Condition category
Eye Diseases
Date applied
04/05/2016
Date assigned
06/05/2016
Last edited
19/01/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Central serous chorio-retinopathy (CSCR) is a poorly understood eye disease involving the retina. The retina is a layer of light-sensitive cells at the back of the eye which are responsible for converting light into electrical signals that are carried to the brain, where they are interpreted as the images we see. In CSCR, fluid (which leaks from a layer of tissue underneath the retina called the choroid) builds up under the retina causing vision to become distorted and leading to vision loss in around a third of cases. The exact cause of CSCR is unknown however there does appear to be a genetic link, as it often appears in members of the same family. Currently, there are no proven effective treatments. Recently a few patients have responded to treatment with a drug called eplerenone, which removes the fluid buildup and improves vision. However, information on the long term benefit and safety of this drug is lacking. The aim of this study is to test the effectiveness of eplerenone in the treatment of CSCR.

Who can participate?
Adults with visual impairment due to central serous chorio-retinopathy (CSCR)

What does the study involve?
Participants are randomly allocated to be treated with either a capsule containing eplerenone or a placebo capsule containing no active ingredients. For patients in the eplerenone group, a dosage of 25mg per day is given, which can be increased to 50mg after one week if tolerated. Participants attend study visits at four weeks and then three, six, nine and twelve months. At each visit, participants undergo sight tests, an eye examination, completing a number of questionnaires, as well as having blood samples taken. Participants are also asked for permission to take an additional blood sample at their first visit, so that the genetic material and other components from their blood can be stored for a future study. If the CSCR has resolved at any of these visits, the treatment is stopped (it can be restarted if it reoccurs).

What are the possible benefits and risks of participating?
There is no guarantee that the treatment used in this study will help individual participants, however the information from the results could help patients in the future. There are side effects associated with eplerenone usage but these will be managed through regular patient and safety data monitoring. There is also a small risk of pain or bruising during and after blood tests.

Where is the study run from?
Nineteen hospitals in England and Ireland (UK)

When is the study starting and how long is it expected to run for?
January 2016 to March 2019

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Dr Lucy Culliford
lucy.culliford@bristol.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Miss Lucy Ellis

ORCID ID

http://orcid.org/0000-0001-8179-5172

Contact details

CTEU Bristol
Level 7 Queens Building
Bristol Royal Infirmary
Marlborough Street
Bristol
BS2 8HW
United Kingdom
+44 117 342 3398
pslae@bristol.ac.uk

Additional identifiers

EudraCT number

2016-000113-70

ClinicalTrials.gov number

Protocol/serial number

20848

Study information

Scientific title

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

Acronym

VICI

Study hypothesis

The aim of the study is to compare the efficacy and safety of eplerenone with usual care versus placebo with usual care in the treatment of chronic Central serous chorio-retinopathy (CSCR).

Ethics approval

Wales Research Ethics Committee 1, 30/04/2016, ref: 16/WA/0069

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Ophthalmology, Primary sub-specialty: Glaucoma; UKCRC code/ Disease: Eye/ Disorders of choroid and retina

Intervention

Patients who consent will be randomised using an online system to active drug (Eplerenone) or placebo. They will be given a 25mg dose (tablet form) for 1 week, reviewed and if tolerated the dose will be increased to 50mg. They will be reviewed again at 4 weeks and then every 3 months for a year. Their vision will be assessed using visual acuity (letter charts) and specialised ophthalmic imaging, as well as quality of life questionnaires at the start and the end of the study. Treatment will be stopped at week 4, months 3, 6, 9 or 12 if there is complete resolution of sub-retinal fluid (SRF) under the fovea in the study eye. Treatment will be restarted at a subsequent visit if there is recurrence of sub-foveal SRF. The same dose escalation process will apply on restarting treatment. Treatment will be stopped for individual patients if they develop a complication of taking eplerenone. Also if at any of study visits visual acuity drops by 15 or more letters, the ophthalmologist may consider alternative therapies and may decide to stop the study intervention.

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

The change in Best Corrected Visual Acuity measured using validated ETDRS vision testing at baseline, 4 weeks, 3, 6, 9 and 12 months.

