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Trial registered on ANZCTR


Registration number
ACTRN12617000096358
Ethics application status
Approved
Date submitted
22/11/2016
Date registered
17/01/2017
Date last updated
15/05/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Subthreshold micropulse yellow (577nm) laser versus half-dose photodynamic therapy for central serous chorioretinopathy : a randomized controlled pilot study
Scientific title
Subthreshold micropulse yellow (577nm) laser versus half-dose photodynamic therapy for central serous chorioretinopathy : a randomized controlled pilot study
Secondary ID [1] 290606 0
None
Universal Trial Number (UTN)
U1111-1190-2544
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Central serous chorioretinopathy 301093 0
Condition category
Condition code
Eye 300868 300868 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Half-dose Photodynamic therapy
The Photodynamic therapy (PDT)(intravenous infusion) will be performed using half-dose verteporfin (Visudyne; Novartis). For this, 3 mg/m2 of verteporfin will be infused over 10 minutes, and 15 minutes after beginning the infusion, the laser treatment will be begun. The total light energy delivered to the area of hyperpermeability is 50 J/cm2 over 83 seconds. The area of irradiation will be set to cover the hyperfluorescent area measured in the images recorded during the middle to late phases of indocyanine green angiography (ICGA).

If both eyes meet the inclusion criteria, only the right eye will be included in bilateral cases.

In photodynamic therapy, a light-sensitive medicine called verteporin (Visudyne)
is injected into the bloodstream. Laser light is then shone into the eye, which activates the medicine and the abnormal choroidal blood vessels is treated. In micropulse laser, a continuous-wave laser beam is chopped into a train of tiny, repetitive, low energy pulses, to treat the areas of diseased retinal pigment epithelium (RPE), inducing resorption of the subretinal fluid.

Patients in the PDT group will be considered for retreatment every 6 months whereas patients in the micropulse laser group will be considered for retreatment every 3 months. Patients who have persistent subretinal fluid after 3 treatments of micropulse laser will receive half-dose photodynamic therapy as rescue therapy, 3 months after the third micropulse laser treatment. In the PDT group, patient who have persistent subretinal fluid 6 months after the initital treatment will receive second half-dose photodynamic therapy.
Intervention code [1] 296469 0
Treatment: Devices
Comparator / control treatment
Subthreshold micropulse yellow laser

The focal leaking points and areas of hyperpermeability shown in pretreatment FA and ICGA will be used to guide the subthreshold micropulse laser therapy with 577nm yellow laser (IRIDEX IQ 577 laser, USA) delivered through the PDT laser lens (Volk Optical Inc, Mentor, OH, USA). Micropulse laser with spot size of 200 micro meter, 0.2 s exposure time, 400mW, a duty cycle of 5%, will be applied in 7x7 treatment grid pattern over areas of focal and diffuse RPE leak, using TxCellTM Scanning Laser Delivery System.

In the micropulse laser group, 30 ml normal saline will be infused instead of verteporfin, before application of micropulse laser. After treatment, you need to wear protective spectacles and avoid strong light for 2 days. You will need to attend clinic follow up visits at Hong Kong Eye Hospital or CUHK Eye Centre at 1, 3, 6, 9 and 12 months after the treatment. All investigations will be performed during your routine follow-up visits. No extra visits are necessary. Upon follow up, you will you will receive microperimtery and imaging with optical coherence tomography (OCT). Fluorescein angiography (FA) and indocyanine green angiography (ICGA) will be performed for patients with persistent subretinal fluid after the treatment, as decided by the doctors.
Control group
Active

Outcomes
Primary outcome [1] 300276 0
proportion of eyes with complete absorption of subretinal fluid (SRF) at 12 months

The absorption of subretinal fluid is assessed using an optical coherence tomography (OCT) scan
Timepoint [1] 300276 0
12 months
Secondary outcome [1] 329586 0
Serial changes in logMAR BCVA

Using a logMAR visual acuity chart
Timepoint [1] 329586 0
Using a logMAR visual acuity chart to see serial changes in logMAR BCVA in 1, 3, 6, 9 and 12 months.
Secondary outcome [2] 329760 0
Serial changes in central foveal thickness

Using optical coherence tomography (OCT) scan
Timepoint [2] 329760 0
Using optical coherence tomography (OCT) scan to see serial changes in central foveal thickness in 1, 3, 6, 9 and 12 months.
Secondary outcome [3] 329761 0
Serial changes in OCT morphological features

Using optical coherence tomography (OCT) scan
Timepoint [3] 329761 0
Using optical coherence tomography (OCT) scan to see serial changes in OCT morphological features in 1, 3, 6, 9 and 12 months.
Secondary outcome [4] 329762 0
Serial changes in microperimetry sensitivity

Using a microperimeter
Timepoint [4] 329762 0
Using a microperimeter to see serial changes in microperimetry sensitivity in 1, 3, 6, 9 and 12 months.
Secondary outcome [5] 329763 0
Serial changes in FA and ICGA

