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Trial registered on ANZCTR


Registration number
ACTRN12622001246774p
Ethics application status
Submitted, not yet approved
Date submitted
7/09/2022
Date registered
15/09/2022
Date last updated
15/09/2022
Date data sharing statement initially provided
15/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Rapid Avastin (Bevacizumab) treatment and extension in low-risk age-related macular degeneration patients.
Scientific title
Palmerston North Interventional Rapid Avastin Treat & Extend (PIRATE) study in low-risk age-related macular degeneration patients.
Secondary ID [1] 307941 0
Nil
Universal Trial Number (UTN)
Trial acronym
PIRATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
age-related macular degeneration 327590 0
Condition category
Condition code
Eye 324679 324679 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In the PIRATE study we propose to investigate a modified treat and extend protocol. We will investigate extending treatment intervals by 4-weeks (treatment group) compared to the standard protocol of 2-weeks (control group).

Study population: Individuals with low-risk neovascular age-related macular generation (nAMD) (please see study protocol attached for specific low/high-risk stratification of nAMD).

Therapeutics: All participants will receive 0.05mL Bevacizumab (Avastin) 3.75mg/0.15mL administered as an intravitreal injection into the vitreous cavity of effected eye. These will be administered either by a qualified nurse injector or ophthalmology registrar/consultant.

Treatment frequency (treatment group): 3x Avastin at monthly intervals (induction), then treatment extension by 4 weeks if extension criteria meet (e.g. 8 weeks, 12 weeks, 16 weeks) until 16 weeks post-induction is reached (maximum treatment interval). If shortening criteria meet, then shortened by 4 weeks with each subsequent extensions will be at 2 weeks (as per standard protocol).

Treatment monitoring: each injection will be provided around a clinic appointment with optical coherence tomography (OCT) + clinical assessment. This will allow monitoring of treatment response or related adverse-effect. Strict shortening/extension/maintenance criteria has been established (please see study protocol attached for outlined criteria).

The term “rapid” corresponds to the treatment group’s 4-week treatment extension. Participants in this group will reach the 16 weeks maximal treatment interval in a minimum of 6 injections. The standard protocol (control group) in comparison takes a minimum of 9 injections. The treatment group has therefore a more “rapid” treatment extension as it requires fewer injections and therefore reaches the 16 weeks maximal extension "faster".
Intervention code [1] 324396 0
Treatment: Drugs
Comparator / control treatment
In the PIRATE study we propose to investigate a modified treat and extend protocol. We will investigate extending treatment intervals by 4-weeks (treatment group) compared to the standard protocol of 2-weeks (control group).

Study population: Individuals with low-risk neovascular age-related macular generation (nAMD) (please see study protocol attached for specific low/high-risk stratification of nAMD).

Therapeutics: All participants will receive 0.05mL Bevacizumab (Avastin) 3.75mg/0.15mL administered as an intravitreal injection into the vitreous cavity of effected eye. These will be administered either by a qualified nurse injector or ophthalmology registrar/consultant.

Treatment frequency (control group): 3x Avastin at monthly intervals (induction), then treatment extension by 2 weeks if extension criteria meet (e.g. 6 weeks, 8 weeks, 10 weeks, 12 weeks, etc.) until 16 weeks post-induction (maximal treatment interval) is reached. Shortening and maintenance as per current protocol.

Treatment monitoring: each injection will be provided around a clinic appointment with optical coherence tomography (OCT) + clinical assessment. This will allow monitoring of treatment response or related adverse-effect. Strict shortening/extension/maintenance criteria has been established (please see study protocol attached for outlined criteria).
Control group
Active

Outcomes
Primary outcome [1] 332498 0
Best corrected visual acuity using Early Treatment Diabetic Retinopathy Study (ETDRS) eye-chart equivalent.
Timepoint [1] 332498 0
12 months post-intervention commencement
Secondary outcome [1] 413740 0
Central macular thickness as defined by Zeiss Cirrus optical coherence tomography
Timepoint [1] 413740 0
12 months post-intervention commencement
Secondary outcome [2] 413741 0
Number of adverse injection-related events
(e.g. raised intraocular pressure, intraocular haemorrhage, retinal detachment, cataract formation, capsular tear, endophthalmitis). These will be determined by ophthalmology registrars/consultants involved in the study
Timepoint [2] 413741 0
12 months post-intervention commencement
Secondary outcome [3] 413742 0
Total number of injections
These will be determined by study investigators. A record will be kept of each injection on a secure data capture platform (REDCap). Total injection numbers will be assessed from the recorded data.
Timepoint [3] 413742 0
12 months post-intervention commencement
Secondary outcome [4] 413849 0
Whether treatment interval had to be shortened
Treatment interval would be shortened if any one of the following are met:
o New or persistent fluid with unchanged or increased fluid on OCT
o Loss of >5 EDTRs letters visual acuity
o Increase in CRT of >100 microns (in central 1mm region) compared to the lowest value measured on OCT
o New neovascularisation as determined by investigator
o New macular Haemorrhage

