Age-related Macular Degeneration, Cerebrovascular Disorders, Coronary Artery Disease
Conditions
Keywords
Age-related macular degeneration, ranibizumab, acute thromboembolic events, coronary artery disease, cerebrovascular disease
Brief summary
The investigators assume that ranibizumab might be dangerous in patients with history of coronary artery disease or cerebrovascular events. The main objective of study is to reveal contraindications for ranibizumab prescription in patients with history of coronary artery disease and cerebrovascular events. Moreover, an association between management with ranibizumab and ATE rate in healthy above 50 years old persons is a concern of great interest as well.
Detailed description
Age-related macular degeneration (AMD) is a degenerative condition affecting the macula or central area of the retina in elderly people. Early AMD is marked by the presence of soft drusen and/or retinal pigment abnormality (hyper- and hypopigmentation). Late AMD includes 2 forms, nonneovascular (dry) AMD and neovascular (wet) AMD. Despite new medical and surgical interventions, AMD remains a leading cause of vision loss in elderly people all over the world. Ranibizumab is one of the most effective approaches of AMD management. Ranibizumab - a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A (VEGF A) - has been evaluated for the treatment of AMD. Ranibizumab binds to the receptor binding site of active forms of VEGF-A. VEGF-A cause neovascularization and leakage in models of ocular angiogenesis and vascular occlusion, and is thought to contribute to the progression of neovascular AMD and macular edema following RVO. Prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation. There have been a number of studies that have examined a possible association between ranibizumab and arterial thromboembolic events (ATE). The ATE rate in the three controlled neovascular AMD studies during the first year was 1.9% (17 out of 874; 0.3-0.5 mg LUCENTIS) vs 1.1% (5 out of 441) in control arms (AMD-1, AMD-2). In the second year the ATE rate was 2.6% (1323 patients; Lucentis 879) vs Control 444 (p \< 0.05). The ATE rate in the two controlled RVO studies (RVO-1, RVO-2) during the first six months was 0.8% (789 patients; Lucentis 527 vs Sham 262). The investigators assume that ranibizumab can be rather dangerous in patients with history of coronary artery disease or cerebrovascular events. The main objective of study is to reveal contraindications for ranibizumab prescription in patients with history of coronary artery disease and cerebrovascular events. Moreover, an association between management with ranibizumab and ATE rate in healthy above 50 years old persons is a concern of great interest as well.
Interventions
DRUG0.5 mg of ranibizumab
Intravitreous ranibizumab (0.5 mg, injections at four week intervals for six months followed by further treatment at three month intervals with total duration of treatment until 24 months).
PROCEDURE0.5 mg of ranibizumab + photodynamic therapy
Photodynamic treatment with ranibizumab for predominantly classic type neovascular age related macular degeneration.
OTHERSham injection
Sham treatment for occult or minimally classic type neovascular age related macular degeneration.
Sponsors
Ural Institute of Cardiology
De Haar Research Foundation
Ural State Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
* age - 50 years old and older * male and female * age-related macular degeneration (AMD) * have a lesion in the study eye with a total size of less than 12 optic disc areas for minimally classic or occult lesions but no more than 5400 μm in greatest linear dimension for predominantly classic lesions * have best corrected visual acuity of 6/12 to approximately 6/96 (Snellen equivalent), assessed with the use of charts from the Early Treatment Diabetic Retinopathy Study (ETDRS) (70 to 25 ETDRS 1 m equivalent letter scores; patients initially view the charts at a starting distance of 4 m, the number of correctly read letters are given a correction factor with the final letter score being the equivalent of a patient reading it at 1m. A score of 55 letters approximates to 6/24 Snellen acuity) * have no permanent structural damage to the central fovea * have had no previous treatment for exudative age related macular degeneration * healthy subjects (no history of cardio- or cerebrovascular events), or history of coronary artery disease (cardiovascular events - myocardial infarction, unstable angina), or history of cerebrovascular events (brain ischemia, and/or stroke), but not in the preceding six months
Exclusion criteria
* history of cardiovascular events (myocardial infarction, unstable angina) or cerebrovascular events in the preceding six months * stenting, or any surgery in the preceding six months * other acute illnesses in the preceding three months * III-IV NYHA functional class of heart failure * mental and brain disorders * pregnancy * family hypercholesterolemia * blood disorders * malignant tumors * participation to any drug investigation during the previous three months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arterial thromboembolic events rate | at month 6, 12 and 24 | This is a combined primary outcome that included: * all cause mortality * nonfatal stroke * nonfatal myocardial infarction * vascular death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum VEGF | at month 6, 12 and 24 | Measurement of serum VEGF |
| Mean change in visual acuity (letters) | at month 6, 12 an 24 | mean change in visual acuity (letters) |
| Coronary and/or cerebral stenting, and/or CABG rate | at month 6, 12 an 24 | Coronary and/or cerebral stenting, and/or CABG rate |
| Total cholesterol | at month 6, 12 and 24 | Total cholesterol measurement |
| Systolic blood pressure | at month 6, 12 and 24 | Systolic blood pressure |
| Serum concentration of ranibizumab | at month 6, 12 and 24 | Serum concentration of ranibizumab |
| Diabetes mellitus morbidity | at month 6, 12 and 24 | Diabetes mellitus morbidity |
| Serum fibrinogen | at month 6, 12 and 24 | Serum fibrinogen measurements |
| Serum C-RP | at month 6, 12 and 24 | Serum C-RP measurements |
| Serum D-dimer | at month 6, 12 and 24 | Serum D-dimer measurements |
| NYHA (New York Heart Association) functional class of heart failure | at month 6, 12 and 24 | NYHA (New York Heart Association) functional class of heart failure |
Countries
Netherlands, Russia
Outcome results
None listed