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Trial registered on ANZCTR


Registration number
ACTRN12612000055808
Ethics application status
Approved
Date submitted
11/01/2012
Date registered
11/01/2012
Date last updated
4/05/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Corticosteroid eye-drops for bacterial keratitis
Scientific title
Efficacy and safety of topical corticosteroid compared to placebo in the treatment of bacterial keratitis
Secondary ID [1] 273397 0
Nil
Universal Trial Number (UTN)
U1111-1125-8369
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bacterial keratitis 279175 0
Condition category
Condition code
Eye 279373 279373 0 0
Diseases / disorders of the eye
Infection 285735 285735 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Topical corticosteroid prednisolone acetate 1.0% (one eyedrop four times daily for three weeks).

Intervention and control study arms will also receive topical ciprofloxacin 0.3% (antibiotic) one drop hourly during waking hours for the first 48 hours, then 2 hourly during waking hours until re-epithelialisation, then four times daily whilst using the study drug (three weeks).

Study medication will be introduced on day 4 of treatment with at least two days of progressive corneal improvement and will be administered four times a day for three weeks until a study endpoint has occurred (e.g. healing, worsening).

If participants have a bacterial strain resistant to ciprofloxacin, as per usual management, treatment with another suitable topical antibiotic will be instigated.
Intervention code [1] 283731 0
Treatment: Drugs
Comparator / control treatment
Identical placebo (one eyedrop four times daily for three weeks).

Intervention and control study arms will also receive topical ciprofloxacin 0.3% (antibiotic) one drop hourly during waking hours for the first 48 hours, then 2 hourly during waking hours until re-epithelialisation, then four times daily whilst using the study drug (three weeks).

Study medication will be introduced on day 4 of treatment with at least two days of progressive corneal improvement and will be administered four times a day for three weeks until a study endpoint has occurred (e.g. healing, worsening).

If participants have a bacterial strain resistant to ciprofloxacin, as per usual management, treatment with another suitable topical antibiotic will be instigated.
Control group
Placebo

Outcomes
Primary outcome [1] 285963 0
Time to corneal healing (re-epithelisation).

This outcome will be assessed by slit lamp examination of the cornea with topical fluoroscein dye, and anterior chamber optical coherence tomography (OCT), which will allow exact measurements of the corneal lesion to be recorded
Timepoint [1] 285963 0
Baseline, and at 4, 7, 14, 21 and 90 days following study enrolment
Secondary outcome [1] 294858 0
Symptom resolution as assessed by composite score summerizing key symptoms (1=mild to 10=severe) of following six feature; pain, foreign body sensation, epiphoria, photophobia, reduced vision and ocular discharge.
Timepoint [1] 294858 0
4, 7, 14, 21 and 90 days following study enrolment
Secondary outcome [2] 294859 0
Visual acuity.

Best corrected visual acuity with be recorded with a LogMAR Chart.
Timepoint [2] 294859 0
Baseline, and at 4, 7, 14, 21 and 90 days following study enrolment
Secondary outcome [3] 294860 0
Adverse effects of treatment (ocular and non ocular) (e.g. temporary stinging, blurred vision, allergic reaction, delayed wound healing or red eye. The following adverse effects may occur with patients on long term steroid eye-drops, but are rarely seen with short term (three weeks) treatments. These include an increase in intraocular pressure, increased risk of cataract formation, scleral or corneal perforation, anterior uveitis, dilated pupil, loss of accommodation, ptosis, headache, and altered taste.

Paticipants will be monitored for adverse effects by assessment and slit lamp examination during each visit
Timepoint [3] 294860 0
4, 7, 14, 21 and 90 days following study enrolment
Secondary outcome [4] 294861 0
Serious complications of infection (e.g. corneal perforation, corneal scarring, endophthalmitis).

