Clinical trial NCT00533039: sPLA2 Inhibition to Decrease Enzyme Release After PCI Trial
Official title: sPLA2 Inhibition to Decrease Enzyme Release After PCI (SPIDER-PCI) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Disease
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Anthera Pharmaceuticals
First posted: 2007-09-21
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Men or women ≥ 18 years of age undergoing elective PCI, with or without stenting

Exclusion Criteria:

* ST elevation MI or any troponin elevation (non-STEMI) within preceding 10days
* Elevation of CK-MB or troponin I at baseline
* Recent (4 weeks) coronary bypass surgery
* NYHA class III-IV heart failure
* Left ventricular ejection fraction \< 0.30
* Severe valvular heart disease
* Chronic inflammatory disease (e.g., lupus, rheumatoid arthritis, inflammatory bowel disease), or patients receiving steroid drugs
* Presence of severe liver disease with cirrhosis
* Recent active hepatitis
* Active chronic hepatitis
* ALT or AST \> 3 × upper limit of normal (ULN)
* Biliary obstruction with hyperbilirubinemia (total bilirubin \> 2 × ULN)
* Moderate or severe renal impairment (creatinine \> 1.5 × ULN)
* Nephrotic syndrome or subjects undergoing dialysis
* Uncontrolled diabetes (HbA1c \> 11% 1 month prior to screening)
* Initiation of statin therapy within 30 days
* Inability to provide consent.

Primary outcomes:
measure: 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.
timeFrame: 8 hours and 18-24 hours post-angioplasty
Secondary outcomes:
measure: A secondary endpoint will be occurrence of elevation of CK-MB or troponin I above the upper limit of normal.
timeFrame: 8 and 18-24 hours post-angioplasty
measure: A secondary endpoint will be occurrence of any major adverse cardiac events (MACE).
timeFrame: 30 days post-angioplasty
measure: A secondary outcome will be serum sPLA2 activity.
timeFrame: 5-7 days post-angioplasty
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Vladimir Dzavik, MD
role: STUDY_CHAIR
References:
citation: Dzavik V, Lavi S, Thorpe K, Yip PM, Plante S, Ing D, Overgaard CB, Osten MD, Lan J, Robbins K, Miner SE, Horlick EM, Cantor WJ. The sPLA2 Inhibition to Decrease Enzyme Release after Percutaneous Coronary Intervention (SPIDER-PCI) trial. Circulation. 2010 Dec 7;122(23):2411-8. doi: 10.1161/CIRCULATIONAHA.110.950733. Epub 2010 Nov 22.