Ranibizumab and the Risk of Arterial Thromboembolic Events (RATE)
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|ClinicalTrials.gov Identifier: NCT01319188|
Recruitment Status : Terminated (The study was terminated under the political pressure of the Federal Security Service of the Russian Federation (FSB) and the Russian Society of Cardiology)
First Posted : March 21, 2011
Last Update Posted : May 19, 2015
|Condition or disease||Intervention/treatment||Phase|
|Age-related Macular Degeneration Coronary Artery Disease Cerebrovascular Disorders||Drug: 0.5 mg of ranibizumab Procedure: 0.5 mg of ranibizumab + photodynamic therapy Other: Sham injection||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||380 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Care Provider)|
|Official Title:||Ranibizumab for Age-Related Macular Degeneration and the Risk of Arterial Thromboembolic Events (RATE)|
|Study Start Date :||June 2010|
|Actual Primary Completion Date :||October 2012|
|Actual Study Completion Date :||April 2015|
|Active Comparator: 0.5 mg of ranibizumab||
Drug: 0.5 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).
Other Name: Lucentis
|Active Comparator: injection + photodynamic therapy||
Procedure: 0.5 mg of ranibizumab + photodynamic therapy
Photodynamic treatment with ranibizumab for predominantly classic type neovascular age related macular degeneration.
Other Name: Lucentis + laser therapy
|Sham Comparator: Sham injection||
Other: Sham injection
Sham treatment for occult or minimally classic type neovascular age related macular degeneration.
Other Name: Sham comparator
- Arterial thromboembolic events rate [ Time Frame: at month 6, 12 and 24 ]
This is a combined primary outcome that included:
- all cause mortality
- nonfatal stroke
- nonfatal myocardial infarction
- vascular death
- Serum concentration of ranibizumab [ Time Frame: at month 6, 12 and 24 ]Serum concentration of ranibizumab
- Serum VEGF [ Time Frame: at month 6, 12 and 24 ]Measurement of serum VEGF
- Mean change in visual acuity (letters) [ Time Frame: at month 6, 12 an 24 ]mean change in visual acuity (letters)
- Coronary and/or cerebral stenting, and/or CABG rate [ Time Frame: at month 6, 12 an 24 ]Coronary and/or cerebral stenting, and/or CABG rate
- Total cholesterol [ Time Frame: at month 6, 12 and 24 ]Total cholesterol measurement
- Systolic blood pressure [ Time Frame: at month 6, 12 and 24 ]Systolic blood pressure
- NYHA (New York Heart Association) functional class of heart failure [ Time Frame: at month 6, 12 and 24 ]NYHA (New York Heart Association) functional class of heart failure
- Diabetes mellitus morbidity [ Time Frame: at month 6, 12 and 24 ]Diabetes mellitus morbidity
- Serum fibrinogen [ Time Frame: at month 6, 12 and 24 ]Serum fibrinogen measurements
- Serum C-RP [ Time Frame: at month 6, 12 and 24 ]Serum C-RP measurements
- Serum D-dimer [ Time Frame: at month 6, 12 and 24 ]Serum D-dimer measurements
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01319188
|De Haar Research Foundation|
|Rotterdam, South Holland, Netherlands, 3071PR|
|Ural Institute of Cardiology|
|Yekaterinburg, Russian Federation, 620144|
|Study Chair:||Jan Gabinsky, M.D., Ph.D.||Ural Institute of Cardiology|
|Study Director:||Alexander Kharlamov, M.D., Ph.D.||Ural Medical University|
|Principal Investigator:||Olga Kovtun, M.D., Ph.D.||Ural Medical University|