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Trial registered on ANZCTR


Registration number
ACTRN12618000826246
Ethics application status
Approved
Date submitted
4/08/2017
Date registered
15/05/2018
Date last updated
25/06/2019
Date data sharing statement initially provided
21/06/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A biomarker for fast progressors in glaucoma?
Scientific title
Progressive lamina cribrosa deformation – A biomarker for fast progressors in glaucoma?
Secondary ID [1] 292599 0
None
Universal Trial Number (UTN)
U1111-1200-3392
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glaucoma 304279 0
Condition category
Condition code
Eye 303625 303625 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Continued treatment group:
Participants will continue to receive the same treatment started before recruitment. Participants reaching any of the end-points, including VF progression, decrease in VA greater than or equal to 2 lines, and IOP greater than 30mmHg on 2 consecutive follow-up visits in anytime during the study period will be excluded from the study and receive additional treatment, which is the same as the additional IOP lowering treatment group.

Only the investigator (ophthalmologist)will deliver the intervention.
Intervention code [1] 298811 0
Treatment: Drugs
Comparator / control treatment
Additional IOP lowering treatment group:
Participants will receive additional treatment after randomization to decrease the baseline IOP in the following order: prostaglandin analogue (PGA, once daily)(route of administration: intraocular, duration for 4-month, type: eye drop) (Such as Travatan Z (0.004%) and Xalatan 2.5 ml may be used depending on the discretion of the attending doctor) , Brimonidine tartrate 0.2% (2 mg/mL) eyedrops (route of administration: intraocular, duration for 4-month, three time daily), carbonic anhydrase inhibitor (CAI, three times oral daily for 4-month, 250 to 1000 mg (usage depending on the discretion of the attending doctor). Treatment is cumulative, i.e. participants receive PGA, then PGA AND Brimonidine tartrate, then PGA AND Brimonidine tartrate and CAI. For patients who are already on maximum tolerated medications, SLT will be performed with treatment protocol as described previously (360° for 100 applications) and participant will receive one more additional follow-up visit.

Selective Laser Trabeculoplasty (SLT) has a treatment spot size of 400µm and the energy of each treatment pulse (3 ns) typically varies between 0.6mJ and 1.2mJ. In other words, the energy applied per mm2 ranges from 4.8 to 9.5 mJ.

SLT is performed with Selecta II SLT (Lumenis). A drop of 0.1% brimonidine is instilled into the eye 15 minutes prior to treatment. After instilling a drop of 0.5% proparacaine 0.5%, the Latina lens with coupling fluid is then attached to the cornea and the TM is visualized. The laser spot size is 400 µm and the treatment duration is 3 ns. The energy is increased by 0.1 mJ from 0.6 mJ until champagne-like bubbles are formed on the inferior TM. The energy is then reduced by 0.1 mJ for the rest of treatment. The contact lens is rotated until the TM is treated for 360° with no overlap and no gap of the treatment spots. Topical non-steroidal anti-inflammatory drug (Ketorolac) is applied for 5 days following the treatment.

IOP lowering treatment will be given to eyes randomized to the additional treatment arm in the following order: prostaglandin analogue (PGA), brimonidine, carbonic anhydrase inhibitor (CAI). For example, if the current treatment is a PGA, the additional treatment will be brimonidine. It has been shown in eyes receiving PGA, the average additional IOP reduction was 20% for brimonidine for 4 months, and 13% to 16% for CAI for another 4 months. For patients who are already on maximum tolerated medications, SLT will be performed with treatment protocol as described previously (360° for 100 applications).
Control group
Active

Outcomes
Primary outcome [1] 302980 0
Use of two Visual Field tests, separated by at least 30 min., will be performed for each eye at the baseline visit.

Outcome would be "Proportion of eyes with VF progression ".
Timepoint [1] 302980 0
every 4-month in 2 years post randomisation.
Secondary outcome [1] 337613 0
Proportion of eyes with RNFL progression

Use of SDOCT imaging to assess
Timepoint [1] 337613 0
every 4-month in 2 years post randomisation.
Secondary outcome [2] 337614 0
Rate of change visual field index

Use of visual field tests to assess
Timepoint [2] 337614 0
every 4-month in 2 years post randomisation.
Secondary outcome [3] 337615 0
Rate of change of LC deformation before and after IOP reduction

Use of visual fields results and. SDOCT imaging and corneal hysteresis (Ocular Response Analyzer), and other biometric and ocular variables (e.g. axial length and ocular perfusion pressure)
Timepoint [3] 337615 0
every 4-month in 2 years post randomisation.

