NCT04532788

Brief Summary

The standard or Dresden protocol was established in 2003 and treats the entire cornea. However, recent ultra-structural research showed that keratoconus is localized. Therefore, treating only the affected zone and minimalizing the risk of damaging surrounding tissues would be beneficial. The objective of this study is to evaluate whether the effectiveness of customized cross-linking (cCXL) is non-inferior to standard accelerated cross-linking (sCXL) in terms of flattening of the cornea and halting keratoconus progression.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
124

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Mar 2021

Longer than P75 for not_applicable

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 20, 2020

Completed
11 days until next milestone

First Posted

Study publicly available on registry

August 31, 2020

Completed
6 months until next milestone

Study Start

First participant enrolled

March 1, 2021

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2024

Completed
4 days until next milestone

Study Completion

Last participant's last visit for all outcomes

June 5, 2024

Completed
Last Updated

June 11, 2024

Status Verified

March 1, 2023

Enrollment Period

3.3 years

First QC Date

August 20, 2020

Last Update Submit

June 10, 2024

Conditions

Keratoconus

Keywords

KeratoconusCrosslinkingCustomized

Outcome Measures

Primary Outcomes (1)

  • Change in maximum keratometry (Kmax)

    Kmax is measured with Scheimpflug photography (Pentacam® HR, OCULUS Optikgeraete GmbH, Wetzlar, Germany)

    12 months postoperatively

Secondary Outcomes (22)

  • Visual acuity

    at baseline, 4 weeks, 3 months, 6 months and 12 months postoperatively

  • Refraction

    at baseline and 12 months postoperatively

  • Depth and size of demarcation line

    at 4 weeks and 12 months postoperatively

  • Pachymetry

    at baseline, 4 weeks, 3 months, 6 months and 12 months postoperatively

  • Zonal Kmax

    at baseline, 4 weeks, 3 months, 6 months and 12 months postoperatively

  • +17 more secondary outcomes

Study Arms (2)

Customized crosslinking

ACTIVE COMPARATOR

In the customized corneal cross-linking protocol (cCXL) a patient-specific treatment pattern, based on the patient's Pentacam images, will be used to treat the cornea. The CXL pattern exists out of 3 concentric circles and is centered on the cone. To estimate the cone location a combination of the thinnest corneal point, maximum anterior elevation and maximum posterior elevation is used. The epithelium is debrided with alcohol within the marked zone. After the application of riboflavin each circle receives a different amount of energy, which gradually decreases with increasing circle size. The procedure is done with the Avedro Mosaic CXL device (Avedro, Inc. Waltham, Massachusetts, United States).

Procedure: Customized crosslinking

Standard crosslinking

ACTIVE COMPARATOR

In the standard corneal cross-linking protocol (sCXL) the epithelium is debrided with alcohol over a region with a diameter of 9.0 mm. After the application of riboflavin the cornea is irradiated with UVA with a fluence of 10 mW/cm2 during 9 minutes with a diameter of 9.0 mm, resulting in a total energy of 5.4 J/cm2. The procedure is done with the Avedro Mosaic CXL device (Avedro, Inc. Waltham, Massachusetts, United States).

Procedure: Standard crosslinking

Interventions

Customized crosslinkingPROCEDURE

In the customized corneal cross-linking protocol (cCXL) a patient-specific treatment pattern, based on the patient's Pentacam images, will be used to treat the cornea. The CXL pattern exists out of 3 concentric circles and is centered on the cone. To estimate the cone location a combination of the thinnest corneal point, maximum anterior elevation and maximum posterior elevation is used. The epithelium is debrided with alcohol within the marked zone. After the application of riboflavin each circle receives a different amount of energy, which gradually decreases with increasing circle size. The procedure is done with the Avedro Mosaic CXL device (Avedro, Inc. Waltham, Massachusetts, United States).

Customized crosslinking
Standard crosslinkingPROCEDURE

In the standard corneal cross-linking protocol (sCXL) the epithelium is debrided with alcohol over a region with a diameter of 9.0 mm. After the application of riboflavin the cornea is irradiated with UVA with a fluence of 10 mW/cm2 during 9 minutes with a diameter of 9.0 mm, resulting in a total energy of 5.4 J/cm2. The procedure is done with the Avedro Mosaic CXL device (Avedro, Inc. Waltham, Massachusetts, United States).

Standard crosslinking

Eligibility Criteria

Age16 Years - 45 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Progressive keratoconus based on an increase of maximum keratometry (Kmax) of 1 diopter (D) over a time period of 12 months

You may not qualify if:

  • Corneal scarring
  • Corneal disease other than keratoconus
  • History of corneal surgery (e.g. refractive surgery, corneal transplantation, intracorneal ring segments)
  • Patient unwilling or unable to give informed consent, unwilling to accept randomization or inability to complete follow-up (e.g. hospital visits) or comply with study procedures
  • Insufficient corneal thickness including epithelium \< 375 µm
  • Pregnancy
  • Among patients in whom both eyes are eligible only the first eye which is undergoing corneal cross-linking is enrolled in the study
  • Participation in another clinical study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Maastricht University Medical Center (MUMC+)

Maastricht, Limburg, 6229 HX, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (1)

  • Vandevenne MMS, Berendschot TTJM, Winkens B, van den Biggelaar FJHM, Visser N, Dickman MM, Wisse RPL, Wijdh RHJ, Roy AS, Shetty R, Nuijts RMMA. Efficacy of customized corneal crosslinking versus standard corneal crosslinking in patients with progressive keratoconus (C-CROSS study): study protocol for a randomized controlled trial. BMC Ophthalmol. 2023 May 19;23(1):224. doi: 10.1186/s12886-023-02976-4.

    PMID: 37208674DERIVED

MeSH Terms

Conditions

Keratoconus

Condition Hierarchy (Ancestors)

Corneal DiseasesEye Diseases

Study Officials

  • R.M.M.A. Nuijts, MD, PhD

    Department of Ophthalmology, Maastricht University Medical Center (MUMC+)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 20, 2020

First Posted

August 31, 2020

Study Start

March 1, 2021

Primary Completion

June 1, 2024

Study Completion

June 5, 2024

Last Updated

June 11, 2024

Record last verified: 2023-03

Locations

NL(3)