The Effects of Bindarit in Preventing Stent Restenosis
The main study objective is to assess the efficacy and safety of different bindarit dosages compared to placebo in preventing restenosis, in patients submitted to coronary stenting and using a bare metal stent (Vision BMS, by Abbott).
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Pilot Study to Evaluate the Efficacy and Safety of Different Bindarit Dosages in Preventing Stent Restenosis|
- in-segment late loss (in-stent and 5 mm proximally and distally to the stent) measured by QCA [ Time Frame: 6 months from the index procedure ] [ Designated as safety issue: No ]Late loss is defined as the difference between post-procedural minimum lumen diameter and 6-month minimum lumen diameter measured in-stent and in-segment.
- Major Adverse Cardiac Events (MACE) [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]MACE are defined as the occurrence of death, Myocardial Infarction (MI), target vessel revascularization and target lesion revascularization(CABG or PTCA).
- the assessment of the safety profile of the two bindarit dosages compared to placebo [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]Safety will be assessed by monitoring the frequency of adverse events in each treatment group. Changes from baseline in physical examination, vital signs, and ECG will be also assessed. Laboratory analyses will be evaluated on the basis of the normal range, the Investigator's judgement, and mean changes from baseline (when applicable).
- the imaging parameters evaluated with OCT as an optional procedure performed on a subgroup of patients. [ Time Frame: 6 months from the index procedure ] [ Designated as safety issue: No ]
The following parameters will be evaluated:
- the neointimal proliferation on the surface of the stent struts;
- the frequency of stent malapposition.
- the assessment of inflammatory biomarkers in order to investigate the bindarit mechanism of action. [ Time Frame: 9 months ] [ Designated as safety issue: No ]determination of the plasma levels of several circulating inflammatory biomarkers (i.e. MCP-1/CCL-2, MCP-3/CCL7) involved in the neointimal hyperplasia and tissue proliferation occurring in site or adjacent to the stent sites.
|Study Start Date:||January 2009|
|Study Completion Date:||April 2011|
|Primary Completion Date:||January 2011 (Final data collection date for primary outcome measure)|
|Experimental: bindarit 600 mg||
300 mg bid, that is one 300 mg tablet twice a day for 6 months;
|Experimental: bindarit 1200 mg||
600 mg bid, that is two 300 mg tablets twice a day for 6 months
|Placebo Comparator: placebo||
bindarit-matching placebo tablets for 6 months.
Coronary artery disease is caused by the gradual build-up of fatty deposits in coronary arteries (atherosclerosis). A diminished blood flow may cause chest pain (angina), shortness of breath or other symptoms. A complete blockage can cause a heart attack. Angioplasty and stenting techniques are safe and effective procedures performed to unblock coronary arteries. However, a recurrent problem after angioplasty is the occurrence of a new blockage, usually within 6 to 9 months after the initial procedure. This phenomenon, called "restenosis", is a body's response to the injury of the angioplasty and does not mean a progression of coronary artery disease.The pathophysiology of restenosis is complex and has as yet not been fully clarified.
Serial studies have shown that in-stent restenosis is almost exclusively caused by neointimal hyperplasia and tissue proliferation occurring in site or adjacent to the stent sites. Histological studies confirmed that neointimal hyperplasia post-stent implantation is related to vessel injury during the procedure. Chemokines have been implicated in the pathogenesis of vascular injury. In this context, MCP-1 which shows a potent chemotactic action on monocytes, can amplify the inflammatory response through the recruitment of additional monocytes. In addition, MCP-3 is known to share some key biological features with MCP-1. It has been proved that MCP-1 directly induces human vascular smooth muscle proliferation acting at this level as a potent mitogen, and that anti-MCP-1 gene therapy inhibits restenotic changes (neointimal hyperplasia) in animals after balloon injury.
An evidence of a critical increase in circulating MCP-1 after coronary angioplasty was reported. It was more evident and prolonged in patients with restenosis rather than in non-restenotic patients, in which only a transient increases in plasma MCP-1 has been demonstrated.
Since these chemokines showed to play a main role in the appearance and worsening of the restenosis process, a selective inhibitor of MCP-1 and other members of monocyte chemotactic protein subfamily of CC inflammatory chemokines (MCP-3/CCL7, MCP-2/CCL8), such as bindarit, may have a potential therapeutic use in preventing restenosis by inhibiting the VSMC proliferation, and without affecting the important process of re-endothelization.
|Fondazione S.Raffaele del Monte Tabor - UO Emodinamica e Cardiologia Interventistica|
|Milan, Italy, 20132|
|Study Chair:||Antonio Colombo, MD||Fondazione S.Raffaele del Monte Tabor - U.O Emodinamica e Cardiologia Interventistica|