Serial fluorescein angiogram and indocyanine green angiogram
Timepoint [5] 329763 0
using serial fluorescein angiogram and indocyanine green angiogram to see serial changes in FA and ICGA in 1, 3, 6, 9 and 12 months.
Secondary outcome [6] 329764 0
The time needed for a complete resolution of the SRF after the primary treatment

Using optical coherence tomography (OCT) scan
Timepoint [6] 329764 0
Using optical coherence tomography (OCT) scan to see the time needed for a complete resolution of the SRF after the primary treatment in 1, 3, 6, 9 and 12 months.
Secondary outcome [7] 329765 0
The time to a recurrence of an SRF

Using optical coherence tomography (OCT) scan
Timepoint [7] 329765 0
Using optical coherence tomography (OCT) scan to see the time to a recurrence of an SRF in 1, 3, 6, 9 and 12 months.
Secondary outcome [8] 329766 0
Systemic and ocular complications during the study.

No additional tools or tests as this is a clinical finding
Timepoint [8] 329766 0
No additional tools or tests would be used for looking at systemic and ocular complications during the study in 1, 3, 6, 9 and 12 months

Eligibility
Key inclusion criteria
(1) CSCR is defined by idiopathic, single, or multiple serous detachments of the neurosensory retina in the macular area associated with RPE changes or RPE leaks on fluorescein angiography (FA) and visual symptoms for less than 3 months(acute CSCR) or more than 3 months (chronic CSCR)
(2) Patient with 18 years or older
(3) Absence of spontaneous resolution or improvement induced by empirical treatment such as acetazolamide or ketoconazole
(4) Presence of written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Any previous treatment, including PDT and focal thermal laser photocoagulation, for CSCR
(2) Iatrogenic CSC caused by corticosteroids
(3) FA or ICGA findings of CNV, polyploidal choroidal vasculopathy (PCV)
(4) Other maculopathy on clinical examination, FA, indocyanine green angiography (ICGA)
(5) Media opacity such as cataract that could interfere with adequate acquisition of OCT, FA and ICGA images

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 randomized into the half-dose PDT group or the subthreshold micropulse yellow (577-nm) laser group at a ratio of 1:1. The randomization sequence will be generated using a computerized randomization table kept centrally by a research assistant. All patients and investigators will be masked to the treatment allocation group. Assessors performing the follow-up assessments also will be masked to the patient allocation group. In the micropulse laser group, 30 ml normal saline will be infused instead of verteporfin, before application of micropulse laser. The infusion syringes will be wrapped externally with aluminum foil. After treatment, all patients will be given protective spectacles and will be instructed to avoid strong light for 3 days.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization sequence will be generated using a computerized randomization table kept centrally by a research assistant.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Statistical analysis was performed using SPSS software version 20.0 (SPSS, Inc., Chicago, IL). Analysis is performed as intention to treat. Comparisons of categorical variables between the 2 groups are performed using the chi-square test or the Fisher exact test, and continuous variables are compared using a 2-tailed t test or Mann–Whitney U test. A P value of equal/ not more than 0.05 is considered as statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/11/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
34
Final
Recruitment outside Australia
Country [1] 8409 0
Hong Kong
State/province [1] 8409 0

Funding & Sponsors
Funding source category [1] 295036 0
Government body
Name [1] 295036 0
Health and Medical Research Fund
Country [1] 295036 0
Hong Kong
Primary sponsor type
Individual
Name
Brelen Marten Erik
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] 293853 0
None
Name [1] 293853 0
Address [1] 293853 0
Country [1] 293853 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296393 0
Kowloon Central Kowloon East Cluster
Ethics committee address [1] 296393 0
Block S, Queen Elizabeth Hospital
30 Gascoigne Road
KOWLOON
Ethics committee country [1] 296393 0
Hong Kong
Date submitted for ethics approval [1] 296393 0
05/11/2015
Approval date [1] 296393 0
12/01/2016
Ethics approval number [1] 296393 0
KC/KE-15-0192/FR-3
Ethics committee name [2] 296394 0
The Joint Chinese University of Hong Kong – New Territories East Cluster Clinical Research Ethics Committee
Ethics committee address [2] 296394 0
8/F, Lui Che Woo Clinical Sciences Building,
Prince of Wales Hospital, Shatin, Hong Kong
Ethics committee country [2] 296394 0
Hong Kong
Date submitted for ethics approval [2] 296394 0
15/10/2015
Approval date [2] 296394 0
22/12/2015
Ethics approval number [2] 296394 0
CRE-2015.573

Summary
Brief summary
Purpose
This randomized controlled pilot clinical trial aims to compare the efficacy and safety of half-dose photodynamic therapy(PDT) and subthreshold micropulse yellow (577-nm) laser in central serous chorioretinopathy (CSCR).

