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

This study has been completed.
Sponsor:
Collaborator:
Anthera Pharmaceuticals
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00533039
First received: September 19, 2007
Last updated: October 8, 2009
Last verified: June 2008
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Drug: Varespladib (A-002)
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: sPLA2 Inhibition to Decrease Enzyme Release After PCI (SPIDER-PCI) Trial

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • A secondary endpoint will be occurrence of any major adverse cardiac events (MACE). [ Time Frame: 30 days post-angioplasty ] [ Designated as safety issue: Yes ]
  • A secondary outcome will be serum sPLA2 activity. [ Time Frame: 5-7 days post-angioplasty ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 164
Study Start Date: October 2007
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control
Subjects take 2 tablets BID. Placebo tablets are identical to active medication.
Drug: placebo
250mg tablets BID 3-5 days pre-angioplasty and 5 days post-angioplasty.
Experimental: Varespladib (A-002)
Subjects take 250mg tablets BID beginning 3-5 days pre-angioplasty and for 5 days post-angioplasty.
Drug: Varespladib (A-002)
250mg tablets BID for 3-5 days pre-angioplasty and 5 days post-angioplasty.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00533039

Locations
Canada, Ontario
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
Anthera Pharmaceuticals
Investigators
Study Chair: Vladimir Dzavik, MD University Health Network, Toronto
  More Information

No publications provided by University Health Network, Toronto

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vladimir Dzavik, MD, University Health Network
ClinicalTrials.gov Identifier: NCT00533039     History of Changes
Other Study ID Numbers: SPIDER001, A Sub-study of SPIDER-PCI
Study First Received: September 19, 2007
Last Updated: October 8, 2009
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Vascular Diseases
Varespladib methyl
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phospholipase A2 Inhibitors

ClinicalTrials.gov processed this record on October 30, 2014