Corneal Collagen Crosslinking for Progressive Keratoconus and Ectasia Using Riboflavin/Dextran and Hypotonic Riboflavin - Full Text View

Sponsor:	Cornea and Laser Eye Institute
Information provided by (Responsible Party):	Cornea and Laser Eye Institute
ClinicalTrials.gov Identifier:	NCT01152541

Purpose

Corneal collagen crosslinking (CXL) has been proposed as an effective method of reducing progression of both keratoconus and corneal ectasia after surgery, as well as possibly decreasing the steepness of the cornea in these pathologies. During the CXL procedure, the central corneal thickness has been shown to significantly change. The investigator's believe that better maintenance of corneal thickness potentially could have benefits of better reproducibility of the crosslinking effect with improved predictability of results.

Condition	Intervention	Phase
Keratoconus Corneal Ectasia	Drug: Riboflavin/Dextran Drug: Hypotonic Riboflavin	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Corneal Collagen Crosslinking for Progressive Keratoconus and Ectasia Using Riboflavin/Dextran and Hypotonic Riboflavin

Resource links provided by NLM:

MedlinePlus related topics: Corneal Disorders

Drug Information available for: Riboflavin Dextrans

U.S. FDA Resources

Further study details as provided by Cornea and Laser Eye Institute:

Primary Outcome Measures:

Corneal thickness [ Time Frame: Intraoperatively ] [ Designated as safety issue: No ]
Changes in central pachymetry (as measured by ultrasound) measured intraoperatively will be compared to a baseline preoperative value. Thickness will also be assessed at 1, 3, 6 and 12 months postoperatively.

Secondary Outcome Measures:

Maximum Keratometry [ Time Frame: 12 months ] [ Designated as safety issue: No ]
The change in maximum keratometry (Kmax) from baseline will be evaluated at 12 months for all eyes randomized to (Group 1 - administration of Riboflavin/dextran for the duration of UV exposure.) and (Group 2 - Administration of hypotonic riboflavin for the duration of UV exposure) groups. As a secondary analysis of this endpoint, the change in maximum keratometry (Kmax) from baseline will be evaluated at 1, 3 and 6 month for all eyes
Manifest Refraction [ Time Frame: 12 months ] [ Designated as safety issue: No ]
The change in manifest refraction spherical equivalent from baseline will be evaluated at 12 months. As a secondary analysis of this endpoint, a repeated measures analysis of variance will be conducted to assess the profile of the treatments across time at 1 month for the treatment groups as well as at 3, and 6 months to look at the effect of CXL timing on this variable.
Visual Acuity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Change in BSCVA (best spectacle corrected visual acuity) and UCVA (uncorrected visual acuity) compared to the baseline examination will be evaluated at 12 months postoperatively. As a secondary analysis of this endpoint will be conducted to assess the profile of the treatments across time at 1 month and again at 3, and 6 months following the CXL procedure.
Endothelial Cell Density [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Endothelial cell count will be obtained using specular microscopy (Konan Medical) prior to CXL treatment and at 12 months postoperatively. Measurements will also be taken 3 months postoperatively and compared to baseline values.

Estimated Enrollment:	160
Study Start Date:	June 2010
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Hypotonic Riboflavin Administration of hypotonic riboflavin every 2 minutes for the duration of UV exposure.	Drug: Hypotonic Riboflavin Administration of hypotonic riboflavin every 2 minutes for the duration of UV exposure. Other Name: Hypotonic (low salt) riboflavin solution without dextran
Active Comparator: Riboflavin/dextran Administration of Riboflavin/dextran every 2 minutes for the duration of UV exposure.	Drug: Riboflavin/Dextran Administration of riboflavin/dextran every 2 minutes for the duration of UV exposure Other Name: Riboflavin in a dextran solution

Detailed Description:

The objective of this study is to investigate the difference between the two riboflavin preparations during UV (ultraviolet) administration. Both riboflavin preparations currently are in general use worldwide and in U.S. clinical trials of corneal collagen crosslinking. The first preparation contains riboflavin in a dextran solution, which may tend to dehydrate the cornea and keep it thinner. The second preparation contains riboflavin in a solution without dextran; in this case, the relative hypotonicity may tend to keep the cornea better hydrated and thicker. The primary goal of the study is to see if the use of hypotonic riboflavin (rather than riboflavin with dextran) better maintains consistent corneal thickness during the CXL procedure. The second goal of the study is to determine if better maintenance of corneal thickness potentially could have benefits of better consistency of the procedure, decrease in corneal haze formation, and improved safety of the endothelial cells. Safety and efficacy outcomes will then be compared between the groups. In particular, we will compare the corneal thickness measured by ultrasonic pachymetry immediately after the CXL procedure in the randomized eyes. Secondary outcomes will include visual acuity, longer term corneal thickness changes, and corneal steepness changes. Safety assessments will include a tabulation of adverse events, patient symptoms, loss of visual acuity, changes in endothelial cell density, slit lamp examination of the cornea and lens, and contact lens tolerance for contact lens wearers

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

18 years of age or older
A diagnosis of progressive keratoconus over a period of 24 months or less before randomization or a diagnosis of corneal ectasia after corneal refractive surgery
Vision with contact lenses or glasses is worse than 20/20
Corneal thickness greater than 300 microns at the thinnest point

Exclusion Criteria:

Eyes classified as either normal, atypical normal, or keratoconus suspect on the severity grading scheme.
Corneal pachymetry ≤ 300 microns at the thinnest point measured by Pentacam in the eye(s) to be treated.
Previous ocular condition (other than refractive error) in the eye(s) to be treated that may predispose the eye for future complications
Clinically significant corneal scarring in the CXL treatment zone
Pregnancy (including plan to become pregnant) or lactation during the course of the study
A known sensitivity to study medications
Patients with nystagmus or any other condition that would prevent a steady gaze during the CXL treatment or other diagnostic tests.
Patients with a current condition that, in the investigator's opinion, would interfere with or prolong epithelial healing.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01152541

Contacts

Contact: Stacey Lazar

201-833-0505

info@vision-institute.com

Locations

United States, New Jersey
Cornea and Laser Eye Institute	Recruiting
Teaneck, New Jersey, United States, 07666
Contact: Stacey Lazar 201-883-0505 info@vision-institute.com
Principal Investigator: Peter Hersh, MD

Sponsors and Collaborators

Cornea and Laser Eye Institute

Investigators

Principal Investigator:

Peter Hersh, MD

Cornea and Laser Eye Institute

More Information

No publications provided

Responsible Party:	Cornea and Laser Eye Institute
ClinicalTrials.gov Identifier:	NCT01152541 History of Changes
Other Study ID Numbers:	HYPO-CXL-001
Study First Received:	June 22, 2010
Last Updated:	November 1, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Cornea and Laser Eye Institute:

Keratoconus
Corneal Ectasia
Collagen Crosslinking
Riboflavin

Additional relevant MeSH terms:

Dilatation, Pathologic
Keratoconus
Corneal Diseases
Pathological Conditions, Anatomical
Eye Diseases
Dextrans
Riboflavin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

Plasma Substitutes
Blood Substitutes
Photosensitizing Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Dermatologic Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on February 09, 2012