Oxidative Stress and Oxysterols Profiling in Patients With Carotid Revascularization "ICAR"

Completed

Phase N/A Results N/A

Trial Description

The combination of aspirin and dipyridamole, two antiplatelet drugs, is approved in Italy for the secondary prevention of cerebral embolism in patients with carotid atherosclerosis.
Besides antiplatelet activity, Dipyridamole has additional pharmacological action, including vasodilation and antioxidant properties.
A role for oxidative stress has been suggested in acute cerebrovascular disease. In this study the investigators want to test the in vivo antioxidant activity of dipyridamole in patients who are candidate to take the drug under approved conditions of the Italian Drug Regulation Agency, i.e. secondary prevention of TIA/Stroke in patinets with carotid stenosis (>= 70%).
To test the hypothesis that dipyridamole acts as antioxidant in vivo, oxysterols (products of cholesterol autoxidation) and vitamin E are measured in plasma before and after 6 months therapy after carotid endoarterectomy. Since dipyridamole is approved as combination preparation with aspirin, a control group of patients taking aspirin alone is enrolled.
Outcome measures: plasma biomarkers (oxysterols and vitamin E) change at two time points: baseline and 6-months therapy.

Detailed Description

Dipyridamole has been shown to act as potent antioxidant in vitro. The aim of the present study is to analyze if dipyridamole retains the antioxidant in vivo in man.
The investigators identified a clinical setting where dipyridamole is approved for clinical use, i.e. secondary prevention of stroke, to test the hypothesis that dipyridamole given orally could affect circulating markers of oxidative stress, in particular reduction in oxysterols (autoxidation products of cholesterol) and increase in vitamin E concentration.
Methods. Two arms are included in the study: a) dipyridamole plus aspirin (in Italy the use of dipyridamole is approved in combination with aspirin); b) aspirin alone as comparison arm. Patients eligible for endoarterectomy for the presence of carotid stenosis >= 70% are randomized in the two arms. The study is open labeled for the patient and clinical investigators who have in charge the patinets . The study is blinded for the technicians performing biomarker assessment and investigators responsible for data analysis.
Blood is taken at baseline (before surgery) and after six months of treatment. Oxysterol profiling and vitamin E are measured by isotope dilution gas chromatography and mass spectrometry.

Conditions

Interventions

  • Aspirin Drug
    Intervention Desc: Aspirin is a standard and guidelines supported therapy for patients undergoing carotid endoarterectomy as secondary prevention measure of cardiovascular risk
    ARM 1: Kind: Experimental
    Label: aspirin
    Description: acetylsalcylic acid 100 mg per day give orally for six months, starting the day of carotid endoartherectomy
  • Aspirin plus dipyridamole Drug
    Other Names: aspirin 25 mg plus dipyridamole extended release 200 mg; aggrenox
    Intervention Desc: the combination of aspirin plus dipyridamole is approved to lower the risk of stroke in people who have had a transient ischemic attack or stroke
    ARM 1: Kind: Experimental
    Label: aspirin plus dipyridamole
    Description: acetylsalicylic acid 25 mg plus dipyridamole extended release 200 mg, combined in a capsule, per day starting the day of carotid endoartherectomy

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Investigator)
  • Endpoint: Bio-equivalence Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Level of oxysterol measured by isotope dilution gas chromatography-mass spectrometry 6-months No
Primary Level of alpha- and gamma-tocopherol (vitamin E isomers) by isotope dilution gas chromatography-mass spectrometry 6-months No

Sponsors