Ranibizumab Versus Low-fluence Photodynamic Therapy in the Treatment of Chronic Central Serous Chorioretinopathy

• Sponsor: Jang Won Heo (Other)
• Overall Status: Completed
• CT.gov ID: NCT01325181
• Collaborator: Novartis Korea Ltd. (Industry)
• Enrollment: 34
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and safety of intravitreal ranibizumab injection versus low-fluence PDT in the treatment of chronic CSC.

Condition or Disease	Intervention/Treatment	Phase
Chronic Central Serous Chorioretinopathy	Drug: Verteporfin; Drug: ranibizumab	Phase 1/Phase 2

Detailed Description

Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neurosensory retina. The pathophysiology of CSC is not certain and various theories are proposed including impaired function of retinal pigment epithelium (RPE), choroidal ischemia and choroidal hyperpermeability leading to RPE damage. Acute CSC with monofocal or paucifocal changes of RPE usually shows spontaneous resolution and has a favorable visual outcome. Chronic CSC is characterized by multifocal or diffuse decompensation of RPE associated with persistent detachment of neurosensory retina. This might lead to cystoid macular degeneration, foveal atrophy and damage to the foveal photoreceptor layer, consequently resulting in irreversible significant visual loss. Photodynamic therapy (PDT) was proposed for the treatment of chronic CSC. Modified parameters of PDT such as shortening of the time of laser emission and reduction of a total light energy have been suggested to reduce the irreversible damages induced by conventional PDT. Recently, intravitreal injection of antibody to vascular endothelial growth factor(VEGF) was proposed as a new treatment option based on the effect of anti-permeability. Several reports demonstrated acceptable outcomes after intravitreal bevacizumab injection, one of anti-VEGF agent. But the clinical results with ranibizumab are not reported yet. The purpose of this study is to compare the efficacy and safety of intravitreal ranibizumab injection versus low-fluence PDT in the treatment of chronic CSC.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Study on the Efficacy and Safety of Intravitreal Ranibizumab Versus Low-fluence Photodynamic Therapy in the Treatment of Chronic Central Serous Chorioretinopathy
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Low-fluence PDT with Verteporfin Half the regular laser fluence PDT(Visudyne®; Novartis); a total light energy of 25J/cm2, a light dose rate of 300mW/cm2. If subretinal fluid was sustained after primary treatment, rescue treatment(ranibizumab injection) was considered	Drug: Verteporfin; a 6mg/m2 infusion of verteporfin(Visudyne; Novartis)over 10 minutes followed by laser delivery; Other Names: Visudyne
Active Comparator: Ranibizumab Consecutive Intravitreal injection of ranibizumab(Lucentis®, Novartis) 0.5mg/0.05ml for the first 3 months. If subretinal fluid was sustained after primary treatment, rescue treatment(low-fluence photodynamic therapy) was considered	Drug: ranibizumab; Consecutive intravitreal injection of ranibizumab(Lucentis®, Novartis) 0.5mg/0.05ml for the first 3 months; Other Names: Lucentis

Outcome Measures

Primary Outcome Measures

1. Number of Participants That Achieved Complete Resolution of Subretinal Fluid on OCT Without Rescue Treatment [12 months]

   number of participants who achieved complete resolution of subretinal fluid on OCT without rescue treatment until the end of the study

Secondary Outcome Measures

1. Change From Baseline in logMAR BCVA [12 months]

   the changes from baseline in logMAR BCVA throughout the follow-up period

2. Change From Baseline in Central Foveal Thickness on OCT [12 months]

   the change from baseline in central foveal thickness measured by OCT throughout the follow-up period

3. Number of Participants With Leakage on Fluorescein Angiography [12 months]

   number of participants who showed fluorescein leakage after primary or rescue treatment throughout the follow-up period

4. Change From Baseline in Choroidal Hyperpermeability on Indocyanine Green Angiography [12 months]

   change from baseline in the status of choroidal perfusion and hyperpermeability on indocyanine green angiography throughout the follow-up period

5. Number of Participants Who Underwent Rescue Treatment [12 months]

   number of participants who underwent rescue treatment: ranibizumab injections for the low-fluence PDT group and low-fluence PDT for the ranibizumab group

