Prospective Randomized Controlled Treatment Trial for Chronic Central Serous Chorioretinopathy

NCT01797861 | Completed Phase 4 DMC

• 1 other identifier: PLACE
• Study Type: interventional
• Target: 140
• Locations: 4 countries
• Sites: 5

Brief Summary

Chronic central serous chorioretinopathy (CSC) is a relatively frequent eye disease that often occurs in patients in the professionally active age range. In this disease, there is pooling of fluid under the central retina (the macula). This specific form of macular degeneration can cause permanent vision loss, image distortion, loss of color and contrast vision due to this fluid under the retina. 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 chronic CSC. Many retrospective studies suggest that treatment with photodynamic therapy (PDT) is effective in chronic CSC. Micropulse laser (ML) therapy may also be effective in this disease. The proposed study is the first prospective randomized controlled trial in chronic CSC. In this study, participants with chronic CSC will be randomized into two treatment groups, PDT or ML treatment. The trial is a superiority study, because retrospective studies suggest that PDT treatment may be more effective than ML treatment. Therefore, PDT treatment is challenged against ML treatment. The null hypothesis of the study is that PDT treatment is more effective than ML treatment in patients with active chronic CSC. The alternative hypothesis is that PDT treatment is not more effective than ML treatment in these patients. Treatment success will not only be based on anatomical improvement, but also on functional endpoints, which are most important from a patient's perspective. The study will take place in five large tertiary referral university hospitals in Europe that have extensive experience with conducting clinical trials (in Nijmegen, the Netherlands; Cologne, Germany; Leiden, the Netherlands; Oxford, United Kingdom; and Paris, France). Each of these centers has confirmed sufficient funding to conduct the research. The study will last max. 8 months per participant. Each participant will come for 5 (in the case of 1 treatment) or 7 visits (in the case of 2 treatments). Study evaluations will be mostly part of regular clinical care. The whole study will last for max. 24 months.

Conditions

Chronic Central Serous Chorioretinopathy

Keywords

chronic central serous chorioretinopathy; photodynamic therapy; micropulse laser

Outcome Measures

Primary Outcomes (1)

• Absence of subretinal fluid on OCT scan

  The primary endpoint of this study is to assess if there is a difference between the efficacy of half-dose photodynamic therapy treatment versus micropulse laser treatment in patients with chronic central serous chorioretinopathy. The assessment of this efficacy will be based on the anatomical effect on optical coherence tomography (OCT): absence of subretinal fluid versus persistent subretinal fluid, 6-8 weeks after treatment. After all, the absence or presence of fluid under the retina on the OCT scan is a direct reflection of the activity of the disease in these patients.

  6-8 weeks after treatment

Secondary Outcomes (1)

• Best-corrected visual acuity

  6-8 weeks and 7-8 months after Treatment Visit 1

Other Outcomes (3)

• Macular sensitivity on microperimetry

  6-8 weeks and 7-8 months after Treatment Visit 1

• Vision-related quality of life as reported on the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25)

  6-8 weeks and 7-8 months after Treatment Visit 1

• Number of second treatments

  7-8 months after Treatment Visit 1

Study Arms (2)

Half-dose photodynamic therapy (PDT)

ACTIVE COMPARATOR

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 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. If there still is subretinal fluid on OCT scan at Evaluation Visit 1 (6-8 weeks after Treatment Visit 1 / the first treatment with half-dose PDT), a second treatment with half-dose PDT will be performed (Treatment Visit 2).

Procedure: Half-dose photodynamic therapy (PDT)

Micropulse laser (ML) treatment

ACTIVE COMPARATOR

ML treatment with an 810 nm diode laser will be performed of the areas identified on mid-phase ICG angiography. Multiple laser spots will be applied, covering the leakage area on mid-phase ICG angiography. The area(s) that has to be treated is determined based on those hyperfluorescent area(s) on mid-phase (approximately 10 minutes) ICG-angiography that correspond to subretinal fluid accumulation in the macula on the OCT scan and hyperfluorescent "hot spots" on the mid-phase (3 minutes) fluorescein angiogram. If there still is subretinal fluid on OCT scan at Evaluation Visit 1 (6-8 weeks after Treatment Visit 1 / the first ML treatment), a second ML treatment will be performed (Treatment Visit 2).

