Photodynamic Therapy Versus Eplerenone: Treatment Trial for Chronic Central Serous Chorioretinopathy

NCT ID: NCT03079141

Last Updated: 2019-10-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-20
• Study Completion Date: 2021-08-31

Brief Summary

Chronic central serous chorioretinopathy (cCSC) is a relatively frequently occurring eye disease that is often diagnosed in patients in the professionally active age range. In this disease, a subretinal fluid accumulation occurs, due to abnormalities in both the choroid and the retinal pigment epithelium. This specific form of macular degeneration can cause permanent vision loss, image distortion, and loss of color and contrast vision. An early diagnosis and treatment may improve the visual outcome and quality of life.

To date there is no international consensus on the optimal treatment of cCSC. Many retrospective studies suggest that treatment with photodynamic therapy (PDT) is effective in chronic CSC. Treatment with oral eplerenone may also be effective in this disease.

In this proposed prospective randomized controlled trial, cCSC patients will be randomized into one of both treatment groups: either half-dose PDT or oral eplerenone treatment. The trial is a superiority study, because retrospective studies suggest that PDT treatment may be more effective than eplerenone treatment.

The null hypothesis of the study is that PDT treatment is more effective than eplerenone treatment in patients with active cCSC. The alternative hypothesis is that PDT treatment is not superior to eplerenone treatment.

Treatment success will not only be based on characteristics on ophthalmological imaging, but also on functional endpoints (both on the outcome of questionnaires, best-corrected visual acuity, and microperimetry), which are most important from a patient's perspective.

The study will take place in 3 large tertiary referral university hospitals in The Netherlands that have extensive experience with conducting clinical trials (Academic Medical Center (Amsterdam, the Netherlands), Radboud University Medical Center (Nijmegen, the Netherlands), and Leiden University Medical Center (Leiden, the Netherlands). Both the Radboud University Medical Center and the Leiden University Medical Center have been involved in the first prospective randomized controlled trial that is currently conducted in cCSC.

This study will last 2 years per participant. Each participant will visit the outpatient clinic for a maximum number of 6 visits.

A total number of 107 patients will be included in the trial. Depending on the speed of inclusion of patients in this trial, the total duration of this study can be determined.

Detailed Description

Chronic central serous chorioretinopathy (cCSC) is a relatively frequently occurring eye disease that is often diagnosed in patients in the professionally active age range. In this disease, a subretinal fluid accumulation occurs, due to abnormalities in both the choroid and the retinal pigment epithelium. This specific form of macular degeneration can cause permanent vision loss, image distortion, and loss of color and contrast vision. An early diagnosis and treatment may improve the visual outcome and quality of life.

To date there is no international consensus on the optimal treatment of cCSC. Many retrospective studies suggest that treatment with photodynamic therapy (PDT) is effective in chronic CSC. Treatment with oral eplerenone may also be effective in this disease.

In this proposed prospective randomized controlled trial, cCSC patients will be randomized into one of both treatment groups: either half-dose PDT or oral eplerenone treatment. The trial is a superiority study, because retrospective studies suggest that PDT treatment may be more effective than eplerenone treatment.

The null hypothesis of the study is that PDT treatment is more effective than eplerenone treatment in patients with active cCSC. The alternative hypothesis is that PDT treatment is not superior to eplerenone treatment.

Treatment success will not only be based on characteristics on ophthalmological imaging, but also on functional endpoints (both on the outcome of questionnaires, best-corrected visual acuity, and microperimetry), which are most important from a patient's perspective.

The study will take place in 3 large tertiary referral university hospitals in The Netherlands that have extensive experience with conducting clinical trials (Academic Medical Center (Amsterdam, the Netherlands), Radboud University Medical Center (Nijmegen, the Netherlands), and Leiden University Medical Center (Leiden, the Netherlands). Both the Radboud University Medical Center and the Leiden University Medical Center have been involved in the first prospective randomized controlled trial that is currently conducted in cCSC.

This study will last 2 years per participant. Each participant will visit the outpatient clinic for a maximum number of 6 visits, depending on the outcome of treatment. Study evaluations will be mostly part of regular clinical care.

A total number of 107 patients will be included in the trial. Depending on the speed of inclusion of patients in this trial, the total duration of this study can be determined.

Conditions

Chronic Central Serous Chorioretinopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Half-dose photodynamic therapy (PDT)

In the PDT treatment arm, all patients will receive an intravenous drip through which half-dose (3 mg/m2) verteporfin (Visudyne®) is administered, with an infusion time of 10 minutes. At exactly 15 minutes after the start of the infusion, PDT laser treatment is performed with standard 50 J/cm2 fluency, a wavelength of 689 nm, and a treatment duration of 83 seconds.

When patients are randomized to the PDT arm of this study, they will receive this treatment as a first cCSC treatment. Moreover, PDT can be performed in patients in whom SRF is still present on OCT at the Evaluation Visit at 3 months after the start of eplerenone treatment.

Group Type: ACTIVE_COMPARATOR

Photodynamic therapy

Intervention Type: OTHER

In the PDT treatment arm, all patients will receive an intravenous drip through which half-dose (3 mg/m2) verteporfin (Visudyne®) is administered, with an infusion time of 10 minutes. At exactly 15 minutes after the start of the infusion, PDT laser treatment is performed with standard 50 J/cm2 fluency, a wavelength of 689 nm, and a treatment duration of 83 seconds.

When patients are randomized to the PDT arm of this study, they will receive this treatment as a first cCSC treatment. Moreover, PDT can be performed in patients in whom SRF is still present on OCT at the Evaluation Visit at 3 months after the start of eplerenone treatment.

