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Trial registered on ANZCTR


Registration number
ACTRN12609000320257
Ethics application status
Not yet submitted
Date submitted
20/04/2009
Date registered
21/05/2009
Date last updated
21/05/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Randomised, prospective, double-masked, vehicle-controlled study to evaluate the safety and efficacy of topical Nexagon(registered trademark) in subjects with ocular surface chemical burns.
Scientific title
Randomised, prospective, double-masked, vehicle-controlled study to evaluate the safety and efficacy of topical Nexagon (registered trademark) in subjects with ocular surface chemical burns.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ocular chemical injury 4632 0
Condition category
Condition code
Eye 4933 4933 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nexagon (registered trademark) - a topical preparation of DNA (Deoxyribonucleic Acid) oligonucleotide molecule that blocks specifically the translation of connexin 43, of which is the building block of one type of gap junctions (cell to cell communication channel).

We will be conducting the trial with a topical agent in a gel formulation. Upon entry in to the main part of the study, all patients will be assessed for severity of their ocular injury to determine the standard of care treatment regimen that will be initiated prior to the first addition of the study treatment – either Nexagon(registered trademark) or Nexagon (registered trademark) vehicle as placebo. This will be double-masked to both the patient and the treating clinicians.
Treatments: Study treatment is given in two parts over Day 1 and Day 2. Part one involves application of study treatment in a 14mm carrier soft (silicon hydrogel) contact lens with a standard dose of 10micrograms/50microlitres of Nexagon (registered trademark) or Nexagon (registered trademark) vehicle. This will stay in for the duration one hour, and then removed. Study treatment is applied again as 6micrograms/100microlitres Nexagon (registered trademark) or Nexagon (registered trademark) vehicle in divided doses over the upper and lower fornices of the affected eye. If the participants fall in the moderate/severe group, they will have again received the standard treatment prior to the second application of Nexagon (registered trademark) or Nexagon (registered trademark) vehicle. Application of the study treatment occurs again on day 2, where the same steps are repeated. If clinically indicated, the severely injured eyes may require amniotic membrane transplant. These patients will then receive a third dose (10micrograms/50microlitres) of study treatment under the transplanted amnion.

Other wise, no further application of the trial treatment will be given.
Intervention code [1] 4391 0
Treatment: Drugs
Comparator / control treatment
Control of this study is the vehicle medium of Nexagon (registered trademark). It is a gelling agent called Poloxamer 407, and is a common ingredient in pharmaceutical and many other products. Poloxamer 407 is a hydrophilic non-ionic surfactant of the more general class of copolymers known as poloxamers. Poloxamer 407 is a triblock copolymer consisting of a central hydrophobic block of polypropylene glycol flanked by two hydrophilic blocks of polyethylene glycol.
Application of the control group will not be any different to the treatment group.
Control group
Placebo

Outcomes
Primary outcome [1] 5780 0
Percentage reduction in corneal epithelial defect from baseline to Day 5 in the study eye.

The dimensions of the residual epithelial defects will be measured during clinical assessment with the slit lamp bio-microscopy by the researching clinician. Digital photos will also be taken and the area of the defect calculated with the well recognised medical statistical programme, ImageJ.
Timepoint [1] 5780 0
Day 5 of the initial ocular chemical injury.
Secondary outcome [1] 242088 0
1.1 Time to complete corneal re-epithelialisation of the study eye.
Timepoint [1] 242088 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [2] 242089 0
1.2 Percentage and rate of reduction in corneal epithelial defect from baseline to subsequent visits.
Timepoint [2] 242089 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [3] 242090 0
1.3 Degree of residual corneal haze and progression.
Timepoint [3] 242090 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [4] 242091 0
1.4 Incidence and extent (percentage of original cornea wound area) of conjunctival epithelialisation of cornea as assessed by confocal microscopy.
Timepoint [4] 242091 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [5] 242092 0
1.5 Corneal topography (by Pentacam) to assess surface irregularity and corneal thickness after recovery from injury.
Timepoint [5] 242092 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [6] 242093 0
2.1 Time to complete conjunctival re-epithelialisation of the study eye.
Timepoint [6] 242093 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [7] 242094 0
2.2 Percentage and rate of reduction in conjunctival epithelial defect from baseline to subsequent visits.
Timepoint [7] 242094 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [8] 242095 0
2.3 Rate of reduction of inflammation from baseline to subsequent visits.
Timepoint [8] 242095 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [9] 242096 0
2.4 Incidences and severity of conjunctival scarring and formation of symblepharon.
Timepoint [9] 242096 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [10] 242097 0
3.1 Percentage and rate of limbal reperfusion change from baseline to subsequent visits.
Timepoint [10] 242097 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.
Secondary outcome [11] 242098 0
4.1 Final visual acuity and rate of recovery of both high and low contrast (at 10%) visual acuity measured with EDTRS (Early Treatment Diabetic Retinopathy Study) chart.
Timepoint [11] 242098 0
Depending on severity, participants may either be admitted or followed up on an outpatient basis. All participants are reviewed daily for the first 14 days, where everyone has slit lamp bio-microscopy examination with photography in the Acute Eye Clinic. Thereafter, participants are seen every two days for one week then weekly for further one month. Further reviews will be scheduled on Day 60 and 90. Follow-up reviews for those participants who received an amniotic membrane transplant will take a different course with further spaced out reviews. A standardised assessment form plus photographic documentation shall be carried out where possible by the same clinician. We aim to continue follow up until complete recovery of the injury or on Day 90. We also aim to have a one year recall to follow-up progression of healing and any changes to the participant?s visual acuity.