Methods
This will be a prospective, double-masked, randomized controlled study. Patients with CSCR attending at Hong Kong Eye Hospital between January 2016 and December 2016 will be recruited in the study. If both eyes meet the inclusion criteria, only the right eye will be included in bilateral cases. Patients will be randomized into the half-dose PDT group or the subthreshold micropulse yellow (577-nm) laser group at a ratio of 1:1.

All patients and investigators will be masked to the treatment allocation group. Assessors performing the follow-up assessments also will be masked to the patient allocation group.

Half-dose Photodynamic therapy
The PDT will be performed using half-dose verteporfin (Visudyne; Novartis AG). For this, 3 mg/m2 of verteporfin will be infused over 10 minutes, and 15 minutes after beginning the infusion, the laser treatment will be begun. The total light energy delivered to the area of hyperpermeability is 50 J/cm2 over 83 seconds.

Subthreshold micropulse yellow laser
The focal leaking points and areas of hyperpermeability will be treated with the subthreshold micropulse laser therapy with 577nm yellow laser (IRIDEX IQ 577 laser, USA). In the micropulse laser group, 30 ml normal saline will be infused instead of verteporfin, before application of micropulse laser.

Baseline and follow-up examinations
Patients will be assessed at baseline and followed up at 1, 3, 6, 9 and 12 months after the treatment. At the baseline and all post-treatment visits, best-corrected visual acuity (BCVA), will be measured. The optical coherence topography (OCT) (Topcon DRI OCT, Triton OCT, Japan; Spectralis OCT, Heidelberg Engineering Inc., Heidelberg, Germany) and microperimtery will be performed before the treatment as well as at each clinical visit. Patients with persistent subretinal fluid will have further fluorescein angiography (FA) and indocyanine green angiography (ICGA) as decided by the assessors.

Retreatment will be considered if the patients meet two of the three following criteria: decreased visual acuity of at least one line from baseline, presence of subretinal fluid on OCT, and significant leakage on angiography. Patients in the PDT group will be considered for retreatment every 6 months whereas patients in the micropulse laser group will be considered for retreatment every 3 months. Patients who have persistent SRF after 3 treatments of micropulse laser will receive half-dose photodynamic therapy as rescue therapy, 3 months after the third micropulse laser treatment.

The primary outcome of the study is the proportion of eyes with complete absorption of subretinal fluid (SRF) at 12 months. Secondary outcome measures included serial changes in logMAR BCVA, central foveal th
Trial website
None
Trial related presentations / publications
None
Public notes
None
Attachments [1] 1258 1258 0 0
/AnzctrAttachments/371369-530-KCKE & NTEC Approval.pdf (Ethics approval)
Attachments [2] 1259 1259 0 0
/AnzctrAttachments/371369-KCKE-Protocol - micropulse vs half dose PDT in chronic CSCR_20151124.pdf (Protocol)
Attachments [3] 1260 1260 0 0
/AnzctrAttachments/371369-KCKE-Consent Info_English_KCC 20151124_clean.pdf (Participant information/consent)
Attachments [4] 1261 1261 0 0
/AnzctrAttachments/371369-KCKE-3.1 Informed Consent Form (Chi) - 20151218_clean.pdf (Participant information/consent)
Attachments [5] 1262 1262 0 0
/AnzctrAttachments/371369-NTEC-Consent Info_Chinese_PWH 20151203_clean.pdf (Participant information/consent)
Attachments [6] 1263 1263 0 0
/AnzctrAttachments/371369-NTEC-Consent Info_English_PWH 20151203_clean.pdf (Participant information/consent)
Attachments [7] 1264 1264 0 0
/AnzctrAttachments/371369-NTEC-Protocol - micropulse vs half dose PDT in CSCR_20151203.pdf (Protocol)

Contacts
Principal investigator
Name 68534 0
Prof Brelen Marten Erik
Address 68534 0
Department of Ophthalmology & Visual Sciences,
3/F, Hong Kong Eye Hospital
147K Argyle Street
KOWLOON
Country 68534 0
Hong Kong
Phone 68534 0
+852-39435825
Fax 68534 0
Email 68534 0
[email protected]
Contact person for public queries
Name 68535 0
Miss Janice Wong
Address 68535 0
Department of Ophthalmology & Visual Sciences,
3/F, Hong Kong Eye Hospital
147K Argyle Street
KOWLOON
Country 68535 0
Hong Kong
Phone 68535 0
+852-39435825
Fax 68535 0
Email 68535 0
[email protected]
Contact person for scientific queries
Name 68536 0
Prof Brelen Marten Erik
Address 68536 0
Department of Ophthalmology & Visual Sciences,
3/F, Hong Kong Eye Hospital
147K Argyle Street
KOWLOON
Country 68536 0
Hong Kong
Phone 68536 0
+852-39435825
Fax 68536 0
Email 68536 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23453Study protocol    371369-(Uploaded-22-02-2023-13-16-28)-Study-related document.docx
23454Informed consent form    371369-(Uploaded-22-02-2023-13-16-28)-Study-related document.doc
23455Ethical approval    371369-(Uploaded-22-02-2023-13-27-33)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.