prof. Dr.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Claus Cursiefen, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Cologne, Centre for Ophthalmology

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Augenklinik des Klinikums der Universität München

München, Bavaria, Germany

Site Status RECRUITING

University Hospital of Cologne, Centre for Ophthalmology

Cologne, North Rhine-Westphalia, Germany

Site Status RECRUITING

Universitätsklinikum Düsseldorf, Klinik für Augenheilkunde

Düsseldorf, North Rhine-Westphalia, Germany

Site Status RECRUITING

Universitätsklinikum des Saarlandes, Klinik für Augenheilkunde

Homburg, Saarland, Germany

Site Status RECRUITING

Charité - Universitätsmedizin Berlin, Klinik für Augenheilkunde

Berlin, , Germany

Site Status RECRUITING

Universitätsklinikum Freiburg, Klinik für Augenheilkunde

Freiburg im Breisgau, , Germany

Site Status RECRUITING

Klinik und Poliklinik für Augenheilkunde - Universitätsmedizin Rostock

Rostock, , Germany

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Germany

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Claus Cursiefen, Prof. Dr.

Role: CONTACT

00492214784300

Deniz Hos, Dr.

Role: CONTACT

004922147898896

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Nikolaus Luft, PD Dr. med. univ. Dr. scient.

Role: primary

0089 4400 53146

Claus Cursiefen, Professor

Role: primary

00492214780

Deniz Hos, PD Dr. med

Role: backup

004922147898896

Gerd Geerling, Univ.-Prof. Dr. med

Role: primary

004902118116051

Friedrich Anton Steindor, Dr. med

Role: backup

004902118116051

Berthold Seitz, Prof. Dr.

Role: primary

0049 6841 16-22387

Elias Flockerzi, Dr. med.

Role: backup

0049 6841 16-22387

Tina Dietrich-Ntoukas, PD Dr. med.

Role: primary

004930450654419

Anna-Karina Maier-Wenzel, PD Dr. med.

Role: backup

0049 30 450 654 419

Daniel Böhringer, Prof. Dr. med.

Role: primary

0049761 270-40235

Paola Kammrath Betancor, Dr. med.

Role: backup

0049761 270-40235

Marcus Walckling, Dr. med.

Role: primary

0049381 494 8501

Thomas A. Fuchsluger, Univ.-Prof. Dr. med. Dr. rer.

Role: backup

0049381 494 8501

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 38448965 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

01KG2127

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Uni-Koeln-5045

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

German Corneal Cross Linking Register
NCT00560651 ACTIVE_NOT_RECRUITING
Corneal Crosslinking Treatment Study
NCT04427956 COMPLETED PHASE4
McNeel Eye Center Corneal Crosslinking Study
NCT02921009 ACTIVE_NOT_RECRUITING NA