Eligibility
Key inclusion criteria
1.Age 18 years or older
2.Best corrected visual acuity greater than or equal to 20/40
3.POAG patients diagnosed within 12 months without prior history of glaucoma surgical/laser procedure and receiving not more than one topical IOP lowering medication and have been followed up at least 36 months in ongoing study named as “Diagnostic Imaging Assessment in the Evaluation of Glaucomatous Optic Neuropathy and diagnosed with glaucoma “at Hong Kong Eye Hospital'.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
IOP >30mmHg measured at any time points during the screening visit; high myopia (spherical error<-6.0D); moderate and advanced VF loss (VF MD <-6dB in the worse eye) or defects close to fixation (any one of the paracentral points with sensitivity <10dB); inability to perform reliable VF; suboptimal quality of SDOCT images (see SDOCT imaging); previous intraocular surgery other than uncomplicated cataract extraction; and diabetic retinopathy/maculopathy.

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)
Phase I (36 Months):
168 consecutive patients with primary open-angle glaucoma (POAG) (patients who have been followed up at least 36 months in ongoing study named as “Diagnostic Imaging Assessment in the Evaluation of Glaucomatous Optic Neuropathy and diagnosed with glaucoma “at Hong Kong Eye Hospital) will be recruited. Eyes with progressive LC deformation detected by SDOCT will be randomized to receive additional IOP lowering treatment or continue the current treatment. For patients without progressive LC deformation, they will be randomized with the same manner. Participants no need to receive extra investigations in Phrase I under this study. As participants have completed examinations under “Diagnostic Imaging Assessment in the Evaluation of Glaucomatous Optic Neuropathy and diagnosed with glaucoma “ at least 36 months. Recruited participants will enter Phrase II under this study directly.

Phase II (24 months):
After subjects have been followed up at least 36 months under “Diagnostic Imaging Assessment in the Evaluation of Glaucomatous Optic Neuropathy and diagnosed with glaucoma “, participants with LC deformation will be randomized at a ratio of 1:1 to either additional IOP lowering treatment group or continued treatment group. Participants without progressive LC deformation will also be randomized at a ratio of 1:1 in the same manner. After randomization, participants will be followed with SDOCT imaging and perimetry 4-monthly within 24 months.

All participants will undergo the following examinations 4-monthly at Phrase II, including:
1. VA measurement
2. Slit-lamp biomicroscopy for the anterior and posterior segments
3. GAT IOP
4. Blood pressure measurements
5. Dark room indentation gonioscopy with Posner lens
6. Axial length measurement with A-scan biometry
7. Central corneal thickness with ultrasound pachymetry
8. Refraction with Auto-refractor
9. Corneal hysteresis
10. Perimetry
a. Two Visual Field tests, separated by at least 30 min., will be performed for each eye at the baseline visit.
11. SDOCT imaging

All participants will under dilated fundus examination with color optic disc stereophotography yearly.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
12 follow-up visits over 36 months would be available for detection of progressive LC deformation at the end of Phase I. Progressive posterior LC deformation will be determined by trend analysis of meridional ALCSD. Progressive posterior LC deformation is confirmed when greater than or equal than 1 meridional ALCSD from any one of the six meridians (the optic nerve head is longitudinally imaged using 6 equally-spaced radial B-scans by the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) with image registration) demonstrates a significant negative trend (i.e. rate of change of ALCSD less than 0µm/year with p less than 0.05) for the 2 most recent visits by the end of Phase I. ALCSD will be measured with reference to the choroid sclera interface (CSI). In a recent study, we showed that ALCSD measured with reference to the CSI is less susceptible to the influence of age-related or disease-related choroidal thinning in glaucoma patients.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
168
Accrual to date
6
Final
Recruitment outside Australia
Country [1] 9129 0
Hong Kong
State/province [1] 9129 0

