Clinical efficacy and mechanistic evaluation of Eplerenone for central serous chorio-retinopathy – the VICI randomised trial

Andrew Lotery, Sobha Sivaprasad, Abby J O'Connell, Rosie A Harris, Lucy A Culliford, Angela Cree, Savita Madhusudhan, Helen Griffiths, Lucy A Ellis, Usha Chakravarthy, Tunde Peto, Chris A Rogers, Barnaby C Reeves

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Background In chronic central serous chorioretinopathy (CSCR), fluid accumulates in the subretinal space and causes permanent vision loss in ~30% of patients. There is no definitive treatment. Previous research suggests the mineralocorticoid receptor antagonist, eplerenone, is effective but it is not licensed for CSCR. Objectives To evaluate whether eplerenone was safe and superior to placebo for treating chronic CSCR. We also aimed to set up a biobank of DNA, serum and plasma samples from treatment-naïve participants for future research. Design A parallel randomised (1:1 ratio), multi-centre, double-masked, placebo-controlled superiority trial comparing eplerenone plus usual care with placebo plus usual care. Setting The trial took place in 22 NHS hospitals in the United Kingdom. Participants Eligible participants were aged ≥18 and ≤60 years with treatment naïve CSCR for ≥4 months, best corrected visual acuity (BCVA) >53 and <86 letters, no other conditions affecting visual acuity or contraindications to taking eplerenone or placebo. Interventions The intervention was oral eplerenone (25 mg/day for one week, increased to 50 mg/day for up to 12 months). Placebo was a lactose-filled capsule which appeared identical to over-encapsulated eplerenone tablets. To maintain blinding, participants in the placebo group followed the same dose escalation schedule as the eplerenone group. Usual care was included in both groups and was administered at the discretion of clinicians. Main outcome measures The primary outcome was BCVA at 12 months. Secondary outcomes were: low luminance visual acuity; central subfield retinal thickness; change in subretinal fluid (SRF) thickness; systemic and ocular adverse events; macular atrophy of the retinal pigment epithelium; sub-foveal choroidal thickness; choroidal permeability; resolution of SRF; time-to-recurrence of SRF; fundus fluorescein angiography phenotype; incidence of CSCR in the fellow eye; and patient-reported visual function. Randomisation and masking Participants were randomly allocated to eplerenone or placebo groups using a secure online system which returned a unique number corresponding to a bottle of investigational medicinal product (IMP). Participants, clinical care teams, pharmacists, outcome assessors and trial management were masked. Results Between 11/01/2017 and 22/02/2018, 57 participants were randomised to eplerenone and 57 to placebo; 57 and 54 participants respectively were included in the analysis of the primary outcome. Modelled mean BCVA at 12 months in the eplerenone and placebo groups was 80.4 (SD 4.6) and 79.5 (SD 4.5) letters, with an estimated difference between groups of 1.73 letters (95% confidence interval -1.12 to 4.57, p=0·24). Hyperkalaemia occurred in eight participants in each group (14%). No serious adverse events occurred in the eplerenone group; three unrelated serious adverse events occurred in the placebo group. Limitations Limitations included the inability to prevent co-treatments and discontinuation of IMP in the event of resolution or hyperkalaemia. Conclusions Eplerenone was safe but not superior to placebo in improving BCVA in people with chronic CSCR during 12 months follow-up. Future work Ophthalmologists should investigate alternative treatments for this condition, which remains complicated to treat.
Original languageEnglish
JournalHealth Technology Assessment
Publication statusAccepted/In press - 8 Jun 2020

Structured keywords

  • BTC (Bristol Trials Centre)

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