Corneal Crosslinking Treatment Study (PRICS)

Prospective Randomised Corneal Crosslinking Study

Three different protocols for inducing corneal crosslinks in subjets with progressive keratoconus will be evaluated in this randomised clinical study.

Study Overview

• Status: Completed
• Conditions: Progressive Keratoconus
• Intervention / Treatment: Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2); Drug: Isotonic riboflavin; Drug: Hypotonic riboflavin; Procedure: Iontophoresis

Detailed Description

Riboflavin does not penetrate the intact corneal epithelium. Corneal cross linking (CXL) is typically performed using the so-called "Dresden protocol". The Dresden protocol states 30 minutes of UVA-radiation (3mW/cm2) but a 10 minute irradiation protocol (9mW/cm2) is frequently used. Both of the protocols involve mechanical removal of the epithelium over the central 8 mm of the corneal surface. The first days after treatment therefore involves some degree of pain, often intense, and the presence of a healing epithelial defect may be associated with development of infiltrates in the cornea. A number of approaches have been evaluated in order to promote riboflavin penetration through the intact epithelium, of which iontophoresis appears most promising. Keratoconic corneas are thin at the cone location and sometimes it is difficult to maintain the safety margin of 400 microns during corneal crosslinking. Instead of using isotonic standard riboflavin, a swelling effect of the cornea can be obtained by using hypotonic riboflavin. However, the latter has been indicated as less effective in the process of inducing cross links.

Eighty-one of 81 patients of various degrees of keratoconus will be randomised to one of the following groups: 1) CXL (UVA 9mW/cm2) using isotonic riboflavin, or 2) CXL (UVA 9mW/cm2) using hypotonic riboflavin or 3) Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2).

Hypothesis:

i) CXL with hypotonic riboflavin or CXL with Ricrolin administered by iontophoresis or CXL with isotonic riboflavin is non-inferior compared to standard CXL with isotonic riboflavin.

ii) The morphological structure post-CXL in the three different groups will be similar without any significant differences.

The iontophoresis-assisted treatment arm has been interrupted due to low efficacy in halting disease progression. The results have been published.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Skåne
    • Lund, Skåne, Sweden, 22242
      • Skåne University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Progress in keratoconic eye. We define progress as an increase in Kmax of 1.0 diopter in 1 year or 0.5 diopter in 6 months. This increase in Kmax will be accepted as progression if concomitant changes tomographic parameters.

Exclusion Criteria:

• Concurrent ocular infection or corneal disease other than keratoconus.
• Pregnancy.
• Treatment with Isotretinoin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Isotonic riboflavin; CXL (UVA 9mW/cm2) treatment using isotonic riboflavin	Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2); CXL treatment with UVA-radiation (9mW/cm2) with a 10 minute irradiation protocol.; Drug: Isotonic riboflavin; CXL protocol with isotonic riboflavin
Active Comparator: Hypotonic riboflavin; CXL (UVA 9mW/cm2) using hypotonic riboflavin	Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2); CXL treatment with UVA-radiation (9mW/cm2) with a 10 minute irradiation protocol.; Drug: Hypotonic riboflavin; CXL protocol with hypotonic riboflavin
Active Comparator: Iontophoresis; Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2).	Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2); CXL treatment with UVA-radiation (9mW/cm2) with a 10 minute irradiation protocol.; Procedure: Iontophoresis; CXL protocol with iontophoresis and ricrolin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative change in visual acuity	Uncorrected visual acuity (UCVA) and best spectacle corrected visual acuity (BSCVA)	Patients will be evaluated 1, 6, 12 and 24 months after treatment.
Postoperative change in Kmax	Maximum corneal steepness	Patients will be evaluated 1, 6, 12 and 24 months after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative change in astigmatism	Corneal astigmatism	Patients will be evaluated 1, 6, 12 and 24 months after treatment.
postoperative change in corneal nerve cell density	Corneal nerve cell density will be evaluated using confocal microscopy	Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in Keratocyte cell density	Keratocyte cell density will be evaluated using confocal microscopy	Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in endothelial cell count	Endothelial cell count will be evaluated using confocal microscopy	Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in demarcation lines	Identification of the demarcation lines with confocal microscopy will help establishing how deep was the effect of the CXL treatment.	Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in the corneal thickness during CXL treatment	Corneal pachymetry is the process of measuring the thickness of the cornea	Corneal pachymetry will be evaluated before and then every 5 minutes during 30 minutes under CXL treatment.

Collaborators and Investigators

• Sponsor: Region Skane
• Investigators: Principal Investigator: Ingemar Gustafsson, MD, Region Skane

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2017
• Primary Completion (Actual): November 19, 2024
• Study Completion (Actual): November 19, 2024

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: corneal crosslinking
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus; Physiological Effects of Drugs; Dermatologic Agents; Micronutrients; Vitamin B Complex; Vitamins; Photosensitizing Agents; Riboflavin
• Other Study ID Numbers: DNR2015/373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No