Abstract
Aims
Chronic central serous chorioretinopathy (CSCR) is poorly understood. Fluid accumulates in the subretinal space and retinal pigment epitheliopathy and neurosensory atrophy may develop. Permanent vision loss occurs in approximately one third of cases. There are no effective treatments for CSCR. Recent studies have shown the mineralocorticoid receptor antagonist, eplerenone, to be effective in resolving subretinal fluid and improving visual acuity. This trial aims to compare the safety and efficacy of eplerenone in patients with CSCR in a double-masked randomised placebo-controlled trial.
Methods
Patients are randomised 1:1 to receive eplerenone with usual care or placebo with usual care for 12 months; 25 mg per day for 1 week, then 50 mg per day up to 12 months (unless discontinued for safety or resolution of CSCR). Key eligibility criteria are: age 18–60 years, one eye with CSCR for ≥4 months duration, best-corrected visual acuity (BCVA) >53 and <86 letters and no previous treatment. The primary outcome is BCVA at 12 months. Secondary outcomes include resolution of subretinal fluid, development of macular atrophy, subfoveal choroidal thickness, changes in low luminance visual acuity, health-related quality of life and safety.
Conclusions
Recruitment is complete but was slower than expected. We maintained the eligibility criteria to ensure participants had ‘true’ CSCR and recruited additional centres. Effective distribution of the investigational medicinal product (IMP) was achieved by implementing a database to manage ordering and accountability of IMP packs. The results will provide adequately powered evidence to inform clinical decisions about using eplerenone to treat patients with CSCR.
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Acknowledgements
We would like to acknowledge the Macular Society and Fight for Sight for their feedback on the patient information leaflet and the DMSC and TSC for their oversight of the trial. The independent DMSC is formed of a Chairperson, two consultant ophthalmologists and one consultant cardiologist. The independent TSC is formed of a Chairperson, two consultant ophthalmologists, a consultant cardiologist, an ophthalmic statistician and patient and public involvement representatives; other TSC members with observer status represent the trial management team and the Sponsor.
Funding
This project is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (ref: 13/94/15), with contributions from the CSO in Scotland and NISCHR in Wales and the HSC R&D Division, Public Health Agency in Northern Ireland. The trial is sponsored by University Hospital Southampton NHS Foundation Trust, Southampton, UK. This study was designed and delivered in collaboration with the Clinical Trials and Evaluation Unit (CTEU), a UKCRC registered clinical trials unit which, as part of the Bristol Trials Centre, is in receipt of National Institute for Health Research CTU support funding.
Author contributions
AL conceived the trial; AL, SS, BCR, AC and CR obtained funding; AL, SS, BCR and CR designed the trial; AW, LE and LC managed the trial with input from AL, SS, BCR and CR; UC, SE and FB-C provided expert input; AC and AL set up the biobank; AW wrote the first draft of the manuscript. All authors reviewed the manuscript and amended/approved the final version
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AW, LC, LE, CAR, AC, SE and BCR have no conflicts of interest. FB-C is an inventor on a patent protecting the use of MR antagonists in CSCR. SS has received research grants, travel grants, and speaker fees from Novartis, Bayer, Allergan, Roche, Heidelberg Engineering, and Optos. AL has received travel grants and speaker fees from Bayer and Roche.
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Willcox, A., Culliford, L., Ellis, L. et al. Clinical efficacy of eplerenone versus placebo for central serous chorioretinopathy: study protocol for the VICI randomised controlled trial. Eye 33, 295–303 (2019). https://doi.org/10.1038/s41433-018-0212-2
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DOI: https://doi.org/10.1038/s41433-018-0212-2
