Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000704897
Ethics application status
Approved
Date submitted
19/06/2012
Date registered
2/07/2012
Date last updated
9/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Laser Intervention in Early Age-Related Macular Degeneration (LEAD) Study
Scientific title
A multi-centre, randomised trial into the safety and efficacy of nanosecond microsurgical laser intervention in early age-related macular degeneration.
Secondary ID [1] 280698 0
CERA201201
Universal Trial Number (UTN)
U1111-1131-9425
Trial acronym
LEAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Age related Macular Degeneration 286736 0
Condition category
Condition code
Eye 287035 287035 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Ellex 2RT (TM) laser system is a surgical laser instrument designed for use by ophthalmologists for performing retinal procedures in order to treat conditions such as AMD.
The instrument is capable of producing a treatment beam having a short pulse of focused laser light with a wavelength of 532nm (green). These pulses can be accurately positioned on the retina of a patient's eye with the aid of a slitlamp microscope and a 635nm (red) aiming beam system. The aiming and treatment spot sizes are fixed at 400 microns at the system focal plane.
The coaxial aiming beam is used to position the treatment beam onto the target tissue, and a 1:1 contact lens is used for retinal treatment. The energy contained within the single short pulse is focused to the required spot size at the treatment plane so that pigmented cells can be selectively destroyed without rupturing the cell walls and without causing collateral damage to neighbouring cells or structures. The wound healing response that is then triggered is intended to improve function.

The 2RT laser will be used to deliver 12 laser shots in two arcs of 6 shots superiorly and 6 shots inferiorly, inside the retinal vascular arcades at an approximate distance from the fovea of 3000 microns, with approximately one laser spot diameter between them. Laser treatment takes no more than 10 minutes but may be repeated each 6 months.
The energy settings used for each of the 12 treatment single pulse laser shots will be between 0.12 mJ and 0.40 mJ, i.e., one step below the threshold energy level used to achieve blanching (or if no blanching achieved, an energy setting of 0.4mJ). Laser re-treatments may be performed at 6 monthly intervals for those participants continuing to meet none of the exclusion criteria.
Intervention code [1] 285116 0
Treatment: Devices
Comparator / control treatment
The sham laser procedure will be implemented to mimic active laser treatment.
The patient will be positioned at the chinrest of the 2RT laser in the normal manner and the contact lens used to observe the macula via the slit-lamp microscope, using minimum illumination. To simulate laser application the maximum illumination button will be briefly pressed by the operating physician at each of the 12 locations described above where and when the laser would normally be applied. The laser remains in standby mode preventing accidental laser firing.
Control group
Placebo

Outcomes
Primary outcome [1] 287370 0
Progression to advanced age related macular degeneration (AMD) in the treated eye as assessed by clinical ocular examination, colour fundus photography, Ocular Coherence Tomography, and Fluorescein Angiography as required.
Timepoint [1] 287370 0
36 months post initial laser treatment
Secondary outcome [1] 298014 0
Progression to advanced AMD non-treated eye as assessed by clinical ocular examination, colour fundus photography, Ocular Coherence Tomography, and Fluorescein Angiography as required.
Timepoint [1] 298014 0
36 months post initial sham laser procedure

Eligibility
Key inclusion criteria
Age 50 years and older, and less than 95 years. Best Corrected Visual Acuity (BCVA) of 6/12 (20/40) or better in each eye. Bilateral high-risk early AMD (AREDS Simplified Severity Scale, at least 2 risk factors) within an inner macular zone (a circle with a radius of 1500 microns centered on the fovea). A threshold sensitivity less than 25 dB at any point, within a customised grid, as measured using a Macular Integrity Assessment (MAIA) device, at the same location of the one eye on two separate occasions. Pupil dilation of 5mm or more in each eye. Fundus photographs, OCT and FAF images of adequate quality as assessed by the LEAD Image Reading Centre. Ability and willingness to consent, and be randomised, to 2RT or sham laser treatment, and all qualification and follow-up phases of the study.
Minimum age
50 Years
Maximum age
95 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any imaged retinal sign suggestive of geographic atrophy within the macula (a circle with a radius of 3000 microns centred on the fovea). Peri-papillary atrophy further than 1500 microns from the fovea is allowed.
CNV, or past treatment for CNV, in either eye.
Any other experimental treatment for AMD, excluding dietary supplements, received in the past 12 months or thought likely to chronically change the course of the participant’s retinal disease.
Any OCT image showing evidence of intraretinal fluid (cysts), or subretinal fluid for which CNV cannot be excluded as a cause.
A subfoveal pigment epithelial detachment/drusenoid detachment greater than 1000 microns in diameter in either eye.
Ocular disease in either eye, other than AMD, which may significantly compromise assessment of the retina, including;
Known hypersensitivity to fluorescein.
Previous retinal or ocular surgery, the effects of which may now or in the future complicate assessment of the progression of AMD.
Requirement for any systemic or ocular medication known to be toxic to the retina.
Sensitivity to the application of a contact lens.
Any history of prior laser surgery to the retina.
IOP of 26 mm Hg or higher, or if there is some reason to believe that the participant may have glaucoma, (e.g., history of the diagnosis of glaucoma, medical, surgical or laser intervention for the treatment of glaucoma, or disc/nerve fibre layer defects suggestive of glaucoma).
Significant cataract: Nuclear cataract Grade 2 or 3, cortical cataract Grade 2 or 3 or posterior subcapsular cataract Grade 2 or 3, by Simplified Cataract Grading System (WHO Cataract Grading Group).

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving 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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/07/2012
Actual
30/07/2012
Date of last participant enrolment
Anticipated
Actual
15/04/2015
Date of last data collection
Anticipated
30/04/2018
Actual
1/05/2018
Sample size
Target
360
Accrual to date
Final
292
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA,VIC
Recruitment hospital [1] 2764 0
The Royal Victorian Eye and Ear Hospital - East Melbourne
Recruitment postcode(s) [1] 8462 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 6242 0
United Kingdom
State/province [1] 6242 0
Northern Ireland

Funding & Sponsors
Funding source category [1] 285468 0
Government body
Name [1] 285468 0
NHMRC
Country [1] 285468 0
Australia
Primary sponsor type
Other
Name
Centre for Eye Research Australia
Address
Level 1, Royal Victorian Eye and Ear Hospital
32 Gisborne Street
East Melbourne VIC 3002
Country
Australia
Secondary sponsor category [1] 284321 0
None
Name [1] 284321 0
Address [1] 284321 0
Country [1] 284321 0
Other collaborator category [1] 276866 0
Commercial sector/Industry
Name [1] 276866 0
Ellex R&D Pty Ltd
Address [1] 276866 0
82 Gilbert Street
Adelaide SA 5000
Country [1] 276866 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287480 0
RVEEH HREC
Ethics committee address [1] 287480 0
32 Gisborne Street
East Melbourne VIC 3002
Ethics committee country [1] 287480 0
Australia
Date submitted for ethics approval [1] 287480 0
Approval date [1] 287480 0
28/11/2011
Ethics approval number [1] 287480 0
11/1027H

Summary
Brief summary
The LEAD study is a multi-centre, double-blind, randomised, sham-procedure controlled, clinical trial designed to investigate the safety and efficacy of nanosecond laser microsurgical intervention as a treatment for early age-related macular degeneration. In addition, the study will provide information on visual function measures as a predictor for development of, and progression to advanced, AMD.
Trial website
Trial related presentations / publications
Lek, J. J., Brassington, K. H., Luu, C. D., Chen, F. K., Arnold, J. J., Heriot, W. J., & Guymer, R. H. (2017). Subthreshold Nanosecond Laser Intervention in Intermediate Age-Related Macular Degeneration: Study Design and Baseline Characteristics of the Laser in Early Stages of Age-Related Macular Degeneration Study (Report Number 1). Ophthalmology Retina. Ophthalmology Retina (2017)
Public notes

Contacts
Principal investigator
Name 34334 0
Prof Robyn Guymer
Address 34334 0
Centre for Eye Research Australia Level 1, 32 Gisborne Street East Melbourne VIC 3002
Country 34334 0
Australia
Phone 34334 0
+61 03 9929 8393
Fax 34334 0
Email 34334 0
[email protected]
Contact person for public queries
Name 17581 0
Ms Kate Brassington
Address 17581 0
Centre for Eye Research Australia Level 7, Royal Victorian Eye and Ear Hospital 32 Gisborne Street East Melbourne, VICTORIA 3002
Country 17581 0
Australia
Phone 17581 0
+61 3 99298362
Fax 17581 0
Email 17581 0
[email protected]
Contact person for scientific queries
Name 8509 0
Ms Kate Brassington
Address 8509 0
Centre for Eye Research Australia Level 7, Royal Victorian Eye and Ear Hospital 32 Gisborne Street East Melbourne, VICTORIA 3002
Country 8509 0
Australia
Phone 8509 0
+61 3 9929 8362
Fax 8509 0
Email 8509 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseSubthreshold Nanosecond Laser Intervention in Intermediate Age-Related Macular Degeneration: Study Design and Baseline Characteristics of the Laser in Early Stages of Age-Related Macular Degeneration Study (Report Number 1).2017https://dx.doi.org/10.1016/j.oret.2016.12.001
EmbaseDose response in the subthreshold nanosecond laser trial in early stages of AMD: A LEAD study report.2021https://dx.doi.org/10.3928/23258160-20210628-04
EmbaseSubthreshold Nanosecond Laser in Age-Related Macular Degeneration: Observational Extension Study of the LEAD Clinical Trial.2021https://dx.doi.org/10.1016/j.oret.2021.02.015
EmbaseSubthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration: The LEAD Randomized Controlled Clinical Trial.2019https://dx.doi.org/10.1016/j.ophtha.2018.09.015
EmbaseSecondary and Exploratory Outcomes of the Subthreshold Nanosecond Laser Intervention Randomized Trial in Age-Related Macular Degeneration: A LEAD Study Report.2019https://dx.doi.org/10.1016/j.oret.2019.07.008
EmbaseMulti-focal electro-retinogram response following sub-threshold nano-second laser intervention in age-related macular degeneration.2020https://dx.doi.org/10.1111/ceo.13823
EmbaseAssociation between Patient-Reported Outcomes and Time to Late Age-Related Macular Degeneration in the Laser Intervention in Early Stages of Age-Related Macular Degeneration Study.2020https://dx.doi.org/10.1016/j.oret.2020.03.015
Dimensions AISubthreshold Nano-Second Laser Treatment and Age-Related Macular Degeneration2021https://doi.org/10.3390/jcm10030484
N.B. These documents automatically identified may not have been verified by the study sponsor.