Oral eplerenone treatment

Patients will receive 25 milligrams oral eplerenone once daily for a week, and - when no abnormalities during blood testing for potassium and renal clearance can be detected both before treatment and during the first week of treatment - will receive 50 milligrams oral eplerenone for another 11 weeks thereafter.

When patients are randomized to the eplerenone arm of this study, they will receive this treatment as a first cCSC treatment. Moreover, eplerenone treatment can be initiated in patients in whom SRF is still present on OCT at the Evaluation Visit at 3 months after PDT treatment.

Group Type: ACTIVE_COMPARATOR

Eplerenone

Intervention Type: DRUG

Patients will receive 25 milligrams oral eplerenone once daily for a week, and - when no abnormalities during blood testing for potassium and renal clearance can be detected both before treatment and during the first week of treatment - will receive 50 milligrams oral eplerenone for another 11 weeks thereafter.

When patients are randomized to the eplerenone arm of this study, they will receive this treatment as a first cCSC treatment. Moreover, eplerenone treatment can be initiated in patients in whom SRF is still present on OCT at the Evaluation Visit at 3 months after PDT treatment.

Interventions

Eplerenone

Patients will receive 25 milligrams oral eplerenone once daily for a week, and - when no abnormalities during blood testing for potassium and renal clearance can be detected both before treatment and during the first week of treatment - will receive 50 milligrams oral eplerenone for another 11 weeks thereafter.

When patients are randomized to the eplerenone arm of this study, they will receive this treatment as a first cCSC treatment. Moreover, eplerenone treatment can be initiated in patients in whom SRF is still present on OCT at the Evaluation Visit at 3 months after PDT treatment.

Intervention Type: DRUG

Photodynamic therapy

In the PDT treatment arm, all patients will receive an intravenous drip through which half-dose (3 mg/m2) verteporfin (Visudyne®) is administered, with an infusion time of 10 minutes. At exactly 15 minutes after the start of the infusion, PDT laser treatment is performed with standard 50 J/cm2 fluency, a wavelength of 689 nm, and a treatment duration of 83 seconds.

When patients are randomized to the PDT arm of this study, they will receive this treatment as a first cCSC treatment. Moreover, PDT can be performed in patients in whom SRF is still present on OCT at the Evaluation Visit at 3 months after the start of eplerenone treatment.

Intervention Type: OTHER

Other Intervention Names

Inspra

Eligibility Criteria

Inclusion Criteria

• Age of ≥ 18 years of age and able to give written informed consent;
• Active chronic central serous chorioretinopathy (cCSC);
• Subjective visual loss > 6 weeks, interpreted as onset of active disease;
• Foveal subretinal fluid (SRF), on optical coherence tomography (OCT), at Baseline Examination;
• ≥1 ill-defined hyperfluorescent leakage areas on fluorescein angiography (FA) with retinal pigment epithelial window defect(s) that are compatible with cCSC;
• Hyperfluorescent areas on indocyanine green angiography (ICGA).

Exclusion Criteria

• Any previous treatments for active CSC;
• Previous prescription of mineralocorticoid receptor antagonists, for cCSC or for other diseases;
• Current treatment with corticosteroids (topical or systemic), corticosteroid use within 3 months before possible start of trial treatment, or anticipated start of corticosteroid treatment within the first 2 years from the start of the trial period;
• Evidence of another diagnosis that can explain serous SRF or visual loss;
• Best-corrected visual acuity < 20/200 (Snellen equivalent);
• Profound chorioretinal atrophy in central macular area on ophthalmoscopy and OCT;
• Myopia > 6D;
• Visual loss and/or serous detachment on OCT < 6 weeks;
• Continuous and/or progressive visual loss > 18 months or serous detachment on OCT > 18 months;
• No hyperfluorescence on ICGA;
• Intraretinal edema on OCT;
• (relative) Contraindications for FA or ICGA;
• (relative) Contraindications for photodynamic treatment (pregnancy, porphyria, severely disturbed liver function). Pregnancy will not be routinely tested in female patients, but the possibility of pregnancy will be discussed during screening
• (relative) Known contraindications for initiation of eplerenone treatment (hyperkalemia, abnormal renal clearance, severe hepatic insufficiency (Child-Pugh C), type 2 diabetes mellitus with microalbuminuria, concomitant use of potassium supplements, potassium-sparing diuretics, strong CYP3A4 inhibitors, or the combination of an ACE-inhibitor and an angiotensin receptor blocking agent). Pregnancy will not be routinely tested in female patients, but the possibility of pregnancy will be discussed during screening;
• Soft drusen in treated eye or fellow eye, signs of choroidal neovascularization on ophthalmoscopy and/or FA/ICGA of the study eye.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

CJFBoon

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Camiel JF Boon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Academic Medical Center

Amsterdam, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Radboud University Medical Center

Nijmegen, , Netherlands

Countries

Netherlands

References

Feenstra HMA, Diederen RMH, Lamme MJCM, Tsonaka R, Fauser S, Yzer S, van Rijssen T, Gkika T, Downes SM, Schlingemann RO, Hoyng CB, van Dijk EHC, Boon CJF. INCREASING EVIDENCE FOR THE SAFETY OF FOVEA-INVOLVING HALF-DOSE PHOTODYNAMIC THERAPY FOR CHRONIC CENTRAL SEROUS CHORIORETINOPATHY. Retina. 2023 Mar 1;43(3):379-388. doi: 10.1097/IAE.0000000000003686. Epub 2023 Jan 2.

Reference Type: DERIVED

PMID: 36727801 (View on PubMed)

Other Identifiers

P16.255

Identifier Type: -

Identifier Source: org_study_id