StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR)
| ISRCTN | ISRCTN12884465 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12884465 |
| IRAS number | 86810 |
| ClinicalTrials.gov number | NCT02243878 |
| Secondary identifying numbers | IRAS 86810 |
- Submission date
- 28/11/2014
- Registration date
- 13/12/2014
- Last edited
- 01/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Eye Diseases
Plain English Summary
Background and study aims
Age-related macular degeneration (AMD) is a painless eye condition that leads to loss of central vision. There are two main types of AMD, called dry AMD and wet AMD. Wet AMD is more serious and without treatment, vision can deteriorate within days. This study investigates the use of radiation to treat wet AMD, called stereotactic radiosurgery. The radiation is delivered using a robotically controlled device that projects overlapping beams of radiation onto the macula, the part of the eye that is affected by wet AMD. This study aims to determine if stereotactic radiosurgery can maintain vision and reduce the need for regular injections of ranibizumab (the standard anti-VEGF drug used to treat wet AMD).
Who can participate?:
Males and females aged 50 years or over with wet AMD requiring anti-VEGF treatment at the time of entry to the study.
What does the study involve?
Participants will be randomly allocated to receive either radiation (stereotactic radiotherapy) or simulated placebo (sham) treatment. They will be followed up regularly for two years, and then again at the end of three and four years for a safety visit. Participants will also receive injections of ranibizumab (Lucentis) into their eye if their wet AMD is active.
What are the possible benefits and risks of participating?
The main benefit of stereotactic radiotherapy is that it may reduce the number of eye injections that people require, or in some cases eliminate them entirely. Previous studies have suggested that the patients who will be eligible for the study would obtain a better vision outcome with radiotherapy (with injections as needed) than with injections alone. The main risk of radiation is that it can sometimes damage the healthy tissue in the macula and thereby damage vision. Subtle changes to the macula can sometimes be seen using specialised testing (fluorescein angiography) but in the majority of people this does not affect the vision.
Where is the study run from?
King's College Hospital (UK).
When is the study starting and how long is it expected to run for?
Recruitment to the study will begin in December 2014 and continue for approximately 41 months. Each participant will be in the study for 4 years.
Who is funding the study?
NIHR Efficacy and Mechanism Evaluation Programme (UK).
Who is the main contact?
Mr Tim Jackson
t.jackson1@nhs.net
Contact information
Scientific
King’s College London
Department of Ophthalmology
King’s College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
| Phone | +44 (0)20 3299 1297 |
|---|---|
| t.jackson1@nhs.net |
Public
Ophthalmology Department
Research Office
1st Floor, Normanby Building
King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
| Phone | +44 (0)20 3299 1297 |
|---|---|
| ritidesai@nhs.net |
Study information
| Study design | Randomised double-masked sham-controlled pivotal clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR): a randomised, double-masked, sham-controlled, clinical trial comparing low-voltage X-ray irradiation with as needed ranibizumab to as needed ranibizumab monotherapy |
| Study acronym | STAR |
| Study hypothesis | The study’s primary hypothesis is that the mean number of ranibizumab injections during the first 24 months after randomization will be less in the SRT group than in the sham group. The secondary hypothesis is that participants who undergo SRT will have a non-inferior visual outcome compared with those in the sham group. |
| Ethics approval(s) | NRES Committee London - City & East, REC ref: 13/LO/1207 |
| Condition | Retinal disease/age-related macular degeneration |
| Intervention | Participants in the treatment arm will receive 16 Gray stereotactic radiotherapy (SRT) with a concomitant injection of ranibizumab. |
| Intervention type | Device |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Not provided at time of registration |
| Primary outcome measure | The primary outcome is the mean number of ranibizumab injections over 24 months. SRT will be considered superior to sham if the mean number of injections in the SRT group is statistically less than (one-sided p<0.025) the mean in the sham group. |
| Secondary outcome measures | SRT will be considered non-inferior to sham treatment if the lower bound of the 95% confidence interval for the difference in mean change in ETDRS VA at 24 months, between the SRT and sham groups, is no greater than 5 letters. |
| Overall study start date | 01/12/2014 |
| Overall study end date | 30/06/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 411 |
| Total final enrolment | 411 |
| Participant inclusion criteria | Current participant inclusion criteria as of 01/08/2018: 1. Participants must have neovascular AMD in the study eye, for which they have received at least three prior intravitreal injections of either bevacizumab (Avastin), aflibercept (Eylea), ranibizumab (Lucentis) or pegaptanib (Macugen) 2. Participants must have received an anti-VEGF injection in the study eye within 3 months prior to enrolment 3. Participants must require treatment with anti-VEGF therapy at the time of enrolment, due to OCT evidence of subretinal fluid and/or cystoid macular oedema, and have a macular volume that is greater than a pre-defined threshold that varies for each different make of SD-OCT machine 4. Participants must be at least 50 years of age Previous participant inclusion criteria: 1. Participants must have neovascular AMD in the study eye, for which they have received at least three prior intravitreal injections of either bevacizumab (Avastin), aflibercept (Eylea), ranibizumab (Lucentis) or pegaptanib (Macugen) 2. Participants must have received an anti-VEGF injection in the study eye within 3 months prior to enrolment 3. Participants must require treatment with anti-VEGF therapy at the time of enrolment, due to OCT evidence of subretinal fluid and/or cystoid macular oedema, and a macular volume that is greater than the 95th percentile of normal for the SD-OCT machines used in the investigational sites 4. Participants must be at least 50 years of age |
| Participant exclusion criteria | Current participant exclusion criteria as of 01/08/2018: 1. Disciform scarring that involves the fovea, in the study eye 2. Visual acuity worse than 6/96 (24 ETDRS letters) in the study eye 3. Lesion size greater than 4 mm in greatest linear dimension, or greater than 2 mm from the centre of the fovea to the furthest point on the lesion perimeter 4. An axial length of less than 20 mm, or greater than 26 mm, in the study eye 5. Contraindication or sensitivity to contact lens application, including recurrent corneal erosions, in the study eye 6. Type 1 or Type 2 diabetes mellitus 7. Retinopathy in the study eye 8. Prior or current therapies in the study eye for age-related macular degeneration, other than anti-VEGF agents, including submacular surgery, subfoveal thermal laser photocoagulation, photodynamic therapy (PDT), or transpupillary thermotherapy (TTT) 9. Presence of an intravitreal device in the study eye 10. Previous radiation therapy to the study eye, head or neck with the exception of radio-iodine treatment for hyperthyroidism, epimacular brachytherapy to the non-study eye, or Oraya SRT to the non-study eye 11. Inadequate pupillary dilation or significant media opacities in the study eye, including cataract, which may interfere with visual acuity testing, the clinical evaluation of the posterior segment, or fundus imaging 12. Study eyes with CNV due to causes other than AMD, including presumed ocular histoplasmosis syndrome (POH), angioid streaks, multifocal choroiditis, choroidal rupture, and pathological myopia (greater than 8 Dioptres spherical equivalent). Participants with retinal angiomatous proliferation (RAP) or idiopathic polypoidal choroidal vasculopathy (IPCV) are not excluded 13. Known allergy to intravenous fluorescein, ICG or intravitreal ranibizumab 14. Intraocular surgery or laser-assisted in situ keratomileusis (LASIK) in the study eye within 12 weeks prior to enrolment 15. Prior pars plana vitrectomy in the study eye 16. Current participation in another interventional clinical trial, or participation in such a clinical trial within the last six months 17. Unwilling, unable, or unlikely to return for scheduled follow-up for the duration of the trial 18. Women who are pregnant at the time of radiotherapy 19. Participants with an implantable cardioverter defibrillator (ICD) or pacemaker implant (or any implanted device) where the device labelling specifically contraindicates patients undergoing X-ray 20. Any other condition, which in the judgment of the investigator, would prevent the participant from granting informed consent or completing the study, such as dementia and mental illness (including generalized anxiety disorder and claustrophobia) Previous participant exclusion criteria: 1. Disciform scarring that involves the fovea, in the study eye 2. Geographic atrophy that involves the fovea, or an area of geographic atrophy that is more than 500 microns in greatest diameter, immediately adjacent to the fovea, in the study eye 3. Visual acuity worse than 6/96 (24 ETDRS letters) in the study eye 4. Lesion size greater than 4 mm in greatest linear dimension, or greater than 2 mm from the centre of the fovea to the furthest point on the lesion perimeter 5. Distance from the center of the fovea to the nearest edge of the optic disc less than 3 mm in the study eye (this distance is confirmed by the Oraya SRT device software immediately prior to treatment) 6. An axial length of less than 20 mm, or greater than 26 mm, in the study eye 7. Contraindication or sensitivity to contact lens application, including recurrent corneal erosions, in the study eye 8. Type 1 or Type 2 diabetes mellitus 9. Retinopathy in the study eye 10. Prior or current therapies in the study eye for age-related macular degeneration, other than anti-VEGF agents, including submacular surgery, subfoveal thermal laser photocoagulation, photodynamic therapy (PDT), or transpupillary thermotherapy (TTT) 11. Presence of an intravitreal device in the study eye 12. Previous radiation therapy to the study eye, head or neck with the exception of