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NCT Number: NCT00533039

sPLA2 Inhibition to Decrease Enzyme Release After PCI Trial

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.

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Key information

Conditions

Coronary Artery Disease Arterial Occlusive Diseases Arteriosclerosis Cardiovascular Diseases Coronary Disease Heart Diseases Myocardial Ischemia Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Varespladib (A-002)

Drug

250mg tablets BID for 3-5 days pre-angioplasty and 5 days post-angioplasty.

Placebo

Drug

250mg tablets BID 3-5 days pre-angioplasty and 5 days post-angioplasty.

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. A secondary endpoint will be occurrence of any major adverse cardiac events (MACE).

    Time frame: 30 days post-angioplasty

  3. A secondary outcome will be serum sPLA2 activity.

    Time frame: 5-7 days post-angioplasty

Sponsors and collaborators

Lead sponsor

University Health Network, Toronto

Other

Collaborators

  • Anthera Pharmaceuticals

Registry information

Official study title

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

Acronym: SPIDER-PCI

Important dates

Study start
2007
Primary completion
2009
Study completion
2009
First posted
Sep 21, 2007
Registry last updated
Oct 9, 2009

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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