Macular Degeneration
Conditions
Keywords
Anti-VEGF therapy, photodynamic therapy, neovascularization
Brief summary
Single agent anti-VEGF therapies such as ranibizumab have shown great promise and have set the standard for visual outcomes in treating wet macular degeneration. However, they need to be administered frequently by intraocular injections with the attendant risk of endophthalmitis, lens damage, retinal detachment, and vitreous hemorrhage. The purpose of this trial is to see if using photodynamic therapy in combination with ranibizumab will decrease the number of treatments with ranibizumab.
Detailed description
A randomized, prospective, multicenter trial will compare two groups of patients with subfoveal choroidal neovascularization secondary to AMD. One group will receive 0.5 mg. ranibizumab intraocularly initially. This will be repeated monthly for 3 months total and then as needed over the period of one year. The other group will receive Reduced Fluence-PDT (25 Joules) followed by 0.5 mg. of ranibizumab intraocularly on the same day. The second group will receive the combination of ranibizumab and RF-PDT as needed over a period of one year. Re-treatment will be determined by the individual investigator based on visual acuity, retinal thickness as measured by optical coherence tomography (OCT), and fluorescein angiography. Visual acuity and OCT measurements will be performed by masked examiners.
Interventions
DRUGranibizumab
0.5 mg. given as an intraocular injection
DRUGverteporfin
Standard dosage of 6 mgs. / meter2 of body surface area given intravenously.
Sponsors
Novartis
Texas Retina Associates
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willingness to sign informed consent. 2. Age greater than 50. 3. Evidence of macular degeneration in the form of drusen in either eye. 4. Visual acuity of 20/25 to 20/800. 5. Subfoveal choroidal neovascularization. Both occult and classic subtypes will be allowed. If lesion is purely occult there has to be one of the following: 1. Recent loss of vision (5 letters on ETDRS or doubling of visual angle by snellen) 2. Documented enlargement of lesion on FA 3. Increase of 50 microns or more in the central subfield on OCT 4. New blood 6. Total active lesion must be less than 12 disc areas in size. -
Exclusion criteria
1. Myopia, ocular histoplasmosis, or other retinal pathology that could affect vision 2. Previous treatment of the enrolled eye for CNV 3. Intraocular surgery within 6 weeks of enrollment 4. Geographic atrophy, subretinal fibrosis, or pigment epithelial tear involving the fovea of the eligible eye 5. Known hypersensitivity to verteporfin 6. Medical condition that would preclude regular follow-up for one year. 7. Previous vitrectomy 8. Media opacities limiting visual acuity, retinal examination, or retinal imaging. 9. A lesion where \> 50% of the lesion is a pigment epithelial detachment. -
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Percentage of Patients With Less Than 15 Letters of ETDRS Visual Loss at 12 Months. | 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Retreatments Over One Year | 1 year | Number of days to retreatment outcome changed to frequency of retreatments at maintenance visits. |
| Number of Injections Over 12 Months | 1 year | Additional number of ranibizumab injections given in each group over the 12 months |
| Percentage of Subjects Gaining More Than 15 ETDRS Letters of Acuity | 1 year | — |
| Improvement in OCT (Optical Coherent Tomography) Foveal Thickness at 12 Months | 1 year | Improvement in OCT (Optical coherent tomography) foveal thickness at 12 months/Number of microns in foveal thickness measurement |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group I Group I will receive 0.5 mg. ranibizumab intraocularly initially. This will be repeated monthly for 3 months total and then as needed over the period of one year. | 30 |
| Group II Group II will receive Reduced Fluence-PDT (25 Joules) followed by 0.5 mg. of ranibizumab intraocularly on the same day. The second group will receive the combination of ranibizumab and RF-PDT as needed over a period of one year. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Group I | Group II | Total |
|---|---|---|---|
| Age, Continuous | 79.1 years STANDARD_DEVIATION 8.35 | 79.3 years STANDARD_DEVIATION 7.23 | 79.2 years STANDARD_DEVIATION 7.72 |
| Region of Enrollment United States | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 14 Participants | 18 Participants | 32 Participants |
| Sex: Female, Male Male | 16 Participants | 12 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
The Percentage of Patients With Less Than 15 Letters of ETDRS Visual Loss at 12 Months.
Time frame: 1 year
Population: Fifty-six participants completed the full 12 month study. Four subjects did not return for the 12 month visit. No patients terminated the study due to adverse events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I | The Percentage of Patients With Less Than 15 Letters of ETDRS Visual Loss at 12 Months. | 22 percentage of participants |
| Group II | The Percentage of Patients With Less Than 15 Letters of ETDRS Visual Loss at 12 Months. | 14 percentage of participants |
Secondary
Improvement in OCT (Optical Coherent Tomography) Foveal Thickness at 12 Months
Improvement in OCT (Optical coherent tomography) foveal thickness at 12 months/Number of microns in foveal thickness measurement
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I | Improvement in OCT (Optical Coherent Tomography) Foveal Thickness at 12 Months | 91.4 microns | Standard Deviation 12.8 |
| Group II | Improvement in OCT (Optical Coherent Tomography) Foveal Thickness at 12 Months | 104.1 microns | Standard Deviation 9 |
Secondary
Number of Injections Over 12 Months
Additional number of ranibizumab injections given in each group over the 12 months
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I | Number of Injections Over 12 Months | 6.8 injections | Standard Deviation 2.49 |
| Group II | Number of Injections Over 12 Months | 3.0 injections | Standard Deviation 2.43 |
Secondary
Percentage of Participants With Retreatments Over One Year
Number of days to retreatment outcome changed to frequency of retreatments at maintenance visits.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I | Percentage of Participants With Retreatments Over One Year | 33 % of subjects requiring additional injec |
| Group II | Percentage of Participants With Retreatments Over One Year | 21 % of subjects requiring additional injec |
Secondary
Percentage of Subjects Gaining More Than 15 ETDRS Letters of Acuity
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I | Percentage of Subjects Gaining More Than 15 ETDRS Letters of Acuity | 33 percentage |
| Group II | Percentage of Subjects Gaining More Than 15 ETDRS Letters of Acuity | 31 percentage |