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Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease for more than 4 months (VICI): a randomised, double-blind, placebo-controlled trial

Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease for more than 4 months (VICI): a randomised, double-blind, placebo-controlled trial
Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease for more than 4 months (VICI): a randomised, double-blind, placebo-controlled trial
Background
In chronic central serous chorioretinopathy (CSCR), fluid accumulates in the subretinal space. CSCR is a common visually disabling condition that develops in individuals up to 60 years of age, and there is no definitive treatment. Previous research suggests the mineralocorticoid receptor antagonist, eplerenone, is effective for treating CSCR; however, this drug is not licensed for the treatment of patients with CSCR. We aimed to evaluate whether eplerenone was superior to placebo in terms of improving visual acuity in patients with chronic CSCR.

Methods
This randomised, double-blind, parallel-group, multicentre placebo-controlled trial was done at 22 hospitals in the UK. Participants were eligible if they were aged 18–60 years and had had treatment-naive CSCR for 4 months or more. Patients were randomly assigned (1:1) to either the eplerenone or the placebo group by a trial statistician through a password-protected system online. Allocation was stratified by best-corrected visual acuity (BCVA) and hospital. Patients were given either oral eplerenone (25 mg/day for 1 week, increasing to 50 mg/day for up to 12 months) plus usual care or placebo plus usual care for up to 12 months. All participants, care teams, outcome assessors, pharmacists, and members of the trial management group were masked to the treatment allocation. The primary outcome was BCVA, measured as letters read, at 12 months. All outcomes apart from safety were analysed on a modified intention-to-treat basis (participants who withdrew consent without contributing a post-randomisation BCVA measurement were excluded from the primary analysis population and from most secondary analysis populations). The trial is registered with ISRCTN, ISRCTN92746680, and is completed.

Findings
Between Jan 11, 2017, and Feb 22, 2018, we enrolled and randomly assigned 114 patients to receive either eplerenone (n=57) or placebo (n=57). Three participants in the placebo group withdrew consent without contributing a post-randomisation BCVA measurement and were excluded from the primary outcome analysis population. All patients from the eplerenone group and 54 patients from the placebo group were included in the primary outcome. Modelled mean BCVA at 12 months was 79·5 letters (SD 4·5) in the placebo group and 80·4 letters (4·6) in the eplerenone group, with an adjusted estimated mean difference of 1·73 letters (95% CI −1·12 to 4·57; p=0·24) at 12 months. Hyperkalaemia occurred in eight (14%) patients in each group. No serious adverse events were reported in the eplerenone group and three unrelated serious adverse events were reported in the placebo group (myocardial infarction [anticipated], diverticulitis [unanticipated], and metabolic surgery [unanticipated]).

Interpretation
Eplerenone was not superior to placebo for improving BCVA in people with chronic CSCR after 12 months of treatment. Ophthalmologists who currently prescribe eplerenone for CSCR should discontinue this practice.

Funding
Efficacy and Mechanism Evaluation Programme, and National Institute for Health Research and Social Care.
0140-6736
294-303
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Sivaprasad, Sobha
7cd590d6-18f0-4ae1-8ace-4b35833c2f03
O'Connell, Abby
c1fc72d1-2047-40da-a19b-7915daae9d76
Harris, Rosie
13be2410-96b0-4c66-84da-de3aa51020a4
Culliford, Lucy
2ebe9e38-51e1-4390-985a-3519410f3856
Ellis, Lucy
624767d4-eab6-44f1-8f0c-3b89d4e69979
Cree, Angela
6724b71b-8828-4abb-971f-0856c2af555e
Madhusudhan, Savita
d4ba51be-8292-4ce6-9953-503c1a6e5e3c
Behar-Cohen, Francine
538bbb9e-3afa-46b9-8ace-6d506613153c
Chakravarthy, Usha
2c06cdaf-94c0-409a-8eff-2f624c120a5e
Peto, Tunde
e5511bbd-2ef8-4465-a2b3-46c8cc3ce63e
Rogers, Chris A.
1074c268-aced-471a-95fe-ad3e0067e605
Reeves, Barnaby C.
3d10eab6-24a5-41c7-8ecc-8b5ace0f25ff
VICI trial investigators
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Sivaprasad, Sobha
7cd590d6-18f0-4ae1-8ace-4b35833c2f03
O'Connell, Abby
c1fc72d1-2047-40da-a19b-7915daae9d76
Harris, Rosie
13be2410-96b0-4c66-84da-de3aa51020a4
Culliford, Lucy
2ebe9e38-51e1-4390-985a-3519410f3856
Ellis, Lucy
624767d4-eab6-44f1-8f0c-3b89d4e69979
Cree, Angela
6724b71b-8828-4abb-971f-0856c2af555e
Madhusudhan, Savita
d4ba51be-8292-4ce6-9953-503c1a6e5e3c
Behar-Cohen, Francine
538bbb9e-3afa-46b9-8ace-6d506613153c
Chakravarthy, Usha
2c06cdaf-94c0-409a-8eff-2f624c120a5e
Peto, Tunde
e5511bbd-2ef8-4465-a2b3-46c8cc3ce63e
Rogers, Chris A.
1074c268-aced-471a-95fe-ad3e0067e605
Reeves, Barnaby C.
3d10eab6-24a5-41c7-8ecc-8b5ace0f25ff

