Study on half-dose Photodynamic therapy versus Eplerenone in chronic CenTRAl serous chorioretinopathy (SPECTRA trial)

The proposed study is the first prospective randomized controlled trial that
compares half-dose PDT with eplerenone treatment in patients with chronic
central serous chorioretinopathy, with regard to their ability to achieve
complete resolution of SRF, and their ability to improve the quality of vision.
In this study, we have chosen half-dose PDT since it is considered to be the
standard treatment for cCSC in many centers worldwide. Eplerenone treatment has
been chosen as the treatment of choice in the control arm, because this
relatively new and non-invasive therapy for cCSC has been described to lead to
promising results, and to less AEs in comparison with the other
mineralocorticoid antagonist spironolactone. Eplerenone treatment for cCSC is
also used as standard first-line treatment in many centers worldwide. A
multicenter randomized controlled trial, in which half-dose PDT and
high-density micropulse laser treatment are included, is currently conducted
and led by our group.
In this study, we want to define treatment success not only on the basis of
structural parameters (absence of SRF on optical coherence tomography (OCT)
after treatment), but also based on functional vision-related endpoints, both
on the short-term and long-term. With the results of this study we hope to
establish a strong scientific foundation for further research on the optimal
treatment of patients with cCSC to improve the visual outcome and quality of
life of this relatively frequently occurring retinal disease.

Primary Objective: to investigate whether half-dose PDT treatment leads to a
higher percentage of cCSC patients with SRF on OCT at baseline, achieving an
absence of this SRF on OCT as compared to eplerenone treatment.
Secondary Objectives: to investigate the clinical outcome comparing half-dose
PDT treatment with eplerenone treatment in patients with SRF due to active
leakage in cCSC, based on evaluation of best-corrected visual acuity, retinal
sensitivity on microperimetry, and subjective scores on the National Eye
Institute Visual Function Questionnaire.

This study is a multicenter, prospective, randomized, and controlled,
open-label study that will compare the efficacy and safety of 2 treatments in
patients with cCSC. The first group of patients will receive half-dose PDT
treatment. The second group of patients will receive eplerenone treatment. Each
patient will receive at least 1 treatment, but may be eligible to receive a
cross-over treatment after the evaluation visit at 3 months after the
initiation of treatment, from either half-dose PDT to eplerenone, or from
eplerenone to half-dose PDT. Potentially eligible patients will be identified
from 3 ophthalmology trial sites in the Netherlands.
Multimodal imaging (fundus photographs, FA, ICGA, and OCT images) collected at
the Baseline Evaluation will be sent to a central reading center (CRC). The CRC
will review these images to confirm subject eligibility based on the
characteristics specified in the inclusion criteria. Once eligibility has been
confirmed by the CRC, all other inclusion and exclusion criteria have been met
at the Baseline Evaluation, and informed consent (IC) has been obtained,
patients will be enrolled in the trial.
There are 9 examinations that will be performed at the Baseline Evaluation, 3
months after the initiation of treatment (at Evaluation Visit 1), and 3 months
after the possible initiation of cross-over treatment (Evaluation Visit 2). The
necessity of the performance of FA and ICGA at Evaluation Visit 3 and at Final
Evaluation Visit will be according to the discretion of the treating
ophthalmologist. In principle, FA and ICGA images will be acquired when there
is persistent SRF on OCT at Evaluation Visit 3 and Final Evaluation Visit.
The 6 anatomical assessments include ophthalmoscopy, fundus photography, OCT
(including OCT angiography), autofluorescence imaging, FA, and ICGA. The 3
functional assessments include visual acuity measurement, microperimetry, and a
questionnaire on vision-related functioning.
Enrolled patients will be randomized at a 1:1 ratio to receive half-dose PDT
treatment or eplerenone treatment. When contra-indications for the prescription
of eplerenone will be detected after Baseline Evaluation, these patients will
receive half-dose PDT.

The total number of visits per patient for this trial is 5 (in case of 1
required treatment) or 7 (in case of 2 required treatments). The duration of
participant participation from the beginning until the end of study is 24
months.

In the half-dose 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 15 minutes after the
start of the infusion, PDT laser treatment is performed with standard 50 J/cm2
fluency, PDT laser wavelength of 689 nm, and treatment duration of 83 seconds.
For treatment with PDT in cCSC patients, the administration of verteporfin has
previously been considered not to be study medication.
In the eplerenone arm, patients will receive 25 mg eplerenone once daily for 1
week, and when no abnormalities will be detected in the serum potassium, 50 mg
eplerenone will be taken orally once daily until 3 months after initiation of
treatment.

The included patients in this study do not have to attend additional visits,
and no additional invasive procedures will be performed within this study. The
only additional procedure to be carried out by the included patients is the
answering of questionnaires.
Both treatments are currently prescribed to cCSC patients worldwide. One of the
possible outcomes of this randomized controlled trial is that a treatment could
be superior to the other, but a cross-over of treatment will be performed when
complete resolution of SRF does not occur at 3 months after the initiation of
treatment (Evaluation Visit 1).