Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02243878 |
| Other study ID # |
UKCRN ID 18040 |
| Secondary ID |
ISRCTN12884465EM |
| Status |
Active, not recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
December 2014 |
| Est. completion date |
June 2024 |
Study information
| Verified date |
July 2023 |
| Source |
King's College Hospital NHS Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study investigates the use of radiation to treat wet age-related macular degeneration
(AMD). 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. Participants will be randomized to receive radiation (stereotactic radiotherapy) or
simulated placebo treatment (sham control). 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.
Ranibizumab is the standard anti-VEGF agent that is used to treat wet AMD. The study aims to
determine if stereotactic radiosurgery can maintain vision and reduce the need for such
regular anti-VEGF injections.
Description:
Age-related macular degeneration (AMD) leads more people to go blind than all other eye
diseases combined. 'Wet' AMD occurs when abnormal new blood vessels grow into the macula. The
macula is an area inside the back of the eye, which is tightly packed with the
light-sensitive cells that give fine central vision for driving, reading, facial recognition
etc. Most patients are treated with repeated injections of ranibizumab (Lucentis),
bevacizumab (Avastin) , or aflibercept (Eylea) into the eye (these drugs suppresses the new
vessel growth). Unsurprisingly, the need for hospital visits every 1-2 months, and regular
injections into the eye, is not favoured by patients.
The proposed study investigates the use of radiation to treat wet AMD. Radiation
preferentially damages proliferating cells, such as those forming the abnormal new blood
vessels. It has the potential to kill off the abnormal cells, unlike the injections which
just suppress the disease.
The radiation is delivered using a robotically controlled device that aims three beams of
radiation in through the white of eye, to overlap at the macula. Initial studies of
stereotactic radiotherapy (SRT) were promising, and established the best dose of radiation.
They showed that radiation has the potential to significantly reduce the need for injections.
Each injection costs the National Health Service (NHS) approximately £600, hence the
potential cost savings are substantial. For those who respond well, disease activity is
reduced, and injections can be eliminated or greatly reduced.
Eye charities have run focus groups of people with wet AMD to help set priorities, and
participants identified the burden of treating wet AMD as one of their most pressing
concerns, as it greatly restricts their freedom and quality of life. Repeated injections also
carry risks of rare but blinding complications, and long term they may possibly lead to other
eye diseases such as glaucoma and atrophy of the macula.
The preliminary SRT studies were not designed to determine if the visual outcome was the
same, better, or worse than standard injection therapy, and follow up was too short to
determine long term risks. A larger study is therefore required to confirm that SRT reduces
the number of injections and to determine if the visual outcomes are acceptable. There is
also a need for longer term safety monitoring, as radiation damage typically has a delayed
onset.
STAR will use ranibizumab as the anti-VEGF agent in both the treatment and control arms.
Ranibizumab was chosen over bevacizumab as it is licensed for use in the eye, and at present
bevacizumab is used in only a small minority of NHS hospitals, such that the results with
bevacizumab may be less generalisable. Bevacizumab may slow recruitment if prospective
participants are anxious about swapping to an off label treatment, and preliminary
discussions with prospective sites indicated some investigators would prefer to use
ranibizumab. Further, ranibizumab was used in the phase II INTREPID study (detailed below),
which helps inform the STAR statistical analysis. Aflibercept's mandated dosing in year 1
means it is not possible to determine if radiation reduces the need for anti-VEGF treatment,
the primary outcome measure.
Participants will be randomly allocated to dummy SRT (0 Gray dose) or live SRT (16 Gray).
Neither the treating doctor nor participant will know if a 0 or 16 Gray dose was given. SRT
will be performed in approximately 3 national treatment centres, but 25 NHS recruiting
hospitals will refer patients for SRT, and then review them afterwards, treating them with
ranibizumab as needed.
Participants will attend for examination monthly for two years. They will then revert to
standard NHS care, but with two further study visits - one at the end of year 3 and one at
the end of year 4. These two late safety visits are to exclude delayed radiation damage. At
the 24 monthly visits participants will have their vision tested on an eye chart, and a laser
scan (OCT) of their macula. If the vision drops or the OCT shows disease activity, then they
will receive an injection of ranibizumab. Participants will have imaging of the blood vessels
in the macula (angiography) at baseline and yearly thereafter for 4 years. The images will be
interpreted by an independent, specialist reading centre to quantify the effect of treatment,
to study the interaction of radiation and wet AMD, to look for subtle radiation damage, and
to subclassify disease to determine who responds best to SRT.
We predict that SRT will produce a similar, or possibly better vision than ranibizumab alone,
but with fewer injections. With 411 participants we will have 90% certainty that our results
are valid.
Participants will provide feedback using established questionnaires about how acceptable they
found SRT, their visual function, and their overall quality of life. Experienced health
economists will then look at the cost of treatment in relation to any improvement in quality
of life, to see if SRT is cost-effective.
The main outcomes we will monitor are the number of eye injections and visual function on an
eye chart, but several other observations will be made. In particular, we will monitor the
safety of treatment, any collateral damage caused by radiation, and the interactions between
radiation and diseased eye tissue.
If proven to be effective, SRT has the potential to save the NHS money, but more importantly,
it may reduce the burden of care faced by more than 250,000 people with wet AMD.
