Prospective Randomized Controlled Treatment Trial for Chronic Central Serous Chorioretinopathy (PLACE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Radboud University
Sponsor:
Collaborators:
University of Cologne
University of Oxford
Leiden University Medical Center
University Hospital, Paris
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01797861
First received: February 21, 2013
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Chronic Central Serous Chorioretinopathy
Procedure: Half-dose photodynamic therapy (PDT)
Procedure: Micropulse laser (ML) treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Randomized Controlled Multicentre Trial Comparing Half-dose Photodynamic Therapy (PDT) With High-density Subthreshold Micropulse Laser Treatment in Patients With Chronic Central Serous Chorioretinopathy (CSC)

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Absence of subretinal fluid on OCT scan [ Time Frame: 6-8 weeks after treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Best-corrected visual acuity [ Time Frame: 6-8 weeks and 7-8 months after Treatment Visit 1 ] [ Designated as safety issue: No ]

    As secondary endpoints, we will mainly look at three parameters that reflect the patient's vision-related functioning. These three parameters are: a standardized measurement of best-corrected visual acuity (BCVA) according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) standards, a standardized measurement of sensitivity of the macula with microperimetry, and standardized assessment of the patient's vision-related quality of life using a validated questionnaire, the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25).

    The secondary endpoint with regard to BCVA that will be assessed as a reflection of functional improvement after treatment includes:

    • Mean change from baseline in ETDRS BCVA in the study eye at 6-8 weeks after Treatment Visit 1 and at 7-8 months after Treatment Visit 1
    • Mean change from Evaluation Visit 1 in ETDRS BCVA in the study eye at final evaluation (7-8 months after Treatment Visit 1)


Other Outcome Measures:
  • Macular sensitivity on microperimetry [ Time Frame: 6-8 weeks and 7-8 months after Treatment Visit 1 ] [ Designated as safety issue: No ]

    As secondary endpoints, we will mainly look at three parameters that reflect the patient's vision-related functioning. These three parameters are: a standardized measurement of best-corrected visual acuity (BCVA) according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) standards, a standardized measurement of sensitivity of the macula with microperimetry, and standardized assessment of the patient's vision-related quality of life using a validated questionnaire, the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25).

    The secondary endpoint with regard to macular sensitivity that will be assessed as a reflection of functional improvement after treatment includes:

    - Mean change from baseline in retinal sensitivity on microperimetry in the study eye at 6-8 weeks after Treatment Visit 1 and at 7-8 months after Treatment Visit 1 among the two treatment modalities


  • Vision-related quality of life as reported on the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) [ Time Frame: 6-8 weeks and 7-8 months after Treatment Visit 1 ] [ Designated as safety issue: No ]

    As secondary endpoints, we will mainly look at three parameters that reflect the patient's vision-related functioning. These three parameters are: a standardized measurement of best-corrected visual acuity (BCVA) according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) standards, a standardized measurement of sensitivity of the macula with microperimetry, and standardized assessment of the patient's vision-related quality of life using a validated questionnaire, the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25).

    The secondary endpoint with regard to vision-related quality of life that will be assessed as a reflection of functional improvement after treatment includes:

    - Mean change from baseline in the NEI VFQ-25 questionnaire at 6-8 weeks after Treatment Visit 1 and at 7-8 months after Treatment Visit 1 among the two treatment modalities


  • Number of second treatments [ Time Frame: 7-8 months after Treatment Visit 1 ] [ Designated as safety issue: No ]
    Another secondary endpoint concerns the number patients in each treatment arm who required a second treatment in an attempt to achieve an absence of subretinal fluid under the retina on OCT at 7-8 months after Treatment Visit 1


Estimated Enrollment: 140
Study Start Date: December 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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 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)
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.
Active Comparator: Micropulse laser (ML) treatment

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

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.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • male and female patients ≥ 18 years of age who are able to give written informed consent
  • active chronic central serous chorioretinopathy
  • decline in best-corrected visual acuity/BCVA (< 20/20 Snellen equivalent) associated with 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

Exclusion Criteria:

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01797861

Contacts
Contact: Camiel JF Boon, MD PhD FEBO 0031644185921 C.J.F.Boon@lumc.nl
Contact: Myrte Breukink, MD 0031243614448 myrte.breukink@radboudumc.nl

Locations
France
Creteil University Eye Clinic Not yet recruiting
Paris, France, 94010
Contact: Giuseppe Querques, MD PhD    0033145175230    giuseppe.querques@hotmail.it   
Contact: Eric Souied, MD PhD    0033145175230    eric.souied@chicreteil.fr   
Principal Investigator: Giuseppe Querques, MD PhD         
Sub-Investigator: Eric Souied, MD PhD         
Germany
Cologne University Eye Clinic Recruiting
Cologne, Germany, 50937
Contact: Sacha Fauser, MD PhD    00492214784105    sfauser@gmx.net   
Principal Investigator: Sacha Fauser, MD PhD         
Netherlands
Leiden University Medical Center Recruiting
Leiden, Netherlands
Contact: Camiel JF Boon, MD, PhD, FEBOphth       C.J.F.Boon@lumc.nl   
Contact: Greetje Dijkman, MD       G.Dijkman@lumc.nl   
Principal Investigator: Camiel JF Boon, MD, PhD, FEBOphth         
Sub-Investigator: Greetje Dijkman, MD         
Radboud University Nijmegen Medical Centre, Institute of Ophthalmology Recruiting
Nijmegen, Netherlands, 6500 HB
Contact: Myrte Breukink, MD    0031243614448    m.breukink@ohk.umcn.nl   
Contact: Camiel JF Boon, MD PhD FEBO    00447963061509    cjfboon@hotmail.com   
Principal Investigator: Carel B Hoyng, MD PhD         
Sub-Investigator: Myrte Breukink, MD         
Sub-Investigator: Jan Keunen, MD PhD FEBO         
United Kingdom
Oxford University Eye Hospital, John Radcliffe Hospital Not yet recruiting
Oxford, United Kingdom, OX3 9DU
Contact: Susan Downes, MD FRCOphth    00441865231122    Susan.Downes@ouh.nhs.uk   
Principal Investigator: Susan M Downes, MD FRCOphth         
Principal Investigator: Robert E MacLaren, PhD FRCO         
Sub-Investigator: Victor Chong, MD FRCOphth         
Sponsors and Collaborators
Radboud University
University of Cologne
University of Oxford
Leiden University Medical Center
University Hospital, Paris
Investigators
Study Chair: Camiel JF Boon, MD PhD FEBO Leiden University Medical Center & Radboud University Nijmegen Medical Center
Principal Investigator: Carel B Hoyng, MD PhD Radboud University
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 Oxford University
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01797861     History of Changes
Other Study ID Numbers: PLACE
Study First Received: February 21, 2013
Last Updated: March 3, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Medical Ethics Review Committee (METC)
Germany: Ethics Commission
United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: National Consultative Ethics Committee for Health and Life Sciences

Keywords provided by Radboud University:
chronic central serous chorioretinopathy
photodynamic therapy
micropulse laser

Additional relevant MeSH terms:
Central Serous Chorioretinopathy
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on July 23, 2014