sPLA2 Inhibition to Decrease Enzyme Release After PCI Trial

• Status: Completed
• Trial end date: 2009-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Health Network, Toronto
• Collaborator: Anthera Pharmaceuticals
• Treatments: Varespladib methyl

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.