radio-iodine treatment for hyperthyroidism, epimacular brachytherapy to the non-study eye, or Oraya SRT to the non-study eye 13. Inadequate pupillary dilation or significant media opacities in the study eye, including cataract, which may interfere with visual acuity testing, the clinical evaluation of the posterior segment, or fundus imaging 14. Likely to need cataract surgery in the study eye within two years of enrolment 15. Study eyes with CNV due to causes other than AMD, including presumed ocular histoplasmosis syndrome (POH), angioid streaks, multifocal choroiditis, choroidal rupture, and pathological myopia (greater than 8 Dioptres spherical equivalent). Participants with retinal angiomatous proliferation (RAP) or idiopathic polypoidal choroidal vasculopathy (IPCV) are not excluded 16. Known allergy to intravenous fluorescein, ICG or intravitreal ranibizumab 17. Intraocular surgery or laser-assisted in situ keratomileusis (LASIK) in the study eye within 12 weeks prior to enrolment 18. Prior pars plana vitrectomy in the study eye 19. Current participation in another interventional clinical trial, or participation in such a clinical trial within the last six months 20. Unwilling, unable, or unlikely to return for scheduled follow-up for the duration of the trial 21. Women who are pregnant at the time of radiotherapy 22. Participants with an implantable cardioverter defibrillator (ICD) or pacemaker implant (or any implanted device) where the device labelling specifically contraindicates patients undergoing X-ray 23. Any other condition, which in the judgment of the investigator, would prevent the participant from granting informed consent or completing the study, such as dementia and mental illness (including generalized anxiety disorder and claustrophobia) |
| Recruitment start date | 01/12/2014 |
| Recruitment end date | 31/12/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Normanby Building
Denmark Hill
London
SE5 9RS
United Kingdom
Lower Maudlin Street
Bristol
BS1 2LX
United Kingdom
Portsmouth Road
Frimley
Camberley
GU16 7UJ
United Kingdom
Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Haslingden Road
Blackburn
BB2 3HH
United Kingdom
Brighton
BN2 5BF
United Kingdom
Willesborough
Ashford
TN24 0LZ
United Kingdom
Pield Heath Road
Uxbridge
UB8 3NN
United Kingdom
Whipps Cross Road
London
E11 1NR
United Kingdom
Harlow
CM20 1QX
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Colchester
CO3 3NB
United Kingdom
Huddersfield Road
Halifax
HX3 0PW
United Kingdom
Aylesbury
HP21 8AL
United Kingdom
Gorleston
Great Yarmouth
NR31 6LA
United Kingdom
Derby
DE22 3NE
United Kingdom
Romford
RM7 0AG
United Kingdom
Bordesley Green
Birmingham
B9 5SS
United Kingdom
Park Royal
London
NW10 7NS
United Kingdom
Salisbury
SP2 8BJ
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Carshalton
SM5 1AA
United Kingdom
Lincoln
LN2 5QY
United Kingdom
Crewe
CW1 4QJ
United Kingdom
Yeovil
BA21 4AT
United Kingdom
Dorchester
DT1 2JY
United Kingdom
Huntingdon
PE29 6NT
United Kingdom
Sponsor information
Hospital/treatment centre
King’s College Hospital
Denmark Hill
London
SE5 9RS
England
United Kingdom
| Website | https://www.kch.nhs.uk/research |
|---|---|
"ROR" |
https://ror.org/01n0k5m85 |
University/education
Strand Campus
The Strand
London
WC2R 2LS
England
United Kingdom
| Website | http://www.kcl.ac.uk/index.aspx |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 24/11/2016 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 1.9 | 25/01/2019 | 01/11/2023 | No | No |
Additional files
Editorial Notes
01/11/2023: The following changes were made to the trial record:
1. Uploaded protocol (not peer-reviewed) as an additional file.
2. The IRAS number was added.
3. The study participating centres University Hospitals Bristol NHS Trust, Frimley Park Hospital, Maidstone and Tunbridge Wells NHS Trust, The Royal Wolverhampton NHS Trust, East Lancashire Hospitals NHS Trust, The Sussex Eye Hospital, William Harvey Hospital (ashford), Hillingdon Hospital, Whipps Cross University Hospital NHS Trust, Princess Alexandra Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust, Essex County Hospital, Opthalmology (calderdale Royal Hospital), Stoke Mandeville Hospital, James Paget University Hospitals NHS Foundation Trust, Royal Derby Hospital, Queens Hospital, Birmingham Heartlands Hospital, Central Middlesex Hospital NHS Trust, Salisbury District Hospital, Cambridge University Hospital, St Helier Hospital, Lincoln County Hospital, Leighton Hospital, Yeovil District Hospital, Dorset County Hospital, and Hinchingbrooke Hospital were added.
10/03/2020: IPD sharing statement added.
24/01/2020: Total final enrolment number added.
08/10/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/09/2019 to 31/12/2019.
2. The overall end date was changed from 31/03/2024 to 30/06/2024.
3. The intention to publish date was changed from 31/03/2025 to 30/06/2025.
01/08/2018: The following updates have been made to the trial record:
1. The recruitment end date has been changed from 30/04/2018 to 30/09/2019
2. The overall trial end date has been changed from 31/10/2022 to 31/03/2024
3. The intention to publish date has been added
4. The participant inclusion criteria have been updated
5. The participant exclusion criteria have been updated
25/11/2016: Publication reference added.