Procedure: Micropulse laser (ML) treatment

Interventions

Half-dose photodynamic therapy (PDT) PROCEDURE

At exactly 15 minutes after the start of the half-dose verteporfin infusion, the PDT treatment will take place. The area that has to be treated with the PDT laser is determined based on those hyperfluorescent area(s) on mid-phase (approximately 10 minutes) ICG-angiography that correspond to subretinal fluid accumulation in the macula on the OCT scan and hyperfluorescent "hot spots" on the mid-phase (approximately 3 minutes) fluorescein angiogram. The spot size will be defined based on diameter of the hyperfluorescent area on ICG angiography plus 1mm. The treatment is performed with standard fluency (50 J/cm2), a PDT laser wavelength of 689 nm, and a standard treatment duration of 83 seconds.

Half-dose photodynamic therapy (PDT)

Micropulse laser (ML) treatment PROCEDURE

The following ML treatment settings will be used: a power of 1800 mW\*, a duty cycle of 5%, frequency of 500 Hz, exposure time of 0.2 s per spot, spot size: 125 µm, minimal distance of spot from fovea: 500 µm. \* Subthreshold treatment is desired, meaning that no visible reaction due to laser treatment has to be seen in the retina. In virtually all patients, a power of 1800 mW wil not produce a visible discoloration of the retina after application of a laser spot with the aforementioned settings. If retinal discoloration is seen at a power of 1800 mW the power will be reduced with steps of 300 mW until there is no visible reaction. The first laser "test" spot will always be applied just outside the macular area.

Micropulse laser (ML) treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male and female patients ≥ 18 years of age who are able to give written informed consent
• active chronic central serous chorioretinopathy
• subjective visual loss \> 6 weeks, interpreted as onset of active disease
• subretinal fluid that includes the fovea on OCT scanning at Baseline Examination.
• Please NOTE: Subretinal fluid does not have to include fovea on OCT to be eligible for treatment at Control Visit 1, as long as there is persistent subretinal fluid in the macula, which is interpreted as persistently active disease (see 5.7 "Retreatment criteria and considerations").
• hyperfluorescent areas on ICG angiography
• ≥1 ill-defined hyperfluorescent leakage areas on fluorescein angiography with retinal pigment epithelial window defect(s) that are compatible with chronic CSC

You may not qualify if:

• The participant may not enter the study if ANY of the following apply:
• any previous treatments for active CSC in the study eye
• current treatment with corticosteroids (topical or systemic), or anticipated start of corticosteroid treatment within the first 7-8 months from the start of the trial period
• evidence of other diagnosis that can explain serous subretinal fluid or visual loss
• BCVA \< 20/200 (Snellen equivalent)
• profound chorioretinal atrophy in central macular area on ophthalmoscopy and OCT
• myopia \> 6 dioptres
• 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 ICG angiography
• intraretinal edema on OCT
• (relative) contraindications for PDT 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 eligibility screening
• (relative) contraindications for fluorescein angiography or ICG angiography (known allergies especially against shellfish, previous reactions)
• Soft drusen in treated eye or fellow eye, signs of choroidal neovascularization on ophthalmoscopy and/or fluorescein angiography/indocyanine green angiography

Sponsors & Collaborators

• Radboud University Medical Center: lead
• University of Cologne: collaborator
• University of Oxford: collaborator
• Leiden University Medical Center: collaborator
• University Hospital, Paris: collaborator

Study Sites (5)

Creteil University Eye Clinic

Paris, 94010, France

Location

Cologne University Eye Clinic

Cologne, 50937, Germany

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Radboud University Nijmegen Medical Centre, Institute of Ophthalmology

Nijmegen, 6500 HB, Netherlands

Location

Oxford University Eye Hospital, John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (6)

• Feenstra HMA, Hahn LC, van Rijssen TJ, Tsonaka R, Breukink MB, Keunen JEE, Peters PJH, Dijkman G, Souied EH, MacLaren RE, Querques G, Downes SM, Fauser S, Hoyng CB, van Dijk EHC, Boon CJF. EFFICACY OF HALF-DOSE PHOTODYNAMIC THERAPY VERSUS HIGH-DENSITY SUBTHRESHOLD MICROPULSE LASER FOR TREATING PIGMENT EPITHELIAL DETACHMENTS IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY. Retina. 2022 Apr 1;42(4):721-729. doi: 10.1097/IAE.0000000000003363.

  PMID: 34864802 DERIVED

• Pfau M, van Dijk EHC, van Rijssen TJ, Schmitz-Valckenberg S, Holz FG, Fleckenstein M, Boon CJF. Estimation of current and post-treatment retinal function in chronic central serous chorioretinopathy using artificial intelligence. Sci Rep. 2021 Oct 14;11(1):20446. doi: 10.1038/s41598-021-99977-4.

  PMID: 34650220 DERIVED

• van Rijssen TJ, Hahn LC, van Dijk EHC, Tsonaka R, Scholz P, Breukink MB, Blanco-Garavito R, Souied EH, Keunen JEE, MacLaren RE, Querques G, Fauser S, Downes SM, Hoyng CB, Boon CJF. RESPONSE OF CHOROIDAL ABNORMALITIES TO PHOTODYNAMIC THERAPY VERSUS MICROPULSE LASER IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY: Place Trial Report No. 4. Retina. 2021 Oct 1;41(10):2122-2131. doi: 10.1097/IAE.0000000000003157.

  PMID: 34543244 DERIVED

• van Dijk EHC, Fauser S, Breukink MB, Blanco-Garavito R, Groenewoud JMM, Keunen JEE, Peters PJH, Dijkman G, Souied EH, MacLaren RE, Querques G, Downes SM, Hoyng CB, Boon CJF. Half-Dose Photodynamic Therapy versus High-Density Subthreshold Micropulse Laser Treatment in Patients with Chronic Central Serous Chorioretinopathy: The PLACE Trial. Ophthalmology. 2018 Oct;125(10):1547-1555. doi: 10.1016/j.ophtha.2018.04.021. Epub 2018 Jun 14.

  PMID: 29776672 DERIVED

• Breukink MB, Mohr JK, Ossewaarde-van Norel A, den Hollander AI, Keunen JE, Hoyng CB, Boon CJ. Half-dose photodynamic therapy followed by diode micropulse laser therapy as treatment for chronic central serous chorioretinopathy: evaluation of a prospective treatment protocol. Acta Ophthalmol. 2016 Mar;94(2):187-97. doi: 10.1111/aos.12938. Epub 2015 Dec 15.

  PMID: 26670630 DERIVED

• Breukink MB, Downes SM, Querques G, van Dijk EHC, den Hollander AI, Blanco-Garavito R, Keunen JEE, Souied EH, MacLaren RE, Hoyng CB, Fauser S, Boon CJF. Comparing half-dose photodynamic therapy with high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy (the PLACE trial): study protocol for a randomized controlled trial. Trials. 2015 Sep 21;16:419. doi: 10.1186/s13063-015-0939-z.

  PMID: 26390920 DERIVED

MeSH Terms

Interventions

Therapeutics

Study Officials

• Camiel JF Boon, MD PhD FEBO

  Leiden University Medical Center & Radboud University Nijmegen Medical Center

  STUDY CHAIR

• Carel B Hoyng, MD PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Sacha Fauser, MD PhD

  Cologne University Eye Clinic

  PRINCIPAL INVESTIGATOR

• Giuseppe Querques, MD PhD

  Creteil University Eye Clinic, Paris

  PRINCIPAL INVESTIGATOR

• Susan M Downes, MD FRCOphth

  Oxford Eye Hospital

  PRINCIPAL INVESTIGATOR

• Robert E MacLaren, PhD FRCO

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2013
• First Posted: February 25, 2013
• Study Start: December 1, 2013
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: October 10, 2017

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); NL (2); GB (1); DE (1)