Funding & Sponsors
Funding source category [1] 297188 0
Government body
Name [1] 297188 0
University Grants Committee- General Research Fund
Country [1] 297188 0
Hong Kong
Primary sponsor type
Individual
Name
Prof Leung Kai Shun Christopher
Address
Department of Ophthalmology & Visual Sciences
The Chinese University of Hong Kong
4/F Hong Kong Eye Hospital
147K Argyle Street, Mongkok,
Hong Kong SAR
Country
Hong Kong
Secondary sponsor category [1] 296195 0
None
Name [1] 296195 0
Address [1] 296195 0
Country [1] 296195 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298345 0
Research Ethics Committee (Kowloon Central / Kowloon East)
Ethics committee address [1] 298345 0
Room 414, Nurse Quarters, Queen Elizabeth Hospital
30 Gascoigne Road, Kowloon, Hong Kong
Ethics committee country [1] 298345 0
Hong Kong
Date submitted for ethics approval [1] 298345 0
03/10/2014
Approval date [1] 298345 0
20/11/2014
Ethics approval number [1] 298345 0
KC/KE-14-0198/FR-2
Ethics committee name [2] 303654 0
Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee
Ethics committee address [2] 303654 0
8/F, Lui Che Woo Clinical Sciences Building,
Prince of Wales Hospital, Shatin
Ethics committee country [2] 303654 0
Hong Kong
Date submitted for ethics approval [2] 303654 0
15/10/2014
Approval date [2] 303654 0
10/11/2014
Ethics approval number [2] 303654 0
2014.532
Ethics committee name [3] 303655 0
Kowloon West Cluster Research Ethics Committee (KWC-REC)
Ethics committee address [3] 303655 0
Room 533, 5/F, Block J, Princess Margaret Hospital, NT
Ethics committee country [3] 303655 0
Hong Kong
Date submitted for ethics approval [3] 303655 0
03/11/2014
Approval date [3] 303655 0
19/01/2015
Ethics approval number [3] 303655 0
KW/EX-14-216(82-23)

Summary
Brief summary
The study is complied with ICH-GCP. This is a 2-year prospective, multicenter, randomized treatment trial with a primary objective to test whether glaucomatous eyes (receiving not more than one topical IOP lowering medication at the time of recruitment) with observable progressive
LC deformation randomized to additional treatment (IOP reduction) have a greater absolute risk reduction (ARR) of VF (primary outcome measure) and RNFL (secondary outcome measure) progression (i.e. the difference in the proportion of eyes with VF/RNFL progression between the additional treatment and continued treatment groups) compared with those without progressive
LC deformation randomized to the same manner. In other words, we expect ARR (LC
deformation) > ARR (no LC deformation). Eyes without progressive LC deformation are also randomized because they may also demonstrate further VF progression independent of LC deformation and respond to IOP lowering treatment. The comparison between ARR (LC deformation) and ARR (no LC deformation) will afford an objective measure to quantify the relative treatment effect on eyes with detectable LC deformation.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1946 1946 0 0
/AnzctrAttachments/373431-KCKE Research Protocol_20170519_clean.pdf (Protocol)
Attachments [2] 1947 1947 0 0
/AnzctrAttachments/373431-Informed Consent Form (English)_clean_ 170505(2).pdf (Participant information/consent)
Attachments [3] 1948 1948 0 0
/AnzctrAttachments/373431-Informed Consent Form (Chinese)_clean_20170505(2).pdf (Participant information/consent)
Attachments [4] 1949 1949 0 0
/AnzctrAttachments/373431-484-KCKE Approvals.pdf (Ethics approval)

Contacts
Principal investigator
Name 76782 0
Prof Leung Kai Shun Christopher
Address 76782 0
Department of Ophthalmology & Visual Sciences,
3/F, Hong Kong Eye Hospital
147K Argyle Street
KOWLOON
Country 76782 0
Hong Kong
Phone 76782 0
+85239435818
Fax 76782 0
Email 76782 0
cksleung@cuhk.edu.hk
Contact person for public queries
Name 76783 0
Miss Ms Jennifer Tsoi
Address 76783 0
Department of Ophthalmology & Visual Sciences,
3/F, Hong Kong Eye Hospital
147K Argyle Street
KOWLOON
Country 76783 0
Hong Kong
Phone 76783 0
+85239435818
Fax 76783 0
Email 76783 0
jennifertsoi@cuhk.edu.hk
Contact person for scientific queries
Name 76784 0
Prof Leung Kai Shun Christopher
Address 76784 0
Department of Ophthalmology & Visual Sciences,
3/F, Hong Kong Eye Hospital
147K Argyle Street
KOWLOON
Country 76784 0
Hong Kong
Phone 76784 0
+85239435818
Fax 76784 0
Email 76784 0
cksleung@cuhk.edu.hk

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be available due to privacy concerns.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2412Study protocol    373431-(Uploaded-21-06-2019-13-39-08)-Study-related document.docx
2413Informed consent form    373431-(Uploaded-21-06-2019-13-39-35)-Study-related document.doc
2414Ethical approval    373431-(Uploaded-21-06-2019-13-51-03)-Study-related document.pdf



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.