Safety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery

• ClinicalTrials.gov Identifier: NCT01459679
• Recruitment Status: Terminated
• First Posted: October 26, 2011
• Last Update Posted: July 5, 2018
• Sponsor: American-European Congress of Ophthalmic Surgery
• Information provided by (Responsible Party): American-European Congress of Ophthalmic Surgery

Study Description

Brief Summary:

The objectives of this study are to evaluate and compare the safety and efficacy of three treatment regimens for corneal collagen cross-linking performed with VibeX (riboflavin ophthalmic solution) and the KXL System in impeding the progression of, and/or reducing maximum corneal curvature.

Condition or disease	Intervention/treatment	Phase
Keratoconus; Corneal Ectasia	Device: KXL System (15 mW/cm2); Device: KXL System (30 mW/cm2); Device: KXL System (45 mW/cm2); Drug: riboflavin ophthalmic solution	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1721 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multi-Center, Randomized, Controlled Evaluation of the Safety & Efficacy of the KXL System With VibeX (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery
• Study Start Date: July 2012
• Actual Primary Completion Date: January 2016
• Actual Study Completion Date: August 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: VibeX Treatment Group A; Corneal collagen cross-linking using riboflavin ophthalmic solution and ultraviolet-A (UVA) light for 8 minutes	Device: KXL System (15 mW/cm2); UVA irradiation for 8 minutes at 15 mW/cm2; Drug: riboflavin ophthalmic solution; Drops of riboflavin ophthalmic solution will be applied in the eye every two minutes for 20 minutes; Other Name: VibeX
Active Comparator: VibeX Treatment Group B; Corneal collagen cross-linking using riboflavin ophthalmic solution and ultraviolet-A (UVA) light for 4 minutes	Device: KXL System (30 mW/cm2); UVA irradiation for 4 minutes at 30 mW/cm2; Drug: riboflavin ophthalmic solution; Drops of riboflavin ophthalmic solution will be applied in the eye every two minutes for 20 minutes; Other Name: VibeX
Active Comparator: VibeX Treatment Group C; Corneal collagen cross-linking using riboflavin ophthalmic solution and ultraviolet-A (UVA) light for 2 minutes and 40 seconds	Device: KXL System (45 mW/cm2); UVA irradiation for 2 minutes 40 seconds at 45 mW/cm2; Drug: riboflavin ophthalmic solution; Drops of riboflavin ophthalmic solution will be applied in the eye every two minutes for 20 minutes; Other Name: VibeX

Outcome Measures

Primary Outcome Measures :

1. Mean change in maximum corneal curvature (Kmax) from baseline [ Time Frame: Month 6 or 12 ]

Secondary Outcome Measures :

1. Comparison of treatment groups within each treatment indication [ Time Frame: Month 6 and 12 ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria (all subjects):

1. Be at least 12 years of age, male or female, of any race;
2. Provide written informed consent and sign a HIPAA form. Patients who are under the age of 18 will need to sign an assent form as well as having a parent or legal guardian sign an informed consent;
3. Willingness and ability to follow all instructions and comply with schedule for follow-up visits;
4. For females capable of becoming pregnant, agree to have urine pregnancy testing performed prior to randomization of the study eye and on the day of the fellow eye treatment (which occurs between the 3 to 6 month study eye visits); must not be lactating, and must agree to use a medically acceptable form of birth control for at least one week prior to the randomization visit and continue to use the method until one month after the last dose of test article. Acceptable forms for birth control are spermicide with barrier, oral contraceptive, injectable or implantable method of contraception, transdermal contraceptive, intrauterine device, or surgical sterilization of partner. For non-sexually active females, abstinence will be considered an acceptable form of birth control. Women considered capable of becoming pregnant include all females who have experienced menarche and have not experienced menopause (as defined by amenorrhea for greater than 12 consecutive months) or have not undergone successful surgical sterilization (e.g. hysterectomy, bilateral tubal ligation, or bilateral oophorectomy);
5. BSCVA of ≥1 letter and ≤80 letters on ETDRS chart;
6. Presence of central or inferior steepening on the topographic map;
7. Contact Lens Wearers Only: Removal of contact lenses is required for a 1 week period prior to the screening visit(s);

8. Contact Lens Wearers Only: manifest refraction must be stable between two visits which occur at least 7 days apart. A stable refraction is one in which the manifest refraction spherical equivalent and the average K (Km) on the topographer taken at the first visit do not differ by more than 0.75 D from the respective measurements taken at the second exam;

   Inclusion Criteria (keratoconus subjects only):

9. Have a maximum corneal curvature as measured by Kmax of ≥ 47.00 D;

10. Having topographic evidence of keratoconus with a diagnosis of mild, moderate or severe keratoconus defined as the following:

    • Mild Keratoconus

      1. Axial topography consistent with keratoconus
      2. Flat keratometry reading ≤ 51.00 D on topography map

    • Moderate Keratoconus

      1. Axial topography consistent with keratoconus
      2. Flat keratometry reading ≥ 51.01 D and ≤ 56.00 D or astigmatism ≥ 8.00D on topography map

