Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT00496405 |
| Other study ID # |
APEC |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
April 2007 |
| Est. completion date |
October 2007 |
Study information
| Verified date |
June 2024 |
| Source |
Asociación para Evitar la Ceguera en México |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The endothelial growth factor (VEGF), has been implied in the genesis of diverse Neovascular
disease. In the industrialized and developing countries, the main cause of blindness is the
diabetic retinopathy. Bevacizumab (Avastin, genentech, Inc., San Francisco, California, the
USA) is a drug.In the last years its use "off-label", in ophthalmology field, has become
popular. This is due to its proven safeness and effectiveness for the treatment of diverse
ocular diseases. A lot has been speculated about the systemic absorption of Bevacizumab. It
is for that reason that the objective of this study is the systematic and random revision of
the fellows eyes, of the patients programmed for the intravitreal administration of
Bevacizumab, with bilateral macular edema. In such a way that the therapeutic value in the
fellow eye of bevacizumab can be determined
Description:
Introduction:
The endothelial growth factor (VEGF), was identified for the first time in the liquid of
ascitis in Guinean pigs (6,7). It is a dimeric glycoprotein, naturally expressed in
epithelial and tumor cells (1). It's over expression during retinal hypoxia (9), has been
implied in the genesis of diverse Neovascular diseases (2,4,8,9,19). The activation of the
VEGF pathway promotes endothelial cells growth, increases the growth, migration and survival
of the existing vasculature and produces the differentiation and migration of the endothelial
mother cells from the bone marrow towards the general circulation (4). It is also a
vasculature permeability factor, because it favors the formation of vascular fenestrations,
which produces the exit of liquid and protein deposit in the tissue interstice, favoring the
formation of macular edema and neovascularisation (3,8-10).
Its activity is mediated by two tyrosine related receptors of high affinity: the VEGFR 1
(FLT-1) and VEGFR 2 (FLT-2) (1,9). The FLT-1 promotes the cellular proliferation whereas the
FLT-2 the migration and the interaction between cells and extracellular matrix(4,5,10)
In the industrialized and developing countries, the main cause of blindness is the diabetic
retinopathy (9). Followed close in the United States and Europe by Age related Macular
Degeneration (10). The most frequent cause of loss of vision in diabetic retinopathy is
macular edema (7). Its incidence is between 13.9 to 25.4% (15). It is characterized by the
accumulation of intraretinal liquid at level of the outer plexiform and internal nuclear
layers, with the subsequent thickening of the macula (13,15). The diabetic macular Edema is
associated to high levels of VEGF in the vitreous (7,8,9). At the moment, the gold standard
in the treatment of the proliferative retinopathy is the laser photocoagulation(9). The
photocoagulation of the macular area for the treatment of diffuse or focal edema, produces a
50% decrease risk of severe visual loss. Nevertheless the long-term prognosis continues being
poor (15).
The Optical Coherent Tomography (OCT) is a relative new, noninvasive technique (12,14), based
in low frequency interferometry phenomenon. It is able to provide cross-sectional retinal
images (11,12,15,17). It has a resolution of 10-15mm. thanks to that, it is also able to
quantitatively measure macular thickness (10,12,14,15,17). The measurements obtained with
this system are highly reproducible and they correlated with patient visual acuity
(7,11,14,16,17,19). It is very useful when evaluating the vitreous-retinal interface and
retinal adherences(11). In the macular edema OCT displays low reflectivity images with
increase of retinal thickness(11,13). The classification of macular edema by OCT images,
proposed by Dr. Otani (16) and modified by Kang (15) consists of 4 types: Type 1, thickening
of the fovea with homogenous optical reflectivity in the entire retina. Type 2, thickening of
the retina with noticeable diminution of the optical reflectivity in the external layers of
the retina. Type 3, thickening of the fovea with accumulation of subfoveal liquid and a
defined border of detached retina. Type 3A without foveal traction, 3B with foveal traction
(15).
Bevacizumab (Avastin, genentech , Inc., San Francisco, California, the USA) is a drug,
approved by the FDA for the treatment of the metastatic colorectal cancer(2). It consists of
a humanized monoclonal antibody that binds all active forms of VEGF (3,18,19), blocking the
activity of its two receptors (4). In the last years its use "off-label", in ophthalmology
field, has become popular. This is due to its proven safeness and effectiveness for the
treatment of diverse ocular diseases (2-4,7,20). Within the ophthalmic pathologies that have
been treated successfully with the Intravitreal administration of Bevacizumab, we can mention
different Neovascular pathologies (diabetic Retinopathy (9,18), age related macular
degeneration(2,4,18)) and pathologies that alter the vascular permeability (macular edema
(4,7), Central and branch retinal vein occlusion (3,8,20), central serous choroidopathy). In
all of them , treatment responses is characterized by an improvement of the visual acuity,
decrease of macular thickness and improvement of the angiographic patterns (8,10). The
potential complications of the use of Bevacizumab are the severe thromboembolic event,
arterial hypertension (18), epistaxis, proteinuria,hemoptysis, alteration in wound healing
and gastrointestinal bleed (4,10).
Exposition of the Problem:
A lot has been speculated about the systemic absorption of Bevacizumab. In a study at the
Bascom Palmer Eye Institute, doctors Rosenfeld, Puliafito et al demonstrated the
effectiveness of the systemic application of Bevacizumab for the treatment of the age related
macular degeneration applying dose of 5mg/Kg. thus Demonstrating, the passage of the molecule
from the systemic circulation to specific tissue in both eyes(10). Recently, doctor Bakri and
her team at Mayo Clinic in Rochester, Minnesota, establish that a small portion of
intravitreal bevacizumab is able to pass to the systemic circulation (1.6% of the injected
dose) obtaining detectable concentrations in the vitreous of the fellow eye (11.17ng/ml) at
week number 4 after the treatment (21). In the same way, we have cases in our hospital,
reported like anecdotal cases, of Bevacizumab application in one eye and improvement of the
base pathology in the fellow eye.
It is for that reason that the objective of this study is the systematic and random revision
of the fellows eyes, of the patients programmed for the intravitreal administration of
Bevacizumab, with bilateral macular edema. In such a way that the therapeutic value of the
small concentrations reached in the vitreous of the fellow eye of bevacizumab can be
determined.
