Clinical trial NCT01459679: Safety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Keratoconus
Corneal Ectasia
Lead sponsor: American-European Congress of Ophthalmic Surgery
Sponsor class: NETWORK
First posted: 2011-10-26
Enrollment: 1721
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Mean change in maximum corneal curvature (Kmax) from baseline
timeFrame: Month 6 or 12
Secondary outcomes:
measure: Comparison of treatment groups within each treatment indication
timeFrame: Month 6 and 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: John Parker
state: Alabama
city: Phoenix
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Los Angeles
country: United States
facility: Advanced Vision Care
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Sacramento
country: United States
facility: Grutzmacher, Lewis and Sierra
state: California
city: Sacramento
country: United States
facility: Center for Sight
state: California
city: Sacramento
country: United States
facility: Newman Lasik Centers
state: California
city: San Leandro
country: United States
facility: Batra Vision Medical Group
state: California
city: Stockton
country: United States
facility: Delta Eye Medical Group
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente - Kaiser Network Patients in Northern California Only
state: California
city: Denver
country: United States
facility: Mile High Corneal Specialists, PC
state: Colorado
city: Manchester
country: United States
facility: Manchester Ophthalmology
state: Connecticut
city: Milford
country: United States
facility: Eye Physicians and Surgeons, PC
state: Connecticut
city: Coral Gables
country: United States
facility: TLC of Miami The Laser Center of Coral Gables
state: Florida
city: Delray Beach
country: United States
facility: Delray Eye Associates, PA
state: Florida
city: Hallandale Beach
country: United States
facility: Braverman Eye Center
state: Florida
city: Largo
country: United States
facility: The Eye Institute of West Florida
state: Florida
city: Orlando
country: United States
facility: Herschel Lasik
state: Florida
city: Tampa
country: United States
facility: LCA-Vision Inc
state: Florida
city: Belleville
country: United States
facility: Quantum Vision Centers
state: Illinois
city: Coralville
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Leawood
country: United States
facility: Kansas LasikPlus, P.A.
state: Kansas
city: Wichita
country: United States
facility: Grene Vision Group
state: Kansas
city: Louisville
country: United States
facility: LaskiPlus Vision Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Portland
country: United States
facility: Eyecare Medical Group
state: Maine
city: Baltimore
country: United States
facility: GBMC Dept. of Opthalmology/Mid-Atlantic Cornea Consultants
state: Maryland
city: Bowie
country: United States
facility: Solomon Eye Physicians and Surgeons
state: Maryland
city: Chevy Chase
country: United States
facility: Eye Doctors of Washington
state: Maryland
city: Brookline
country: United States
facility: Boston Eye Group
state: Massachusetts
city: Waltham
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Verdier Eye Center P.L.C.
state: Michigan
city: Southfield
country: United States
facility: Michigan Cornea Consultants
state: Michigan
city: Bloomington
country: United States
facility: Chu Vision Institute
state: Minnesota
city: Madison
country: United States
facility: Eye Surgery and Laser Center
state: Mississippi
city: Chesterfield
country: United States
facility: Pepose Vision Institute/ Lifelong Vision Foundation
state: Missouri
city: Saint Louis
country: United States
facility: Ophthamology Consultants LLC
state: Missouri
city: Billings
country: United States
facility: The Eye Clinic Surgicenter
state: Montana
city: Lincoln
country: United States
facility: Eye Surgical Associates
state: Nebraska
city: Omaha
country: United States
facility: Kugler Vision, PC
state: Nebraska
city: Las Vegas
country: United States
facility: Wellish Vision Institute
state: Nevada
city: Princeton
country: United States
facility: Princeton Eye Group
state: New Jersey
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico
state: New Mexico
city: De Witt
country: United States
facility: CNY Eye Care
state: New York
city: Great Neck
country: United States
facility: North Shore LIJ Health Systems
state: New York
city: Pomona
country: United States
facility: Ramapo Ophthalmology Associates, LLP
state: New York
city: Fayetteville
country: United States
facility: Carolina Vision Center
state: North Carolina
city: Fargo
country: United States
facility: Bagan Strinden Vision
state: North Dakota
city: Westerville
country: United States
facility: Comprehensive Eye Care of Central Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: Dean McGee Eye Institute
state: Oklahoma
city: Portland
country: United States
facility: Devers Eye Institute
state: Oregon
city: Portland
country: United States
facility: Casey Eye Institute/OHSU
state: Oregon
city: Bala-Cynwyd
country: United States
facility: Ophthalmic Partners of PA, P.C.
state: Pennsylvania
city: Harrisburg
country: United States
facility: Schein Ernst Eye Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Scheie Eye Institute, University of Pennsylvania School of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Corneal Associates, Wills Eye Institute
state: Pennsylvania
city: Scranton
country: United States
facility: Northeastern Eye Institute
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Bucci Laser Vision Institute
state: Pennsylvania
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Rapid City
country: United States
facility: Wright Vision Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Vance Thompson Vision
state: South Dakota
city: Goodlettsville
country: United States
facility: Loden Vision Center
state: Tennessee
city: Nashville
country: United States
facility: Wang Vision Institute
state: Tennessee
city: Austin
country: United States
facility: Dell Laser Consultants
state: Texas
city: El Paso
country: United States
facility: Buena Vista Eyecare
state: Texas
city: Grapevine
country: United States
facility: Eye Consultants of Texas
state: Texas
city: Houston
country: United States
facility: Berkeley Eye Center
state: Texas
city: Houston
country: United States
facility: Slade and Baker Vision Center
state: Texas
city: San Antonio
country: United States
facility: Focal Point Vision
state: Texas
city: Draper
country: United States
facility: Hoopes Vision
state: Utah
city: Salt Lake City
country: United States
facility: The Eye Institute of Utah
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Dept. of Ophthalmology & Visual Sciences
state: Utah
city: Annandale
country: United States
facility: Silk Vision & Surgical Center
state: Virginia
city: Norfolk
country: United States
facility: Virginia Eye Consultants
state: Virginia
city: Richmond
country: United States
facility: Commonwealth Eye Associates
state: Virginia
city: Richmond
country: United States
facility: Eye Care Center of Virginia
state: Virginia
city: Virginia Beach
country: United States
facility: Beach Eye Care
state: Virginia
city: Federal Way
country: United States
facility: Evergreen Eye Center
state: Washington
city: La Crosse
country: United States
facility: Gundersen Clinic, Ltd.
state: Wisconsin
city: Madison
country: United States
facility: Dean Foundation for Health, Research and Education, Inc.
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: Lilia Rivera
Study officials:
affiliation: American-European Congress of Ophthalmic Surgery
name: John Vukich, MD
role: PRINCIPAL_INVESTIGATOR
References: