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The first results of Anti-Vascular Endothelial Growth Factor (VEGF) therapy were very promising and superior to established therapies. Three different substances (all of them applied intravitreally) are available, but comparative studies have not yet been conducted. In this pilot study, the safety (number of adverse events) and efficacy (distance acuity testing retinal thickness measurement) of Avastin and Macugen applied as monotherapy will be compared to a combined treatment of Avastin followed by Macugen used for retreatment.
At least equal results of the combined therapy are expected.
The role of Vascular Endothelial Growth Factor (VEGF) in the pathogenesis of neovascular diseases like choroidal neovascularization (CNV) and proliferative diabetic retinopathy has been demonstrated in a series of publications. Therefore intravitreally applied VEGF antagonists have been used in the treatment of CNV in age-related macular degeneration (AMD) and diabetic cases. Three anti-VEGFs are available: Macugen® (Pegaptanib), Avastin® (Bevacizumab) and Lucentis® (Ranibizmab). Pegaptanib sodium is an aptamer designed to bind the VEGF 165 isoform with high affinity. Bevacizumab is a humanized monoclonal antibody to VEGF designed for intravenous administration and approved for the treatment of colorectal cancer. Ranibizumab is an anti-body binding site fragment that is derived from the same anti-VEGF antibody as bevacizumab. The decrease of retinal thickness measured in the OCT provides information concerning the amount of intraretinal fluid accumulation and therefore for the activity of a neovascular lesion. It has been proven that the aqueous humor levels of VEGF of eyes with CNV are significantly higher than those of eyes without ocular or systemic diseases. The retinal thickness and the VEGF concentration in the aqueous humor should give a good correlation to the anti vasogenic effect of the intravitreal treatment. In this study bevacizumab and pegaptanib as monotherapy should be compared with a combined therapy of bevacizumab applied first with pegaptanib used for retreatment. The benefit of this combined therapy should be that an initial blockage of all VEGF isoforms is necessary whereas for retreatment the blockage of the most important isoform in the pathogenesis of CNV is sufficient and the normal function of the retinal pigment epithelium and the choriocapillaris is not affected.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Avastin first followed by retreatment of Macugen |
|
| 2 | Active Comparator | Avastin intravitreally every 6 weeks |
|
| 3 | Active Comparator | Macugen intravitreally every 6 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| intravitreal injection of Bevacizumab (Avastin) | Drug | 1.25 mg Avastin intravitreally applied once in arm 1 every 6 weeks in arm 2 |
|
| Measure | Description | Time Frame |
|---|---|---|
| retinal thickness | 54 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| distance acuity | 54 weeks | |
| number of adverse events | 54 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ilse Krebs, MD | Ludwig Boltzmann Institute for Biomicroscopic Lasersurgery | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ludwig Boltzmann Institute for Retinology and Biomicroscopic Lasersurgery | Vienna | State of Vienna | A1030 | Austria |
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| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| ID | Term |
|---|---|
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| C495058 | pegaptanib |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Pegaptanib (Macugen) | Drug | 0.3 mg intravitreally applied every 6 weeks as long as required |
|
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |