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Trial registered on ANZCTR


Registration number
ACTRN12608000367347
Ethics application status
Not yet submitted
Date submitted
9/07/2008
Date registered
30/07/2008
Date last updated
30/07/2008
Type of registration
Prospectively registered

Titles & IDs
Public title
Collagen cross linking with riboflavin and ultraviolet A for the treatment of conical ectasia (progression) in keratoconic corneas: Analysis of clinical outcomes and micro structural changes.
Scientific title
Collagen cross linking with riboflavin and ultraviolet A for the treatment of conical ectasia (progression) in keratoconic corneas: Analysis of clinical outcomes and micro structural changes.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Keratoconus 3384 0
Condition category
Condition code
Eye 3533 3533 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The treatment aims to target the pathogenesis of keratoconus by stimulating collagen cross linking in the cornea using ultra violet light (UVA) and the photosensitiser riboflavin. The process involves stimulating covalent bonds between corneal collagen fibrils, aiming to improve the mechanical rigidity of the cornea and increase its resistance to the ectatic process.

The procedure will be conducted in a sterile procedure room in the Department of Ophthalmology, Greenlane clinical centre by a registered Ophthalmologist.

1. Eye selection based on initial work up and randomisation strategies
2. Insertion of a lid speculum
3. Instillation of tetracaine 1% and/or oxybuprocaine 0.4% in the treatment eye.
4. The central 7 mm of the cornea will be mechanically removed using a blade.
5. Instillation of riboflavin drops q. 5 mins , starting 5 mins prior to the treatment procedure (2-4 drops of 0.1% solution 10 mg riboflavin-5-phosphate in 10 mls dextran-T- 500 solution)
6. Commencement of UVA light irradiation using a UVA double diode 370 nm, located 10-12 mm in front of the corneal apex to obtain radiant energy of 3 mW/cm² or 5.4 J/ cm² (monitored via a potentiometer/ UV power metre). A Irradiation time of 5 minutes will be repeated 5 times (For a total of 30 minutes), with the lamp being switched off and instillation of the riboflavin drops between each 5 minute irradiation occurring.
7. During the procedure balanced salt solution will be instilled every 2 minutes to moisten the cornea.
8. Upon completion of the procedure the eye will be flushed with balanced salt solution.
9. Following the procedure slit lamp examination will be performed
10. A bandage contact lens will be inserted (To improve comfort for the patient while healing occurs)
11. Prophylactic broad spectrum antibiotic ointment (chloramphenicol 0.5% minims) will be instilled and dispensed to the patients.

Patients will be reviewed at day 1, 1 week, 1 month, 2 months, 3 and 6 months.
Intervention code [1] 3111 0
Treatment: Devices
Comparator / control treatment
The fellow untreated eye
Control group
Active

Outcomes
Primary outcome [1] 4438 0
Keratometry Readings (corneal curvature)
Timepoint [1] 4438 0
Day 1, 1 week, 1 month, 2 months, 3 and 6 months.
Secondary outcome [1] 7493 0
Uncorrected visual acuity
Timepoint [1] 7493 0
Day 1, 1 week, 1 month, 2 months, 3 and 6 months.

Eligibility
Key inclusion criteria
1. Patient with bilateral keratoconus

2. Patients with documented progressive keratoconus:
3. At least 2 years of follow up data available to accurately map out the rate of progression.
Classified as:
i. Increase in maximal keratometry readings over a period of up to three months
ii. change in refraction reported by patient or referring clinician, over the last 12 months (>0.75 Dioptres )
iii. Several increases of corneal keratometry readings over a period of six months (>0.75 Dioptres)
iv. Progression measured indirectly via by using rigid contact lenses of varying base curves to achieve apical clearance. Ii.e. change in documented contact lens fit in the last 6-12 months.
v. Demonstrated pachyometrical keratoconus worsening over the last six months

4. Participants must be >14 yrs of age < 30 yrs of age.

5. Maximal corneal keratometry reading of no more than 60 Dioptres

6. Minimal corneal thickness measurement of at least 400 µm

7. Preserved best spectacle corrected visual acuity of > 20/80 (6/24)

8. Clear corneas, clinically

9. Well informed patients with the ability to understand the implications of the intervention, such that they are able to consent for themselves

10. Documented rigid gas permeable contact lens intolerance
Minimum age
14 Years
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous episodes of corneal hydrops

2. Ocular surgery or trauma

3. Systemic disease which may affect cornea.

4. Demonstrated clinical topographical keratoconus stability in the last 24 months

5. Previous herpetic disease of the cornea.

6. Severe corneal dryness

7. Significant corneal desiccation staining (Grade 2 on the Cornea and Contact Lens Research Unit (CCLRU) grading scale).