Lotery, Andrew, Sivaprasad, Sobha, O'Connell, Abby, Harris, Rosie, Culliford, Lucy, Ellis, Lucy, Cree, Angela, Madhusudhan, Savita, Behar-Cohen, Francine, Chakravarthy, Usha, Peto, Tunde, Rogers, Chris A. and Reeves, Barnaby C. , VICI trial investigators (2020) Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease for more than 4 months (VICI): a randomised, double-blind, placebo-controlled trial. The Lancet, 395 (10220), 294-303. (doi:10.1016/S0140-6736(19)32981-2).

Record type: Article

Abstract

Background
In chronic central serous chorioretinopathy (CSCR), fluid accumulates in the subretinal space. CSCR is a common visually disabling condition that develops in individuals up to 60 years of age, and there is no definitive treatment. Previous research suggests the mineralocorticoid receptor antagonist, eplerenone, is effective for treating CSCR; however, this drug is not licensed for the treatment of patients with CSCR. We aimed to evaluate whether eplerenone was superior to placebo in terms of improving visual acuity in patients with chronic CSCR.

Methods
This randomised, double-blind, parallel-group, multicentre placebo-controlled trial was done at 22 hospitals in the UK. Participants were eligible if they were aged 18–60 years and had had treatment-naive CSCR for 4 months or more. Patients were randomly assigned (1:1) to either the eplerenone or the placebo group by a trial statistician through a password-protected system online. Allocation was stratified by best-corrected visual acuity (BCVA) and hospital. Patients were given either oral eplerenone (25 mg/day for 1 week, increasing to 50 mg/day for up to 12 months) plus usual care or placebo plus usual care for up to 12 months. All participants, care teams, outcome assessors, pharmacists, and members of the trial management group were masked to the treatment allocation. The primary outcome was BCVA, measured as letters read, at 12 months. All outcomes apart from safety were analysed on a modified intention-to-treat basis (participants who withdrew consent without contributing a post-randomisation BCVA measurement were excluded from the primary analysis population and from most secondary analysis populations). The trial is registered with ISRCTN, ISRCTN92746680, and is completed.

Findings
Between Jan 11, 2017, and Feb 22, 2018, we enrolled and randomly assigned 114 patients to receive either eplerenone (n=57) or placebo (n=57). Three participants in the placebo group withdrew consent without contributing a post-randomisation BCVA measurement and were excluded from the primary outcome analysis population. All patients from the eplerenone group and 54 patients from the placebo group were included in the primary outcome. Modelled mean BCVA at 12 months was 79·5 letters (SD 4·5) in the placebo group and 80·4 letters (4·6) in the eplerenone group, with an adjusted estimated mean difference of 1·73 letters (95% CI −1·12 to 4·57; p=0·24) at 12 months. Hyperkalaemia occurred in eight (14%) patients in each group. No serious adverse events were reported in the eplerenone group and three unrelated serious adverse events were reported in the placebo group (myocardial infarction [anticipated], diverticulitis [unanticipated], and metabolic surgery [unanticipated]).

Interpretation
Eplerenone was not superior to placebo for improving BCVA in people with chronic CSCR after 12 months of treatment. Ophthalmologists who currently prescribe eplerenone for CSCR should discontinue this practice.

Funding
Efficacy and Mechanism Evaluation Programme, and National Institute for Health Research and Social Care.

Text
VICI Trial Main Results Manuscript v3.0 Accepted - Accepted Manuscript
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Text
VICI Trial Supplementary Appendix v2.0 Accepted - Accepted Manuscript
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Image
VICI trial - Figure 1 - CONSORT diagram - Accepted Manuscript
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Image
VICI trial - Figure 2 - Primary outcome v2 - Accepted Manuscript
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More information

Accepted/In Press date: 19 November 2019
e-pub ahead of print date: 23 January 2020
Published date: 25 January 2020

Identifiers

Local EPrints ID: 436693
URI: http://eprints.soton.ac.uk/id/eprint/436693
ISSN: 0140-6736
PURE UUID: 91f54c85-85b2-48be-8725-fbe6630e0df7
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for Angela Cree: ORCID iD orcid.org/0000-0002-1987-8900

Catalogue record

Date deposited: 20 Dec 2019 18:31
Last modified: 16 Aug 2024 04:02

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Contributors

Author: Andrew Lotery ORCID iD
Author: Sobha Sivaprasad
Author: Abby O'Connell
Author: Rosie Harris
Author: Lucy Culliford
Author: Lucy Ellis
Author: Angela Cree ORCID iD
Author: Savita Madhusudhan
Author: Francine Behar-Cohen
Author: Usha Chakravarthy
Author: Tunde Peto
Author: Chris A. Rogers
Author: Barnaby C. Reeves
Corporate Author: VICI trial investigators

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