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

Phase 3

Completed

• Conditions: Specialty: Ophthalmology, Primary sub-specialty: Glaucoma; UKCRC code/ Disease: Eye/ Disorders of choroid and retina; Eye Diseases; Central serous chorio-retinopathy

• Registration Number: ISRCTN92746680
• Lead Sponsor: niversity Hospital Southampton NHS Foundation Trust

Brief Summary

2020 Results article in https://pubmed.ncbi.nlm.nih.gov/31982075/ results (added 24/01/2020) 2021 Results article in https://doi.org/10.3310/eme08020 (added 14/06/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-05-06
• Study Completion: 2019-07-31
• Last Update Posted: 26 June 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

Inclusion criteria as of 12/01/2017:
1. Aged between 18 and 60 years
2. Visual impairment due to CSCR of = 4 months duration defined as:
2.1. Subfoveal presence of SRF on OCT
AND
2.2. Characteristic appearance of CSCR on FFA and Indocyanine-green angiography (ICGA).
AND
2.3. Investigator believes that there is sufficient evidence from patient history, case note documentation or appearance of the macula that CSCR has been present for at least 4 months
3. Women must be willing to use effective contraception, be surgically sterile or post-menopausal for >12 months
4. Able to provide written informed consent

The following additional inclusions apply to a study eye only (i.e. they may be present for a non-study eye):
1. A study eye should have an Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA score greater than 53 letters and less than 86 letters
2. A study eye should have clear ocular media and adequate pupillary dilatation to permit photography

It is rare but not impossible for patients to present with CSCR in both eyes or CSCR may develop in the fellow eye during the trial. We propose to measure eye-specific outcomes such as BCVA in both eyes throughout the trial, designating eyes as study eyes or not. Statistical analyses will take into account the availability of data for two eligible eyes in one patient. If both eyes present with CSCR at baseline, the clinical trial site will decide which is the primary eye and this eye will have retinal imaging performed first. The primary eye would usually be the one with most active disease/most subretinal fluid. It will be identified by OCT imaging and subsequent investigations such as fluorescein and indocyanine green angiography will then be performed initially on this eye. If a patient presents with one affected eye and the fellow eye subsequently develops CSCR the eye first affected will always be the primary study eye.

Original inclusion criteria:
1. Aged between 18 and 60 years
2. Visual impairment due to central serous chorio-retinopathy (CSCR) of = 4 months duration defined as:
2.1. Subfoveal presence of sub-retinal fluid (SRF) on OCT
AND
2.2. Characteristic appearance of CSCR on FFA and Indocyanine-green angiography (ICGA).
3. Women must be willing to use effective contraception, be surgically sterile or post-menopausal for >12 months
4. Able to provide written informed consent

The following additional inclusions apply to a study eye only (i.e. they may be present for a non-study eye):
5. A study eye should have an Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA score greater than 53 letters and less than 79 letters
6. A study eye should have clear ocular media and adequate pupillary dilatation to permit photography

It is rare but not impossible for patients to present with CSCR in both eyes or CSCR may develop in the fellow eye during the trial. We propose to measure eye-specific outcomes such as BCVA in both eyes throughout the trial, designating eyes as study eyes or not. Statistical analyses will take into account the availability of data for two eligible eyes in one patient. If both eyes present with CSCR at baseline, the clinical trial site will decide which is the primary eye and this eye will have retinal imaging performed first. The primary eye would usually be the one with most active disease/most subretinal fluid. It will be identified by OCT imaging and subsequent investigations such as fluorescein and indocyanine green angiography will then be performed

Exclusion Criteria

Exclusion criteria as of 12/01/2017:
1. Hyperkalaemia (serum potassium level > 5.0 mmol/L)
2. Hepatic or renal impairment (Patients with severe renal insufficiency (Estimated glomerular filtration rate, eGFR <30 mL per minute per 1.73 m2) or Patients with severe hepatic insufficiency (Child-Pugh Class C)
3. Pregnancy or breast feeding
4. Known allergy to fluorescein or indocyanine green
5. Patients receiving potassium-sparing diuretics, potassium-supplements, or inhibitors of CYP 3A4 (e.g.amiodarone, diltiazem, fluconazole, itraconazole, ketoconazole, ritonavir, nelfinavir, saquinavir clarithromycin, telithromycin, erythromycin, verapamil, spironolactone and nefazodone)). Patients taking furosemide are eligible.
6. Patients receiving the combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB)
7. Patients receiving high doses of aspirin (>75mg)
8. Patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g. ibuprofen, naproxen).
9. Patients receiving lithium, cyclosporine or tacrolimus.
10. Hypersensitivity or known allergy to eplerenone or to any of the excipients.
11. Known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

The following additional exclusions apply to a study eye only (i.e. they may be present for a non-study eye):
1. Evidence of choroidal neovascularization
2. Previous or current treatment with eplerenone for any reason or previous or current treatment with photodynamic laser therapy / any anti-VEGF therapy in the study eye / any intra-ocular steroid use / thermal laser therapy for CSCR
3. Presence of any other disease which could cause retinal fluid or SRF to accumulate (e.g. diabetic retinopathy, polypoidal choroidal vasculopathy, domed shaped maculopathy or choroidal haemangioma) or affect visual acuity
4. Myopia > -6 dioptres

Original exclusion criteria:
1. Hyperkalaemia (serum potassium level > 5.0 mmol/L)
2. Concomitant use of potassium-sparing diuretics or potassium supplements
3. Hepatic or renal impairment (Patients with severe renal insufficiency (Estimated glomerular filtration rate, eGFR <30 mL per minute per 1.73 m2) or Patients with severe hepatic insufficiency (Child-Pugh Class C)
4. Pregnancy or breast feeding
5. Known allergy to fluorescein or indocyanine green
6. Patients receiving potassium-sparing diuretics, potassium-supplements or strong inhibitors of CYP 3A4 (e.g. itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone))
7. Patients receiving the combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB) with eplerenone

The following additional exclusions apply to a study eye only (i.e. they may be present for a non-study eye):
8. Evidence of choroidal neovascularization
9. Previous treatment with photodynamic laser therapy / any anti-VEGF therapy in the study eye / any intra-ocular steroid use / previous thermal laser therapy for CSCR
10. Presence of any other disease which could cause retinal or SRF to accumulate e.g. diabetic retinopathy, polypoidal choroidal vasculopathy, domed shaped maculopathy or choroidal hemangioma
11. Myopia > -6 dioptres

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary outcome as of 23/01/2017:<br>Best Corrected Visual Acuity measured using validated ETDRS vision charts, at the 12 month visit, adjusted for baseline BCVA.<br><br>Original primary outcome:<br>The change in Best Corrected Visual Acuity measured using validated ETDRS vision testing at baseline, 4 weeks, 3, 6, 9 and 12 months.