- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00533039
sPLA2 Inhibition to Decrease Enzyme Release After PCI Trial (SPIDER-PCI)
sPLA2 Inhibition to Decrease Enzyme Release After PCI (SPIDER-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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 2C4
- Toronto General Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Control
Subjects take 2 tablets BID.
Placebo tablets are identical to active medication.
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250mg tablets BID 3-5 days pre-angioplasty and 5 days post-angioplasty.
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Experimental: Varespladib (A-002)
Subjects take 250mg tablets BID beginning 3-5 days pre-angioplasty and for 5 days post-angioplasty.
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250mg tablets BID for 3-5 days pre-angioplasty and 5 days post-angioplasty.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
8 hours and 18-24 hours post-angioplasty
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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8 and 18-24 hours post-angioplasty
|
A secondary endpoint will be occurrence of any major adverse cardiac events (MACE).
Time Frame: 30 days post-angioplasty
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30 days post-angioplasty
|
A secondary outcome will be serum sPLA2 activity.
Time Frame: 5-7 days post-angioplasty
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5-7 days post-angioplasty
|
Collaborators and Investigators
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SPIDER001
- A Sub-study of SPIDER-PCI
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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