    • Severe Keratoconus:

      1. Axial topography consistent with keratoconus with marked areas of steepening
      2. Flat keratometry reading ≥ 56.01 D on topography map

    Inclusion Criteria (corneal ectasia subjects only):

11. Having a diagnosis of corneal ectasia after refractive surgery;
12. Having axial topography consistent with ectasia;

Exclusion Criteria (all subjects):

1. Contraindications, sensitivity or known allergy to the test article(s) or their components;
2. If female, be pregnant, nursing or planning a pregnancy or have a positive urine pregnancy test prior to the randomization or treatment of either eye or during the course of the study;
3. Corneal pachymetry that is < 375 microns prior to epithelial debridement at the thinnest point in the eye to be treated;
4. Eyes which are aphakic;
5. Eyes which are pseudophakic and do not have a UV blocking lens implanted;

6. Previous ocular condition (other than refractive error) in the eye to be treated that may predispose the eye for future complications. For example:

   1. History of corneal disease (e.g., herpes simplex, herpes zoster keratitis, recurrent erosion syndrome, corneal melt, corneal dystrophy, etc.)
   2. Clinically significant corneal scarring in the cross-linking treatment zone that is not related to keratoconus or corneal ectasia, in the investigator's opinion, will interfere with the cross-linking procedure;
7. A history of delayed epithelial healing in the eye(s) to be treated;
8. Patients with nystagmus or any other condition that would prevent a steady gaze during the treatment or other diagnostic tests;
9. Patients with a current condition that, in the investigator's opinion, would interfere with or prolong epithelial healing;
10. Taking Vitamin C (ascorbic acid) supplements within 1 week of the cross-linking treatment.
11. A history of previous corneal crosslinking treatment in the eye to be treated;
12. Have used an investigational drug or device within 30 days of the study or be concurrently enrolled in another investigational drug or device trial within 30 days of the study;
13. A history of previous corneal surgery (other than LASIK or PRK for subjects with corneal ectasia) or the insertion of Intacs in the eye(s) to be treated;
14. A history of previous Limbal Relaxing Incision (LRI) procedure in the eye(s) to be treated;

15. In addition, the Investigator may exclude or discontinue any subject for any sound medical reason;

    Exclusion Criteria (Keratoconus subjects only):

16. Eyes classified as either normal, atypical normal, or keratoconus suspect on the severity grading scheme.

Contacts and Locations

Locations

United States, Alabama

John Parker

Birmingham, Alabama, United States, 35233

United States, Arizona

Barnet Dulaney Perkins Eye Center

Phoenix, Arizona, United States, 85016

United States, California

Advanced Vision Care

Los Angeles, California, United States, 90067

Stanford University School of Medicine

Palo Alto, California, United States, 94303

Grutzmacher, Lewis and Sierra

Sacramento, California, United States, 95815

Center for Sight

Sacramento, California, United States, 95816

Newman Lasik Centers

Sacramento, California, United States, 95821

Batra Vision Medical Group

San Leandro, California, United States, 94578

Delta Eye Medical Group

Stockton, California, United States, 95207

Kaiser Permanente - Kaiser Network Patients in Northern California Only

Walnut Creek, California, United States, 94598

United States, Colorado

Mile High Corneal Specialists, PC

Denver, Colorado, United States, 80210

United States, Connecticut

Manchester Ophthalmology

Manchester, Connecticut, United States, 06040

Eye Physicians and Surgeons, PC

Milford, Connecticut, United States, 06460

United States, Florida

TLC of Miami The Laser Center of Coral Gables

Coral Gables, Florida, United States, 33134

Delray Eye Associates, PA

Delray Beach, Florida, United States, 33484

Braverman Eye Center

Hallandale Beach, Florida, United States, 33009

The Eye Institute of West Florida

Largo, Florida, United States, 33770

Herschel Lasik

Orlando, Florida, United States, 32803

LCA-Vision Inc

Tampa, Florida, United States, 33607

United States, Illinois

Quantum Vision Centers

Belleville, Illinois, United States, 62226

United States, Iowa

University of Iowa Hospitals and Clinics

Coralville, Iowa, United States, 52241

United States, Kansas

Kansas LasikPlus, P.A.

Leawood, Kansas, United States, 66211

Grene Vision Group

Wichita, Kansas, United States, 67208

United States, Kentucky

LaskiPlus Vision Center

Louisville, Kentucky, United States, 40207

United States, Louisiana

Ochsner Medical Center

New Orleans, Louisiana, United States, 70115

United States, Maine

Eyecare Medical Group

Portland, Maine, United States, 04102

United States, Maryland

GBMC Dept. of Opthalmology/Mid-Atlantic Cornea Consultants

Baltimore, Maryland, United States, 21204

Solomon Eye Physicians and Surgeons

Bowie, Maryland, United States, 20716

Eye Doctors of Washington

Chevy Chase, Maryland, United States, 20815

United States, Massachusetts

Boston Eye Group

Brookline, Massachusetts, United States, 02446

Ophthalmic Consultants of Boston

Waltham, Massachusetts, United States, 02451

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48105

Henry Ford Health System

Detroit, Michigan, United States, 48202

Verdier Eye Center P.L.C.

