Clinical trial NCT03079141: Photodynamic Therapy Versus Eplerenone: Treatment Trial for Chronic Central Serous Chorioretinopathy
Official title: Study on Half-dose Photodynamic Therapy Versus Eplerenone in Chronic CenTRAl Serous Chorioretinopathy (SPECTRA Trial)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Central Serous Chorioretinopathy
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Radboud University Medical Center
First posted: 2017-03-14
Enrollment: 107
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Absence of subretinal fluid on OCT scan
timeFrame: 3 months after (start) of treatment
Secondary outcomes:
measure: Macular sensitivity on microperimetry
timeFrame: At evaluation visits during study, depending on the effect of treatment. All patients will visit the outpatient clinic at 3 months, at 1 year, and at 2 years after the (start of) treatment.
measure: Mean change in best-corrected visual acuity
timeFrame: At evaluation visits during study, depending on the effect of treatment. All patients will visit the outpatient clinic at 3 months, at 1 year, and at 2 years after the (start of) treatment.
measure: Vision-related quality of life as reported on the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25)
timeFrame: At evaluation visits during study, depending on the effect of treatment. All patients will visit the outpatient clinic at 3 months, at 1 year, and at 2 years after the (start of) treatment.
measure: Number of cross-over treatments needed in each treatment arm
timeFrame: During study. At the evaluation visit at 3 months after the (start of) treatment, a possible cross-over treatment can be performed.
measure: The long-term outcome both after successful treatment and after non-successful treatment
timeFrame: One year and two year after (start of) therapy
measure: The number of (S)AEs in the 2 different treatment groups.
timeFrame: At the several evaluation visits within the study, at 3 months, at 1 year, and at 2 years after (the start of) treatment
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: Camiel JF Boon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: