Indocyanine Angiographic Changes of Choroidal Neovascularization by Ranibizumab

• Sponsor: Pusan National University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01810042
• Collaborator: Novartis (Industry)
• Enrollment: 49
• Locations: 2
• Arm: 1
• Duration (Months): 28.1
• Patients Per Site: 24.5
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Exudative age-related macular degeneration (ARMD) is complicated by choroidal neovascularization (CNV). Although anti-vascular endothelial growth factor treatment is the gold standard treatment, recurrence is the main limitation of the treatment. The changes of the CNV vascular structure is expected to provide information regarding recurrence. In the eyes that the vascular structure is clearly seen in indocyanine green angiography (ICGA), the vascular changes after ranibizumab injections will be investigated prospectively.

Condition or Disease	Intervention/Treatment	Phase
Exudative Age-related Macular Degeneration	Drug: ranibizumab	Phase 4

Detailed Description

For patients having exudative ARMD with CNV, whose vascular structures are clearly demonstrated in ICGA , ranibizumab is injected monthly three times, then pro re nata to 6 months. Vascular structures of CNV is investigated at baseline, 3 and 6 months using ICGA. Expected number of patients are 48 eyes from 4 centers, competitively.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Interventional Case Series, Effect of Lucentis on Indocyanine Angiographic Changes in Patients With Wet Age-related Macular Degeneration
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ranibizumab 0.5mg of ranibizumab is injected into the vitreous cavity monthly 3 times for the 3 months then pro-re-nata (PRN) for following 3 months.	Drug: ranibizumab; 0.5mg of ranibizumab is injected into the vitreous cavity through pars plana.; Other Names: intravitreal injection of ranibizumab (Lucentis, Novartis)

Outcome Measures

Primary Outcome Measures

1. Caliber of Choroidal New Vessel (CNV) [6 months]

   Caliber of the largest CNV is measured using a software of IVAN (developed by Wisconsin University) that measures a caliber of retinal vessels using a semi-automatic method. An indocyanine green angiography (ICGA) image showing the vascular structures of CNV was processed to invert black and white for the analysis. The image was loaded in the software, and the course of the arteriolar CNV was indicated manually. Then average thickness of the vascular segment was calculated.

Secondary Outcome Measures

1. Lesion Size of CNV [6 months]

   Lesion size of CNV is measured in fluorescein angiography using software, and find correlation with caliber of choroidal new vessels.

2. Visual Acuity in ETDRS Letters [6 months]

   Visual acuity was assessed using the ETDRS chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Higher scores represents better functioning.

3. Visual Acuity Changes [baseline and 6 months]

   Visual acuity is measured at baseline and 6 months using ETDRS chart. The changes was calculated by visual acuity at 6 months minus visual acuity at baseline. Positive values represent improvement of visual acuity, and negative values represent worsening of visual acuity at 6 months compared to baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. age >= 50

2. Visual acuity of the study eye is between 20/400 and 20/40, and the other eye is 20/400 or better

3. Area of choroidal new vessel (CNV) clearly visible in indocyanine green angiography (ICGA) is more then 1/2 disc area.

4. Area of CNV clearly visible in ICGA is more than half of the total CNV area.

Exclusion Criteria:

1. CNV caused by other than age-related macular degeneration. (polypoidal choroidal vascularization, retinal angiomatous proliferation, degenerative myopia etc)

2. Blocked fluorescence in ICGA is more than half of the total CNV area.

3. Disciform scar

4. Previous anti-vascular endothelial growth factor (VEGF) treatment within 3 months

5. Previous any treatment of photodynamic therapy or photocoagulation

6. Previous intraocular or periocular injection of steroid within 3 months

7. Previous intraocular surgery except cataract surgery

8. Vitreo-retinal interface disease on the macula

9. Presence of other diseases may affect visual acuity (uveitis, glaucoma, diabetic retinopathy, etc.)

10. Uncontrolled periocular or intraocular infection

11. History of hypersensitivity to ranibizumab treatment

12. Uncontrolled systemic diseases (hypertension, diabetes mellitus, etc.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pusan National University Hospital	Busan		Korea, Republic of	602-739
2	Haeundae Baik Hospital	Busan		Korea, Republic of	612-896

Sponsors and Collaborators

• Pusan National University Hospital
• Novartis

Investigators

• Principal Investigator: Ji Eun Lee, MH, PhD, Pusan National Universtiy Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1432-44.
• Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31.
• Spaide RF. Rationale for combination therapies for choroidal neovascularization. Am J Ophthalmol. 2006 Jan;141(1):149-56. Review.
• Wong TY, Knudtson MD, Klein R, Klein BE, Meuer SM, Hubbard LD. Computer-assisted measurement of retinal vessel diameters in the Beaver Dam Eye Study: methodology, correlation between eyes, and effect of refractive errors. Ophthalmology. 2004 Jun;111(6):1183-90.

• Responsible Party: Ji Eun Lee, Associate professor, Pusan National University Hospital
• ClinicalTrials.gov Identifier: NCT01810042
• Other Study ID Numbers: 임상20120178
• First Posted: Mar 13, 2013
• Last Update Posted: May 4, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Ji Eun Lee, Associate professor, Pusan National University Hospital: age-related macular degeneration; choroidal neovascularization; ranibizumab; indocyanine angiography
• Additional relevant MeSH terms: Macular Degeneration; Choroidal Neovascularization; Ranibizumab

Study Results

Participant Flow

Recruitment Details	Total 53 patients were screened and 49 patients were enrolled from Oct 2010 to Feb 2013 in Pusan National University Hospital and Inje Baik Haeundae Hospital.
Pre-assignment Detail	This study has a single arm, and there was no assignment process.

Arm/Group Title	Ranibizumab
Arm/Group Description	Ranibizumab is injected monthly 3 times then pro re nata (PRN) to 6 months. intravitreal injection of ranibizumab: 0.5mg of ranibizumab is injected into the vitreous cavity through pars plana.
Period Title: Overall Study
STARTED	49
COMPLETED	39
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Ranibizumab
Arm/Group Description	Ranibizumab is injected monthly 3 times then PRN to 6 months. intravitreal injection of ranibizumab: 0.5mg of ranibizumab is injected into the vitreous cavity through pars plana.
Overall Participants	31
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	69
Sex: Female, Male (Count of Participants)
Female	12 38.7%
Male	19 61.3%
Region of Enrollment (participants) [Number]
Korea, Republic of	31 100%
Median visual acuity (ETDRS) (ETDRS letter) [Median (Full Range) ]
Median (Full Range) [ETDRS letter]	46
Central subfield macular thickness (um) (micrometer) [Median (Full Range) ]
Median (Full Range) [micrometer]	317

Outcome Measures

1. Primary Outcome

Title	Caliber of Choroidal New Vessel (CNV)
Description	Caliber of the largest CNV is measured using a software of IVAN (developed by Wisconsin University) that measures a caliber of retinal vessels using a semi-automatic method. An indocyanine green angiography (ICGA) image showing the vascular structures of CNV was processed to invert black and white for the analysis. The image was loaded in the software, and the course of the arteriolar CNV was indicated manually. Then average thickness of the vascular segment was calculated.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Of 31 patients included in the baseline analysis, 7 patients had the thickest vessels under limitation of measurement.

Arm/Group Title	Ranibizumab
Arm/Group Description	Ranibizumab is injected monthly 3 times then PRN to 6 months. intravitreal injection of ranibizumab: 0.5mg of ranibizumab is injected into the vitreous cavity through pars plana.
Measure Participants	24
Mean (Full Range) [micrometer]	43.53

2. Secondary Outcome

Title	Lesion Size of CNV
Description	Lesion size of CNV is measured in fluorescein angiography using software, and find correlation with caliber of choroidal new vessels.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Among 39 patients who completed the study, 8 patients were excluded because of poor ICGA quality or presence of polypoidal choroidal vasculopathy.

Arm/Group Title	Ranibizumab
Arm/Group Description	Ranibizumab is injected monthly 3 times then PRN to 6 months. intravitreal injection of ranibizumab: 0.5mg of ranibizumab is injected into the vitreous cavity through pars plana.
Measure Participants	31
Mean (Full Range) [square milimeter]	3.03

3. Secondary Outcome

Title	Visual Acuity in ETDRS Letters
Description	Visual acuity was assessed using the ETDRS chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Higher scores represents better functioning.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Among 39 patients who completed the study, 8 patients were excluded because of poor ICGA quality or presence of polypoidal choroidal vasculopathy.

Arm/Group Title	Ranibizumab
Arm/Group Description	Ranibizumab is injected monthly 3 times then PRN to 6 months. intravitreal injection of ranibizumab: 0.5mg of ranibizumab is injected into the vitreous cavity through pars plana.
Measure Participants	31
Median (Full Range) [ETDRS letters]	69

4. Secondary Outcome

Title	Visual Acuity Changes
Description	Visual acuity is measured at baseline and 6 months using ETDRS chart. The changes was calculated by visual acuity at 6 months minus visual acuity at baseline. Positive values represent improvement of visual acuity, and negative values represent worsening of visual acuity at 6 months compared to baseline.
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

Among 39 patients who completed the study, 8 patients were excluded because of poor ICGA quality or presence of polypoidal choroidal vasculopathy.

Arm/Group Title	Ranibizumab
Arm/Group Description	Ranibizumab is injected monthly 3 times then PRN to 6 months. intravitreal injection of ranibizumab: 0.5mg of ranibizumab is injected into the vitreous cavity through pars plana.
Measure Participants	31
Median (Full Range) [ETDRS letters]	12.5

Adverse Events

Arm/Group Title	Ranibizumab
Arm/Group Description	Ranibizumab is injected monthly 3 times then PRN to 6 months. intravitreal injection of ranibizumab: 0.5mg of ranibizumab is injected into the vitreous cavity through pars plana.
All Cause Mortality
	Ranibizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ranibizumab
	Affected / at Risk (%)	# Events
Total	2/49 (4.1%)
Gastrointestinal disorders
Liver cirrhosis	1/49 (2%)	2
Nervous system disorders
Cerebral infarction	1/49 (2%)	1
Other (Not Including Serious) Adverse Events
	Ranibizumab
	Affected / at Risk (%)	# Events
Total	0/49 (0%)

Limitations/Caveats

Small number of cases, high rate of follow-up loss. Technical problem with measuring caliber of choroidal new vessels.

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.