Grand Rapids, Michigan, United States, 49546

Michigan Cornea Consultants

Southfield, Michigan, United States, 48034

United States, Minnesota

Chu Vision Institute

Bloomington, Minnesota, United States, 55420

United States, Mississippi

Eye Surgery and Laser Center

Madison, Mississippi, United States, 39110

United States, Missouri

Pepose Vision Institute/ Lifelong Vision Foundation

Chesterfield, Missouri, United States, 63017

Ophthamology Consultants LLC

Saint Louis, Missouri, United States, 63131

United States, Montana

The Eye Clinic Surgicenter

Billings, Montana, United States, 59102

United States, Nebraska

Eye Surgical Associates

Lincoln, Nebraska, United States, 68506

Kugler Vision, PC

Omaha, Nebraska, United States, 68144

United States, Nevada

Wellish Vision Institute

Las Vegas, Nevada, United States, 89119

United States, New Jersey

Princeton Eye Group

Princeton, New Jersey, United States, 08540

United States, New Mexico

Eye Associates of New Mexico

Albuquerque, New Mexico, United States, 87109

United States, New York

CNY Eye Care

De Witt, New York, United States, 13214

North Shore LIJ Health Systems

Great Neck, New York, United States, 11021

Ramapo Ophthalmology Associates, LLP

Pomona, New York, United States, 10970

United States, North Carolina

Carolina Vision Center

Fayetteville, North Carolina, United States, 28304

United States, North Dakota

Bagan Strinden Vision

Fargo, North Dakota, United States, 58103

United States, Ohio

Comprehensive Eye Care of Central Ohio

Westerville, Ohio, United States, 43082

United States, Oklahoma

Dean McGee Eye Institute

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Devers Eye Institute

Portland, Oregon, United States, 97210

Casey Eye Institute/OHSU

Portland, Oregon, United States, 97239

United States, Pennsylvania

Ophthalmic Partners of PA, P.C.

Bala-Cynwyd, Pennsylvania, United States, 19004

Schein Ernst Eye Associates

Harrisburg, Pennsylvania, United States, 17110

Scheie Eye Institute, University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, United States, 19104

Corneal Associates, Wills Eye Institute

Philadelphia, Pennsylvania, United States, 19107

Northeastern Eye Institute

Scranton, Pennsylvania, United States, 18503

Bucci Laser Vision Institute

Wilkes-Barre, Pennsylvania, United States, 18702

United States, South Dakota

Black Hills Regional Eye Institute

Rapid City, South Dakota, United States, 57701

Wright Vision Center

Rapid City, South Dakota, United States, 57701

Vance Thompson Vision

Sioux Falls, South Dakota, United States, 57108

United States, Tennessee

Loden Vision Center

Goodlettsville, Tennessee, United States, 37072

Wang Vision Institute

Nashville, Tennessee, United States, 37203

United States, Texas

Dell Laser Consultants

Austin, Texas, United States, 78746

Buena Vista Eyecare

El Paso, Texas, United States, 79902

Eye Consultants of Texas

Grapevine, Texas, United States, 76051

Berkeley Eye Center

Houston, Texas, United States, 77027

Slade and Baker Vision Center

Houston, Texas, United States, 77027

Focal Point Vision

San Antonio, Texas, United States, 78229

United States, Utah

Hoopes Vision

Draper, Utah, United States, 84020

The Eye Institute of Utah

Salt Lake City, Utah, United States, 84107

University of Utah Dept. of Ophthalmology & Visual Sciences

Salt Lake City, Utah, United States, 84132

United States, Virginia

Silk Vision & Surgical Center

Annandale, Virginia, United States, 22003

Virginia Eye Consultants

Norfolk, Virginia, United States, 23502

Commonwealth Eye Associates

Richmond, Virginia, United States, 23238

Eye Care Center of Virginia

Richmond, Virginia, United States, 23294

Beach Eye Care

Virginia Beach, Virginia, United States, 23454

United States, Washington

Evergreen Eye Center

Federal Way, Washington, United States, 98003

United States, Wisconsin

Gundersen Clinic, Ltd.

La Crosse, Wisconsin, United States, 54601

Dean Foundation for Health, Research and Education, Inc.

Madison, Wisconsin, United States, 43715

Puerto Rico

Lilia Rivera

San Juan, Puerto Rico, 00918

Sponsors and Collaborators

American-European Congress of Ophthalmic Surgery

Investigators

• Principal Investigator: John Vukich, MD; American-European Congress of Ophthalmic Surgery

More Information

• Responsible Party: American-European Congress of Ophthalmic Surgery
• ClinicalTrials.gov Identifier: NCT01459679
• Other Study ID Numbers: ACOS-KXL-001
• First Posted: October 26, 2011
• Last Update Posted: July 5, 2018
• Last Verified: June 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Keratoconus; Corneal Diseases; Dilatation, Pathologic; Eye Diseases; Pathological Conditions, Anatomical; Riboflavin; Ophthalmic Solutions; Pharmaceutical Solutions; Vitamin B Complex; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents