Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03763006 |
| Other study ID # |
R1451/34/2017 |
| Secondary ID |
2017/2387 |
| Status |
Completed |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2018 |
| Est. completion date |
April 1, 2019 |
Study information
| Verified date |
December 2018 |
| Source |
Singapore National Eye Centre |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The use of povidone iodine solution for prophylaxis of endophthalmitis is well established
for intraocular procedures like cataract surgery and for injections of anti-VEGF agents for
retinal diseases such as age-related macular degeneration. Unfortunately iodine is unfriendly
to the ocular surface, and when repeated often enough (some patients require up to monthly
injections of anti-VEGF agents for the entire year), corneal epitheliopathy and secondary dry
eye results. Unfortunately, there is no good alternative to cleaning patient's eyelid at the
moment. Ocudox is a relatively new antibacterial product (spraying on eyelid wipe) which
contains Neutrox (pure hypochlorous acid) that kills many microbes, but remain very friendly
and non-toxic for the ocular surface.
Description:
In a multicentre study involving 71 eyes, reported at a conference abstract (ARVO), Avenova
(similar ingredients as Ocudox) reduces bacteria on ocular skin surface by more than 90%
without altering the diversity of bacteria on the ocular skin surface in any significant way.
This lowering of the bacterial load was particularly noteworthy for all staphylococci,
including S. epidermidis, the most frequently recovered species. At 20 minutes following
treatment, 138 unique bacterial strains belonging to 26 different species were recovered.
However, the efficacy of anti-microbial action has not been compared to the gold standard of
a single wipe with povidone iodine solution. Investigator intend to compare pre and post
treatment of Ocudox and a single use of povidine iodine solution at Day 14 in terms of the
alteration of the conjunctival microbiome of the eye and the effect on the ocular surface.
Clinical significance The study has implications on the prophylaxis of infection in many
common ophthalmic procedures conducted in Singapore National Eye Centre and many places in
the world.
1. OBJECTIVES The aim of this study is to compare pre and post-treatment of the application
of Ocudox to a single use of povidine iodine solution at Day 14in terms of the
alteration of the conjunctival microbiome and the integrity of the eye.
2. EXPECTED RIKS AND BENEFITS There would be no expected risk involved as all the
evaluations are non-invasive. However, there will be some slight discomfort from measure
tear volume or tear collection (Schirmer's strips) and also slight discomfort from
culturing procedure.
There are no known benefits from participation in this study. However, this project may have
the potential to prevent infection in many common ophthalmic procedures conducted in
Singapore National Eye Centre and many places in the world.
3. STUDY POPULATION 3.1. List the number and nature of subjects to be enrolled. Due to the
nature of the preliminary study, six participants with Meibomian Gland Dysfunction (MGD) will
be recruited from Singapore National Eye Centre. Participants will be randomised into either
Ocudox group or single use povidine iodine solution.
n= 3 (Ocudox group) n= 3 (Single use povidine iodine solution)
3.2. Criteria for Recruitment and Recruitment Process
1. Participants meet all the inclusion criteria listed below. 2. Clear of exclusion criteria.
Permission would be sought from the attending doctors before participants are being
recruited.
Eligible participants will be counselled on the study by the study coordinator. If the
participant is interested, the study coordinator will then accompany the participant to SERI
level 5 for the relevant assessments. Informed written consent will be obtained from all
participants.
3.3. Inclusion Criteria Participants must meet all of the inclusion criteria to participate
in this study.
1. Participants must be 50 to 60 years old with Meibomian Gland Dysfunction (MGD) 2. Clear of
exclusion criteria 3. Willing to perform all eye examinations in this study 3.4. Exclusion
Criteria Participants meeting any of the exclusion criteria will be excluded from this study.
1. Participants diagnosed with diabetes
2. No recent eye surgery or eye procedure within 1 month
3. Participants who are unsuitable for Oculus K5M recording such as musculoskeletal
problems
4. Participants who are unable to tolerate Oculus K5M recording machine
5. Is pregnant, lactating or planning a pregnancy
6. Any other specified reason as determined by clinical investigator
4. STUDY DESIGN AND PROCEDURES/METHODOLOGY This is a randomised interventional trial with
Ocudox eyelid wipes and povidine iodine solution.
Study visits and duration:
Trial arms No. of study visits Study duration Ocudox eyelid wipes 3 21±3 days Povidine iodine
solution 3 21±3 days Recruitment duration: One year
Treatment arms and randomisation:
There will be 2 trial arms (parallel groups) in this study:
A. Ocudox eyelid wipes n=3 B. Povidine iodine solution n=3
Randomisation and Blinding
The randomisation procedure used will entail:
1. Presence of two witnesses
2. Drawing of lots
3. Randomization codes for the 2 groups will be noted. For e.g. 001A, 002B, etc.
4. Study information related to randomisation will be filed and kept at SERI
5. Only unblinded personnel have access to the randomization code file
There will be blinded and unblinded study team members in this study. Blinded study team
members will only be performing the procedures as described below. Unblinded study team
members will dispense the study product, counsel participants on directions for using Ocudox
eyelid wipes and also to clean the eyelid and conjunctiva if randomised to Povidone Iodine,
Directions for using Ocudox eyelid wipes:
Participant who received Ocudox eyelid wipes will be instructed to clean the eyelid according
to manufacturer's protocol during the study period (twice a day). A diary chart will be given
to all participants at the end of baseline visit. Participants will be asked to fill up the
diary chart whenever Ocudox eyelid wipes was used.
Directions for cleaning with Povidone Iodine:
• Pour 10ml of 10% Povidone Iodine into a 50ml Falcon tube.
- Dilute 10% of Povidone Iodine to 5% by pouring 10ml of saline and 10ml of Povidone
Iodine into a 50ml Falcon tube
- Prepare gauze and dip into the 10% Povidone Iodine solution
- Clean participant's exterior eye at least 2-3 times
- Next, flush the interior of the participant's eye with 5% Povidone Iodine
- Using a pasture pipette, flush the interior of the participant's eye
- Wait for 5 minutes
- After 5 minutes, rinse off with saline solution
- Thereafter, wait for 1 minute before adding tetracaine
- After adding tetracaine, wait for another minute before collection of microbiome swab.
Equipment used:
Oculus Keratograph 5M will be used on the baseline visit and post-treatment visits.
Workflow procedure:
Ocular symptoms will be examined subjectively using standard patient evaluation of eye
dryness (SPEED). Oculus Keratograph 5M will be conducted to assess tear meniscal height
(TMH), conjunctival redness and Non-invasive Tear Break-Up time (NIKBUT). Meibomain gland
evaluator will be used to assess the number of expressible glands. Bacteria on the eye
surface will be cultured from one of the conjunctivas (white part of the eyes) and Schirmers
I test will carry out to examine tear secretion and tear collection.
Outcomes:
Differences in Tear Meniscus Height, Ocular Redness, Non-invasive Tear Break-up time readings
and findings of DNA/RNA between study visits and study groups.
Figure 2. Study workflow
Details of study procedures shown below:
i) SPEED questionnaires Investigator will use the previously validated standard patient
evaluation of eye dryness (SPEED) questionnaire, which consists of 2 questions on frequency
and severity of dry eye graded on a scale of 0-3 on frequency, and grades 0-4 on severity.
Scores from all sub-questions will be added, and the greater the total score (0-28), the more
frequent or severe the dry eye (2).
ii) Non-invasive tear break-up time Both Oculus Keratograph 5M (Oculus, Wetzlar, Germany)
will be used to perform the non-invasive tear break up time (NIKBUT) (3). Briefly, seated
patients blink freely while fixing on a target ahead. Once ready, patients blink twice and
then refrain from further blinking. The fully automated instrument will capture any break or
distortion in the image of the projected rings on the cornea and the timings will be
automatically recorded. One reading will be taken per eye (4).
iii) Conjunctiva redness & Tear meniscus height Oculus Keratograph 5M (Oculus, Wetzlar,
Germany) will be used to measure conjunctival redness. After scanning the ocular surface and
images captured, grading of the conjunctival hyperemia (0-4) will be automatically performed
with subtraction of major conjunctival blood vessels, and temporal bulbar, nasal bulbar and
average readings will be obtained. Higher redness scores indicate more hyperemia(5). Height
of the tear meniscus can be measured by dragging the ruler option icon and the measured value
will appear in mm.
iv) Meibomain Gland Evaluator Meibomian glands will be assessed by gently squeezing the lower
eyelids using a device that delivers standardised pressure to the eyelids (Meibomian gland
expresser, TearScience, France). Texture of the expressed secretion will be graded as liquid
or viscous. The number of expressible glands will be recorded.
v) Collection of microbiome One specimens of microbiome will be collected from both eyes
First: a drop of non-preserved tetracaine will be instilled into the conjunctival fornix.
After the stinging sensation has resolved, a sterile cotton swap will be used to collect the
microbes from the lower conjunctival fornix using a gentle rolling action (up to 8 strokes).
The procedure is then repeated for the opposite eye.
These swaps will then be soaked in DNA/RNA Shield (Zymo) reagent and immediately homogenised
for 1 minute, stop at 30 seconds, and keep on ice for 1 minute, and homogenized for another
30 seconds. Homogenised samples will be stored at 4°C. This ensures an optimal and sufficient
DNA/RNA yield for our purpose. Subsequent nucleic acid extraction, PCR, sequencing, and
bioinformatics procedures will be performed by our collaborators. Storage: intended to be
analysed within a year, not more than 5 years.
Analysis: Investigator intend to compare composition of known microbes at the specie and
genus level after obtaining the reads in the non-human DNA metagenomics signatures.
vi) Schirmers I test Schirmer I test will be done with the standard 5 mm wide Test Strips
(Clement Clark) with a notch for folding, without prior anaesthesia. The strips will be
positioned over the inferior temporal half of the lower lid margin in both eyes, and
participants' eyes will then close. The extent of the wetting will be recorded after 5
minutes, and strips stored at -80˚C until further analysis(7).