Possible complications of infection will be assessed at each vists with slit lamp and anterior chamber OCT examination.
Timepoint [4] 294861 0
4, 7, 14, 21 and 90 days following study enrolment
Secondary outcome [5] 294862 0
Computerised corneal topography
Timepoint [5] 294862 0
Baseline and at 4, 7, 14, 21 and 90 days following study enrolment

Eligibility
Key inclusion criteria
Diagnosis of culture postivie bacterial keratitis, corneal defect less than or equal to 1.5mm and not within 1.0mm of the limbus, aged 16 or over, topical antibiotic given for at least three days with signs of clinical improvement.
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Corneal perforation or impending perforation, descemetocele or endophthalmitis, evidence of herptic keratitis, fungal, or acanthambeoba infection by exam or history, pre-existing corneal scar, use of topical steriod in affected eye or systemic corticosteriod during course of present infection, aged under 16 years, bilateral corneal infections, previous penetrating corneal transplant, pregnancy, best corrected vision worse than 6/60 in fellow eye, allergy to study drugs, uncontrolled systemic disease, concurrent ocular infections and patients requiring treatment with subconjuctival injection.

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)
Patients will be given the opportunity to participate in the study following diagnosis of bacterial keratitis in our acute eye clinic. Consenting patients will be allocated to concealed groups coded by an independent organisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Consenting patients will be randomised by computer generated code in blocks to either study group by an independent organisation outside University of Auckland
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
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] 3951 0
New Zealand
State/province [1] 3951 0

Funding & Sponsors
Funding source category [1] 284220 0
University
Name [1] 284220 0
University of Auckland
Address [1] 284220 0
Department of Ophthalmology
Faculty of Medical and Health Sciences
Private Bag 92019
Auckland 1142
New Zealand
Country [1] 284220 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Department of Ophthalmology
Faculty of Medical and Health Sciences
Private Bag 92019
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 269175 0
None
Name [1] 269175 0
Address [1] 269175 0
Country [1] 269175 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286180 0
Northern X Regional Ethics Committee
Ethics committee address [1] 286180 0
Private Bag 92522
Wellesley Street
Auckland 1141
Ethics committee country [1] 286180 0
New Zealand
Date submitted for ethics approval [1] 286180 0
25/11/2011
Approval date [1] 286180 0
07/02/2012
Ethics approval number [1] 286180 0
NTX/11/12/120

Summary
Brief summary
Bacterial keratitis (bacterial infection of the cornea) can cause permanent scarring of the cornea resulting in visual loss possibly requiring corneal transplant. Scarring is caused in large part by the infection but also by the body’s immune/inflammatory response to infection with subsequent opacification of the cornea. It is thought that suppressing the immune/inflammatory response through the use of topical corticosteroid will reduce the incidence of permanent corneal scarring and minimise visual loss. The proposed study will be randomised, placebo controlled, and double-masked. All participants will remain on topical antibiotics throughout the study; in addition, one group will receive corticosteroid eye-drops, the other an identical placebo eye-drop. Neither the patients nor the investigators will know which treatment is being used until results have been analysed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33397 0
Address 33397 0
Country 33397 0
Phone 33397 0
Fax 33397 0
Email 33397 0
Contact person for public queries
Name 16644 0
Elissa McDonald
Address 16644 0
Department of Ophthalmology
Faculty of Medical and Health Sciences
Private Bag 92019
Auckland 1142
New Zealand
Country 16644 0
New Zealand
Phone 16644 0
+64 9 3737599 extn 84437
Fax 16644 0
Email 16644 0
elissa.mcdonald@auckland.ac.nz
Contact person for scientific queries
Name 7572 0
Elissa McDonald
Address 7572 0
Department of Ophthalmology
Faculty of Medical and Health Sciences
Private Bag 92019
Auckland 1142
New Zealand
Country 7572 0
New Zealand
Phone 7572 0
+64 9 3737599 extn 84437
Fax 7572 0
Email 7572 0
elissa.mcdonald@auckland.ac.nz

No data has been provided for results reporting
Summary results
Not applicable