Secondary outcome measures

Secondary outcomes as of 12/01/2017:
1. Low luminance visual acuity is measured immediately after measuring BCVA at baseline, 4 weeks, 3, 6, 9 and 12 months by adding a 2 log neutral density filter and recording the number of letters read
2. Central subfield retinal thickness (CSRT) as measured by optical coherence tomography (OCT) estimated at 12 months, including CSRT measured at interim visits and adjusted for baseline CSRT
3. Change in sub-retinal fluid (SRF)thickness as measured by OCT at 12 months
4. Systemic and ocular adverse events at any time during the 12 month follow-up period
5. Proportion of patients with macular atrophy of the Retinal pigment epithelium (RPE) defined as hypoautofluorescence at 12 months
6. Area change in macular RPE hypoautofluorescence at 12 months
7. Choroidal thickness as measured by enhanced depth imaging OCT at 12 months, adjusted for baseline choroidal thickness
8. Proportion of patients with reduced choroidal permeability on Indocyanine green angiography at 12 months
9. Time to resolution of SRF as measured by OCT at 4 weeks, 3, 6, 9 and 12 months
10. Proportion of patients with complete resolution of SRF at each time point of the study
11. Patient-reported visual function using Visual Function Questionnaire VFQ 25 will be assessed at baseline and 12 months
12. Classification of all study eyes as complete, partial or no resolution of SRF at each time point of the study. Partial resolution of SRF is defined as a decrease of >25 % of CMT from baseline due to resolution of SRF. A non-responder is defined as having an increase in SRF or decrease in SRF ≤25% from baseline. Recurrence will be defined as the appearance of new SRF in a study eye after complete resolution of SRF at any point.
13. Classification of all study eyes by each FFA phenotype, such as smoke stack, ink-blot and chronic epitheliopathy, is assessed at baseline
14. Classification of all study eyes as early, late, or non responder. An early responder is defined as complete or partial resolution of sub-foveal SRF by 3 months. A late responder is defined as complete or partial resolution of sub-foveal SRF after 6 months
15. Incidence of CSCR in the fellow eye as measured by OCT, FFA, ICGA or AF at baseline, 4 weeks, 3, 6, 9 and 12 months

Original secondary outcomes:
1. Low luminance visual acuity is measured immediately after measuring BCVA at baseline, 4 weeks, 3, 6, 9 and 12 months by adding a 2 log neutral density filter and recording the number of letters read
2. Central subfield retinal thickness (CSRT) as measured by optical coherence tomography (OCT) estimated at 12 months, including CSRT measured at interim visits and adjusted for baseline CSRT
3. Change in sub-retinal fluid (SRF) volume as measured by OCT at 12 months
4. Systemic and ocular adverse events at any time during the 12 month follow-up period
5. Proportion of patients with macular atrophy of the Retinal pigment epithelium (RPE) defined as hypoautofluorescence at 12 months
6. Area change in macular RPE hypoautofluorescence at 12 months
7. Choroidal thickness as measured by enhanced depth imaging OCT at 12 months, adjusted for baseline choroidal thickness
8. Proportion of patients with reduced choroidal permeability on Indocyanine green angiography at 12 months
9. Time to resolution of SRF as measured by OCT at 4 weeks, 3, 6, 9 and 12 months
10. Proportion of patients with complete resolution of SRF at each time point of the study
11. Patient-reported visual function using Visual Function Questionnaire VFQ 25 will be assessed at baseline and 12 months
12. Correlation of final visual acuity (12 months) with age of patient
13. Correlation of presence of granular/confluent hypoautofluorescence in macula with final visual acuity at 12 months
14. Proportion of each Fundus Fluorescein angiogram phenotype such as smoke stack, ink-blot and chronic epitheliopathy at 12 months

Overall trial start date

01/01/2016

Overall trial end date

01/03/2019

Reason abandoned

Eligibility

Participant 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 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.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 104; UK Sample Size: 104

Participant 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

Recruitment start date

15/12/2016

Recruitment end date

30/09/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Victoria Hospital
274 Grosvenor Road
Belfast
BT12 6BA
United Kingdom

Trial participating centre

Royal Blackburn Hospital
Haslingden Road
Blackburn
BB2 3HH
United Kingdom

Trial participating centre

Bradford Royal Infirmary
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Bristol Eye Hospital
Lower Maudlin Street
Bristol
BS1 2LX
United Kingdom

Trial participating centre

Walsgrave General Hospital
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Frimley Park Hospital
Portsmouth Road Frimley
Camberly
GU16 7UJ
United Kingdom

Trial participating centre

Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Moorfields Eye Hospital
162 City Road
London
EC1V 2PD
United Kingdom

Trial participating centre

Manchester Royal Eye Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Royal Victoria Hospital
Queen Victoria Road
Newcastle-Upon-Tyne
NE1 4LP
United Kingdom

Trial participating centre

Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Southend University Hospital
Prittlewell Chase
Westcliff On Sea
SS0 0RY
United Kingdom

Trial participating centre

Sunderland Eye Infirmary
Queen Alexandra Road
Sunderland
SR2 9HP
United Kingdom

Trial participating centre

Torbay Hospital
Lowes Bridge
Torquay
TQ2 7AA
United Kingdom

Trial participating centre

New Cross Hospital
Wolverhampton Road Heath Town
Wolverhampton West
WV10 0QP
United Kingdom

Trial participating centre

York Hosptial
Wigginton Road
York
YO31 8HE
United Kingdom

Trial participating centre

St. James' University Hosptial
Beckett Street
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

University Hospital Southampton NHS Foundation Trust

Sponsor details

SGH - Level E
Laboratory and Pathology Block
SCBR - MP 138
Southampton
SO16 6YD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned dissemination of study results via scientific journals, conference presentations and a study website.

Intention to publish date

31/12/2019

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

12/01/2017: The following changes have been made to the record: 1. The recruitment start date has been updated from 01/09/2016 to 15/12/2016 2. York Hospital and St. James' University Hospital have been added as trial participating centres 3. The inclusion and exclusion criteria have been updated 4. The secondary outcome measures have been updated.