sPLA2 Inhibition to Decrease Enzyme Release After PCI Trial (SPIDER-PCI)
As evidence accumulates that atherogenesis or Coronary Artery Disease (CAD) may not be simply a disorder of lipid metabolism, but an inflammatory disease, the focus of treatment has shifted. A-002 or Varespladib is an anti-inflammatory drug for treatment of chronic and acute diseases. It acts by inhibiting secretory phospholipase A2 (sPLA2 ) - one of a family of enzymes leading to inflammation - which may be important in: 1) the development of atherosclerosis and 2) the increase in occurence of cardiovascular events after angioplasty. Previous studies have demonstrated that sPLA2: 1) facilitates the pro-atherogenic effects of low-density (LDL or bad cholesterol) and 2) increased levels post-angioplasty correlate with an increased risk of events at followup contact. Therefore this study proposes to investigate the ability of A-002 to prevent or reduce myocardial damage after angioplasty by inhibiting the cascade of inflammatory mediators.
Substudy - Subjects who agree will also have a vascular ultrasound 24h post-PCI to assess endothelial function.
Coronary Artery Disease
Drug: Varespladib (A-002)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||sPLA2 Inhibition to Decrease Enzyme Release After PCI (SPIDER-PCI) Trial|
- The primary endpoint will be incidence of myocardial injury as evidenced by elevation of CK-MB or troponin I above the upper limit of normal. [ Time Frame: 8 hours and 18-24 hours post-angioplasty ] [ Designated as safety issue: Yes ]
- A secondary endpoint will be occurrence of elevation of CK-MB or troponin I above the upper limit of normal. [ Time Frame: 8 and 18-24 hours post-angioplasty ] [ Designated as safety issue: Yes ]
- A secondary endpoint will be occurrence of any major adverse cardiac events (MACE). [ Time Frame: 30 days post-angioplasty ] [ Designated as safety issue: Yes ]
- A secondary outcome will be serum sPLA2 activity. [ Time Frame: 5-7 days post-angioplasty ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2007|
|Study Completion Date:||June 2009|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
Placebo Comparator: Control
Subjects take 2 tablets BID. Placebo tablets are identical to active medication.
250mg tablets BID 3-5 days pre-angioplasty and 5 days post-angioplasty.
Experimental: Varespladib (A-002)
Subjects take 250mg tablets BID beginning 3-5 days pre-angioplasty and for 5 days post-angioplasty.
Drug: Varespladib (A-002)
250mg tablets BID for 3-5 days pre-angioplasty and 5 days post-angioplasty.
Tissue injury after angioplasty is likely due to micro-emboli from mechanical trauma to a thrombotic lesion during angioplasty. In response to the ischemia sPLA2, possibly localized within atherosclerotic vascular tissue as well as from macrophages and monocytes, is released. Following ischemia-induced release, sPLA2 can bind to ischemically challenged cardiomyocytes and adversely affect their survival either directly through toxic effects on cardiomyocytes or indirectly by facilitating inflammation. It may be possible through sPLA2 inhibition to salvage non-lethally jeopardized cells following an ischemic episode thereby reducing the infarcted area and amount of tissue damage. Previous studies in patients with unstable angina support this hypothesis, and conclude that sPLA2 levels can be used to predict clinical outcomes. We hypothesize that sPLA2 inhibition with A-002 will reduce myocardial injury post-angioplasty.
Substudy - Peripheral vascular ultrasound should be done prior to receiving study drug and 24h post-PCI. Coronary endothelial function will be assessed at the time of PCI.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00533039
|Toronto General Hospital|
|Toronto, Ontario, Canada, M5G 2C4|
|Study Chair:||Vladimir Dzavik, MD||University Health Network, Toronto|