Please note that treatment interval decisions will be made by designated investigators by means of clinical review subsequent to treatments. This will be recorded in the secure research database; REDCAP.
Timepoint [4] 413849 0
12 months post-intervention commencement
Secondary outcome [5] 413850 0
Number of large macular haemorrhages
As determined by investigator during dilated fundoscopic examination or using fundus photography
Timepoint [5] 413850 0
12 months post-intervention commencement
Secondary outcome [6] 413851 0
Total number of appointments of age-related macular degeneration appointments
These will be determined by study investigators. A record will be kept of each injection on a secure data capture platform (REDCap). Total injection numbers will be assessed from the recorded data.
Timepoint [6] 413851 0
12 months post-intervention commencement

Eligibility
Key inclusion criteria
•Patients greater than or equal to 50 years of age
•Low-risk nvAMD characteristics (see risk-stratification outlined below) with likely subfoveal or juxtafoveal choroidal neovascular membrane (CNVM). These being diagnosed clinically, confirmed by investigator (ophthalmology registrar or ophthalmologist)
•Deemed appropriate for Avastin therapy by investigator
•Best corrected visual acuity (BCVA) between 6/12 - 6/180 at first visit in study eye
•If both eyes affected then the eye with the worse BCVA will be included in the trial as the study eye
•Participants must be willing and able to provide independent informed consent

Participants with be stratified based on their nAMD characteristics. High-risk participants will be deemed anyone who meets one or more of the following criteria:
1. Monocular patients (i.e. only have a single good-seeing eye)
2. Macular haemorrhage (greater or equal to 1 disc diameter) clinically or on fundus photo
3. History of previous of large macular haemorrhage
4. Subretinal fluids (SRF) less than 200 microns
5. Recent reduction of injection frequency for any reason (i.e. if shortened by 4 weeks, then further extensions will be at 2 week intervals or ‘usual treatment’ as in control group)

High-risk participants will NOT be included in the PIRATE study cohort. They will continue with the current standard anti-VEGF therapy. Low-risk participants will be deemed anyone who meets the inclusion criteria WITHOUT having any of the high-risk criteria outlined.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
•Prior treatment of the study eye with intraocular anti-VEGF agents, verteporfin photodynamic therapy, other laser treatment, intraocular corticosteroids, surgical procedures (except cataract surgery greater than or equal to 30 days prior to screening)
•Systemic use of anti-VEGF agents within 3 months prior to the study entry period
•Active or suspected infection in or surrounding the study eye
•Peripapillary CNVM
•Active severe intraocular inflammation in the study eye
•Intraocular pressure greater than 28mmHg in study eye
•Ocular condition that might impact vision and confound study outcomes in the study eye (by the discretion of ophthalmology registrar or ophthalmologist)
•History of Avastin allergy or related intravitreal administration agents (e.g. povidone iodine, lidocaine, gutt. Iopidine, gutt. Chloramphenicol)
•Women who are pregnant, suspected to be pregnant or lactating
•Previous or concomitant participation in another clinical study with investigational medicinal product(s) within last 3 months
•Individuals who lack decision-making capacity who are not able to provide independent informed consent for the trial
•Any other patient deemed ineligible by investigator (ophthalmology registrar or ophthalmologist)

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 25002 0
New Zealand
State/province [1] 25002 0

Funding & Sponsors
Funding source category [1] 312209 0
Hospital
Name [1] 312209 0
Palmerston North Hospital
Country [1] 312209 0
New Zealand
Primary sponsor type
Hospital
Name
Palmerston North Hospital
Address
50 Ruahine Street, Roslyn, Palmerston North 4442
Country
New Zealand
Secondary sponsor category [1] 313734 0
None
Name [1] 313734 0
Address [1] 313734 0
Country [1] 313734 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 311590 0
Northern B Health and Disability Ethics Committee (FULL pathway)
Ethics committee address [1] 311590 0
Ethics committee country [1] 311590 0
New Zealand
Date submitted for ethics approval [1] 311590 0
01/09/2022
Approval date [1] 311590 0
Ethics approval number [1] 311590 0

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

Contacts
Principal investigator
Name 121634 0
Dr Antoine Bonnet
Address 121634 0
Palmerston North Hospital
Ophthalmology Department
50 Ruahine Street, Roslyn, 4442,
Palmerston North,
New Zealand
Country 121634 0
New Zealand
Phone 121634 0
+64 0273947946
Fax 121634 0
Email 121634 0
Contact person for public queries
Name 121635 0
Antoine Bonnet
Address 121635 0
Palmerston North Hospital
Ophthalmology Department
50 Ruahine Street, Roslyn, 4442,
Palmerston North,
New Zealand
Country 121635 0
New Zealand
Phone 121635 0
+64 0273947946
Fax 121635 0
Email 121635 0
Contact person for scientific queries
Name 121636 0
Antoine Bonnet
Address 121636 0
Palmerston North Hospital
Ophthalmology Department
50 Ruahine Street, Roslyn, 4442,
Palmerston North,
New Zealand
Country 121636 0
New Zealand
Phone 121636 0
+64 0273947946
Fax 121636 0
Email 121636 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17096Study protocol    384644-(Uploaded-11-09-2022-12-45-28)-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
SourceTitleYear of PublicationDOI
EmbasePalmerston North Interventional Rapid Avastin Treat and Extend (PIRATE) study protocol; Meeting the medical retina service needs of our ageing population.2023https://dx.doi.org/10.1136/bmjophth-2022-001192
N.B. These documents automatically identified may not have been verified by the study sponsor.