The MATE study
Research type
Research Study
Full title
Treating neovascular age-related Macular Degeneration with Aflibercept: a pilot 24 month, multi-centre randomized controlled trial comparing Standard Care with an individualised Treat and Extend regimen.
IRAS ID
178790
Contact name
Richard Gale
Contact email
Sponsor organisation
York Teaching Hospital NHS Foundation Trust
Eudract number
2015-002302-36
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Research Summary
MATE study is a multicentred, two armed, pilot randomised control trial comparing two treatment regimen of aflibercept for neovascular age related macular degeneration.
This pilot study will mainly assess the processes of a main study to ensure recruitment, randomisation, treatment and follow up assessments can run smoothly and safely.
The participants will be randomised to receive either Standard care or a treat and extend regimen. Both groups will receive intravitreal 2mg aflibercept. The Standard care will receive initial 3 doses of monthly aflibercept injections followed by 8 weekly treatments for the first year with an opportunity to extend the treatment intervals in the second year of treatment at the discretion of the treating physician.
The treat and extend regimen comprises of initial 3 doses of monthly aflibercept followed by extension of treatment intervals at the discretion of the treatment physician until an interval appropriate for the individual is found. This has the potential to allow a minimum number of visits, on each of which a treatment is administered, whilst maintaining an acceptable efficacy. All participants have an equal (50%) chance of being randomised to either of the groups.
This study has been designed to mirror a phase 3 randomised control trial and the results from this study will be used to inform a future main study. The potential benefits of this study are a reduction in the burden of treatment to both the individual and provider.Summary of Results
Background Age-related macular degeneration (AMD) is the leading cause of sight loss in the developed world (1) affecting an estimated 288 million individuals by the year 2040 (2). The prevalence of late forms of AMD, including wet AMD, increases with age with an estimated prevalence of 263,000 cases in the UK alone (3). Wet AMD is characterised by the build-up of fluid and blood in the central macular at the back of the eye, this part is essential for reading and recognising faces. This build-up of fluid and blood can be measured in the clinic as it causes an increase in the thickness of the back of the eye.
Although there is no current cure for AMD, the gold-standard care for wet AMD involves regular injections into the eye of a drug which halts the build-up of fluid and blood. Treatment has been shown to improve vision as measured by the number of letters read on a letter chart and also reduces the build-up of fluid and blood as measured by the thickness of the back of the eye. Typically, treatment is given monthly for the first three injections, following one of two regimens thereafter. Current standard care for treatment follows a monthly regimen for the first year with treatment as-required thereafter based on clinical assessment. However, recently there has been a shift towards a treat and extend regimen whereby treatment is given at every clinical visit but the interval between visits can be changed to find a frequency most suitable for each patient, thus this is an individualised treatment regimen. Treat and extend treatment regimens aim to reduce the frequency of visits and injections for each patient whilst minimising the loss of vision.
Many studies have compared the benefits of these two regimens for two of the most common treatments used for wet AMD, drugs called ranibizumab and bevacizumab. The results of these studies show that both drugs maintain vision with fewer visits for the patient (4–7). The current gap in the literature is a lack of evidence for the drug called aflibercept which has been shown to be a longer acting drug (8). Therefore, the aim of the MATE study was to carry out a small pilot study comparing the benefits of two treatment regimens for patients with wet age-related macular degeneration, providing information to perform a large-scale clinical trial.
The MATE Study
Forty-four patients diagnosed with wet AMD were recruited from six NHS medical retina units across the United Kingdom between December 2015 and January 2019. Written informed consent was obtained from all patients and ethical approval granted by the relevant Research and Ethics Committees. The study followed the tenets of the Declaration of Helsinki. This study was also extensively reviewed by the Research and Development group at York and Scarborough Teaching Hospitals NHS Foundation Trust, which includes public contributors.
Patients were randomly allocated to either the standard care or treat and extend group and followed for 2 years. The primary aim was to evaluate whether the MATE pilot study could be performed effectively to inform a large-scale clinical trial by assessing the recruitment rate, withdrawal rate and conducting interviews with key study staff identifying issues relating to recruitment. The second aim was to report the outcomes of the two treatment regimens and the burden to patients and services by assessing changes in vision, changes in the thickness of the back of the eye and the number of visits and treatments. Patient reported quality of life and treatment satisfaction between the two treatment regimens were also measured over the 2-year study period.
Addressing the primary aim, the overall recruitment rate was 3.07 patients per month with a 15% withdrawal/non-completion rate; this is in line with previous studies. Interviews with key study staff highlighted that with some minor changes to the study protocol to make recruitment easier, the MATE study could effectively transition to a large-scale clinical trial.
Addressing the secondary aim, the results suggest there were bigger improvements for patients in the treat and extend group compared with the standard care group after 2 years of treatment. On average, patients in the treat and extend group could read more letters on a standard letter chart, meaning their vision had improved slightly. There was also a bigger reduction in thickness of the back of the eye meaning that treatment had reduced the build-up of fluid and blood. Considering the burden to patients, those in the treat and extend group had more treatments but fewer clinical visits over 2 years compared to the standard care group. Over 2 years, patient reported quality of life appeared to slightly improve with treatment satisfaction remaining stable for both treatment groups.
The MATE Extension Study
At the end of the MATE study, patients were asked if they would like to participate for a further 2 years of study to obtain more in depth information on the benefits of aflibercept treatment for wet AMD over a longer time period. Twenty-six patients from the original cohort consented to join the MATE Extension Study for an additional 2 years. Patients were no longer split based on the original study grouping and were combined to form one group with the primary aim to report on the long-term treatment outcomes over 4 years. Changes in vision and changes in thickness of the back of the eye were measured along with the number of treatments and visits to measure the treatment burden. Patient reported quality of life and treatment satisfaction were also measured.
Whilst there were initial improvements in vision after 12 months, there were slight reductions in the average number of letters read at 4 years, indicating that vision had got worse over time. However, long-term treatment continued to reduce the thickness of the back of the eye meaning there was a reduction in the build-up of fluid and blood. Although patient reported quality of life showed a decrease in general, questions relating specifically to AMD and treatment satisfaction showed a slight improvement over the 4 years.
Conclusion
To conclude, the MATE study has provided a unique insight into the recruitment phase and conduct of running a pilot study. We found that with some minor changes to the current study protocol, the MATE study could be an effective large-scale clinical trial. Comparing the two treatment regimens, treatment outcomes appeared better for the treat and extend group compared to the standard care group, with reduced treatment burden after 2 years. As is the case with pilot studies, the small number of patients included in the two groups in this study means that calculating significance from the results can be challenging. Importantly, the results we found do suggest that it would be worth further investigation in a larger group of wet AMD patients to confirm these findings. Data from the MATE Extension Study reveal that over 4 years, whilst there was a decrease in thickness of the back of the eye, patients vision actually got worse. Despite general quality of life reducing, AMD-specific quality of life and treatment satisfaction remained relatively stable over 4 years.Dissemination of Results
Outcomes from the MATE studies have been presented at research conferences both nationally and internationally. The data have also been prepared as three separate manuscripts which are currently being submitted for publication at leading ophthalmology journals. All disseminations have been extensively reviewed by members of the research team and the Research and Development group at York and Scarborough Teaching Hospitals NHS Foundation Trust, which includes public contributors.
References
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Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
15/YH/0286
Date of REC Opinion
20 Aug 2015
REC opinion
Further Information Favourable Opinion