8. Minimal corneal thickness of less than 400 µm

9. Evidence of sub-epithelial or mid anterior stromal scarring or opacities

10. Slit lamp examination of marked Vogt striae or confocal evidence of a deep reticular pattern of dark bands (more prone to stromal oedema and corneal haze, due to the procedure)

11. Inability to give informed consent

12. Inability to maintain repeat visits to the Ophthalmology department over a period of months

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
1. The subject will be invited into the Department of Ophthalmology’s University unit situated in the outpatient clinic of the Department of Ophthalmology, Greenlane Clinical Centre, and an explanation of the study and the procedures involved will be given using lay language. The participants will be given the opportunity to ask questions and discuss the study. Each participant will be provided with an individual study number.
A comprehensive history will be undertaken.
History:
I. Name
II. Gender
III. Date of Birth
IV. Contact details
V. Ethnic background
VI. Type of contact lens
VII. Duration of contact lens wear (years), hours per day used/ Days per week
a. (note atopy, family history, previous episodes of hydrops)
VIII. Past medical history
IX. Drug history

2. The subject will be asked to provide written informed consent.
3. A consent form and a relevant information sheet will be provided requesting permission for clinical examination of both eyes.
4. After informed consent, a medical history will be taken, followed by clinical examination using standard clinical tests, which will proceed as follows:

I. Extensive medical and ocular history
II. Uncorrected visual acuity
III. Best spectacle corrected visual acuity
IV. High and low contrast Bailey-Lovie Charts.
V. Slit-lamp biomicroscope examination confirming keratoconus diagnosis.
VI. Measurement of corneal sensitivity using a non-invasive, non-contact aesthesiometer
VII. Clinical photography on the slit-lamp biomicroscope
VIII. Corneal computerised topographical examination (Pentacam and Orbscan II)
IX. Wavefront abberometry analysis
X. Ultrasound pachymetry
XI. In vivo Confocal microscopy examination
XII. Ocular response analyser
XIII. Examination of the posterior segment (no dilating drops)

5. On the basis of these examination results, patient suitability will be assessed. Patient not meeting the required criterion will be excluded and dismissed from the study.
6. Patients who meet the criterion for the study and therefore qualify for the treatment procedure, will be scheduled an appointment time to undergo the procedure
7. A list containing study number and which eye to operate on (right or left) will be randomly generated prior to the start of the study and study numbers will be issued consecutively to subjects as they are consented. Once a study number is allocated which eye will be operated on will be looked up on the list. The untreated eye will act as the control for the study.

Collagen-cross linking procedure protocols –
The procedure will be conducted in a sterile procedure room in the Department of Ophthalmology, Greenlane clinical centre by a registered Ophthalmologist. Eye selection based on initial work up and randomisation strategies
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A list containing study number and which eye to operate on (right or left ) will be generated prior to the start of the study using simple randomisation by using a randomisation table created by a computer software and study numbers will be issued consecutively to subjects as they are consented. Once a study number is allocated which eye will be operated on will be looked up on the list.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 1036 0
New Zealand
State/province [1] 1036 0

Funding & Sponsors
Funding source category [1] 3567 0
University
Name [1] 3567 0
University of Auckland Doctoral Scholarship
Address [1] 3567 0
85 Park Rd
Grafton 1001
Auckland
Country [1] 3567 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
85 Park Rd
Grafton 1001
Auckland
Country
New Zealand
Secondary sponsor category [1] 3208 0
None
Name [1] 3208 0
Address [1] 3208 0
Country [1] 3208 0
Other collaborator category [1] 328 0
Hospital
Name [1] 328 0
Greenlane Ophthalmology Department, Auckland District Health Board
Address [1] 328 0
Building 2 Level 2
Greenlane Clinical Centre
214 Greenlane Wesst
Greenlane
Auckland
Country [1] 328 0
New Zealand

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 5609 0
Northern X Ethics Committee
Ethics committee address [1] 5609 0
3rd floor, Unisys building
650 Great South Rd
Penrose
Private Bag 92-522, Wellesley St
Aucklan
Ethics committee country [1] 5609 0
New Zealand
Date submitted for ethics approval [1] 5609 0
01/07/2008
Approval date [1] 5609 0
Ethics approval number [1] 5609 0

Summary
Brief summary
This study will investigate the changes that occur in the cornea following collagen cross linking. Recent studies have demonstrated that this procedure is effective in reducing the progression of keratoconus, however very little is known about the microstructural changes that occur during this procedure. This study aims to investigate both the clinical outcomes of this procedure (for example vision and corneal shape (topography)); as well as the cellular changes that occur in the cornea. This information will allow us to better understand the procedure and its outcomes, hence allowing us to identify the patients that are most likely to benefit.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28735 0
Address 28735 0
Country 28735 0
Phone 28735 0
Fax 28735 0
Email 28735 0
Contact person for public queries
Name 11892 0
Charlotte Jordan
Address 11892 0
Level 4
85 Park Rd
Grafton
Auckland
Country 11892 0
New Zealand
Phone 11892 0
09 3737599 Ex 84437
Fax 11892 0
Email 11892 0
c.jordan@auckland.ac.nz
Contact person for scientific queries
Name 2820 0
Charlotte Jordan
Address 2820 0
Level 4
85 Park Rd
Grafton
Auckland
Country 2820 0
New Zealand
Phone 2820 0
09 3737599 Ex 84437
Fax 2820 0
Email 2820 0
c.jordan@auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
No Results