6. Number of Participants With Adverse Event [12 months]

   number of participants with adverse event throughout the follow-up period including procedure and drug-related adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. best-corrected visual acuity (BCVA) between 0.0 and 1.0 logarithm of the minimal angle of resolution (logMAR)

2. presence of subfoveal fluid persisting for 3 months or more on optical coherence tomography (OCT)

3. presence of leakage and multifocal/diffuse RPE decompensation on fluorescein angiography (FA)

4. choroidal vascular hyperpermeability and abnormal dilation of choroidal vasculature on indocyanine angiography (ICGA)

Exclusion Criteria:

1. previous treatment, such as laser photocoagulation, PDT, intravitreal injection of steroid or anti-VEGF agent

2. evidence of choroidal neovascularization

3. any other ocular diseases that could affect visual acuity

4. systemic steroid treatment in the previous 12 months

5. media opacity such as cataract that could interfere with adequate acquisition of OCT, FA and ICGA images

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	• Department of Ophthalmology, Seoul National University College of Medicine	Seoul	Gyeonggi-do	Korea, Republic of

Sponsors and Collaborators

• Jang Won Heo
• Novartis Korea Ltd.

Investigators

• Principal Investigator: Jang Won Heo, Professor, Seoul National University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jang Won Heo, Associate professor, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT01325181
• Other Study ID Numbers: NOV001
• First Posted: Mar 29, 2011
• Last Update Posted: May 27, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by Jang Won Heo, Associate professor, Seoul National University Hospital: Chronic central serous chorioretinopathy; Ranibizumab; Photodynamic therapy
• Additional relevant MeSH terms: Central Serous Chorioretinopathy; Ranibizumab; Verteporfin

Study Results

Participant Flow

Arm/Group Title	Low-fluence PDT	Ranibizumab
Arm/Group Description
Period Title: Overall Study
STARTED	18	16
COMPLETED	18	14
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Low-fluence PDT	Ranibizumab	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	18	16	34
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 100%	16 100%	34 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.4 (8.2)	48.9 (7.5)	50.8 (7.7)
Sex: Female, Male (Count of Participants)
Female	3 16.7%	3 18.8%	6 17.6%
Male	15 83.3%	13 81.3%	28 82.4%
Region of Enrollment (participants) [Number]
Korea, Republic of	18 100%	16 100%	34 100%

Outcome Measures

1. Secondary Outcome

Title	Change From Baseline in logMAR BCVA
Description	the changes from baseline in logMAR BCVA throughout the follow-up period
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

2. Primary Outcome

Title	Number of Participants That Achieved Complete Resolution of Subretinal Fluid on OCT Without Rescue Treatment
Description	number of participants who achieved complete resolution of subretinal fluid on OCT without rescue treatment until the end of the study
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All study eyes were analyzed using intention to treat principle and the last observation forward method

Arm/Group Title	Low-fluence PDT	Ranibizumab
Arm/Group Description
Measure Participants	18	16
Number [participants]	16 88.9%	2 12.5%

3. Secondary Outcome

Title	Change From Baseline in Central Foveal Thickness on OCT
Description	the change from baseline in central foveal thickness measured by OCT throughout the follow-up period
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Number of Participants With Leakage on Fluorescein Angiography
Description	number of participants who showed fluorescein leakage after primary or rescue treatment throughout the follow-up period
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Change From Baseline in Choroidal Hyperpermeability on Indocyanine Green Angiography
Description	change from baseline in the status of choroidal perfusion and hyperpermeability on indocyanine green angiography throughout the follow-up period
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Number of Participants Who Underwent Rescue Treatment
Description	number of participants who underwent rescue treatment: ranibizumab injections for the low-fluence PDT group and low-fluence PDT for the ranibizumab group
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Number of Participants With Adverse Event
Description	number of participants with adverse event throughout the follow-up period including procedure and drug-related adverse events
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Low-fluence PDT		Ranibizumab
Arm/Group Description
All Cause Mortality
	Low-fluence PDT		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Low-fluence PDT		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Low-fluence PDT		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.