sPLA2 Inhibition to Decrease Enzyme Release After PCI Trial (SPIDER-PCI)

University Health Network, Toronto

Status and phase

Completed

Phase 2

Conditions

Coronary Artery Disease

Treatments

Drug: placebo

Drug: Varespladib (A-002)

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00533039

SPIDER001

A Sub-study of SPIDER-PCI

Details and patient eligibility

About

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.

Full 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.

Enrollment

164 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.