Eligibility
Key inclusion criteria
1. Ocular chemical injury with limbal involvement.

2. Subjects with ocular chemical burns within the last 12 hours.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subjects with very mild ocular chemical burns – i.e., those classified as Grade I on the classification system by Dua et al.

2. Subjects presenting with ocular chemical burns ted more than 12 hours after the incident.

3. Subjects who have previously had corneal surgery.

4. Subjects with bilateral ocular surface involvement will have the less injured eye excluded from the study.

5. Subjects with any pre-existing ocular disease or corneal abnormality (complete list in study protocol).

6. Subjects who require any systemic medication that affects healing, e.g., steroids, hormone replacement therapy.

7. Subjects who are taking amiodarone, long acting anticholinergics, e.g., atropine, scopolamine, or medications or agents that can cause dry eye.

8. Subjects who have participated in a clinical trial within the 30 days prior to the date of the chemical injury.

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)
Eligible patients will be recruited from Greenlane Clinical Centre, through the Ophthalmology Acute Eye Clinic. Those who meet the inclusion and exclusion criteria, who agree to take part in the study, and who have read, understood and signed the patient consent form, will be invited to take part in this study.

Allocation of the treatment/placebo groups are done by double-blinded randomisation. The treating clinician will receive treatment containers separated into 2 main groups mild and moderate/severe; severity stratified. These containers will be labeled with sequential numbers and will contain 50% of Nexagon (registered trademark) and 50% Nexagon vehicle. The content will not be identifiable to the treating clinician and he or she will just follow the sequential number in the severity group that the participants fall in. An independent person from the manufacturer and the statistician will hold the allocation code.

We aim to treat up to 66 patients.
We set out to start with a safety sub-study. The first 6 participants recruited will be involved in a small, open-labeled study where all participants in addition to standard of care treatment determined by the severity of their ocular injury will receive Nexagon (registered trademark) at the dose proposed for the subsequent double-masked phase of the study.
The recruitment of the remaining 60 participants will be severity stratified and we aim to have 30 participants in the mild group and 30 in the moderate/severe group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Method of randomisation for this study will be stratified block randomisation with a 1:1 ratio Nexagon (registered trademark) : Nexagon Vehicle.

There will only be one stratification factor used in the randomisation which will be severity score (mild, moderate, and severe).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/05/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment outside Australia
Country [1] 1736 0
New Zealand
State/province [1] 1736 0
Auckland

Funding & Sponsors
Funding source category [1] 4813 0
University
Name [1] 4813 0
University of Auckland
Country [1] 4813 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Department ot Ophthalmology, Faculty of Medicine and Health Sciences, The University of Auckland.
Private Bag 92019, Auckland 1023, NZ
Country
New Zealand
Secondary sponsor category [1] 4346 0
None
Name [1] 4346 0
Address [1] 4346 0
Country [1] 4346 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 6858 0
Northen X Regional Ethics Committee
Ethics committee address [1] 6858 0
Ethics committee country [1] 6858 0
New Zealand
Date submitted for ethics approval [1] 6858 0
23/03/2009
Approval date [1] 6858 0
Ethics approval number [1] 6858 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29511 0
Address 29511 0
Country 29511 0
Phone 29511 0
Fax 29511 0
Email 29511 0
Contact person for public queries
Name 12758 0
Chi-Ying Chou
Address 12758 0
Department ot Ophthalmology, Faculty of Medicine and Health Sciences, The University of Auckland.
Private Bag 92019, Auckland 1023, NZ
Country 12758 0
New Zealand
Phone 12758 0
+64 9 373 7599 Ext 83803
Fax 12758 0
Email 12758 0
c.chou@auckland.ac.nz
Contact person for scientific queries
Name 3686 0
Chi-Ying Chou
Address 3686 0
Department ot Ophthalmology, Faculty of Medicine and Health Sciences, The University of Auckland.
Private Bag 92019, Auckland 1023, NZ
Country 3686 0
New Zealand
Phone 3686 0
+64 9 373 7599 Ext 83803
Fax 3686 0
Email 3686 0
c.chou@auckland.ac.nz

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No Supporting Document Provided



Results publications and other study-related documents

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