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Atorvastatin in Acute Stroke Treatment

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ClinicalTrials.gov Identifier: NCT02225834
Recruitment Status : Completed
First Posted : August 26, 2014
Last Update Posted : August 26, 2014
Sponsor:
Information provided by (Responsible Party):
Antonino Tuttolomondo, University of Palermo

Brief Summary:

Recent clinical trials and meta-analyses of b-hydroxy-bmethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated a significant reduction in ischemic stroke in patients with a history of coronary artery disease, both with and without elevations of serum cholesterol. Recent data suggest that statins have other beneficial properties in addition to the retardation of atherosclerosis. Asahi et al demonstred that Statins increased eNOS and tPA mRNA levels but did not change mRNA levels of PAI-1 and that In eNOS knockout mice, atorvastatin reduced the volume of ischemic tissue and improved neurologic outcomes after arterial occlusion by blood clot emboli. In addition to their lipid-lowering effects, it has been speculated that statins may also have beneficial effects on cerebral circulation and brain parenchyma during ischaemic stroke and reperfusion. Aslanyan et al reported that statin use was associated with reduced mortality at 1 month during the follow-up.

In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke period .

Recently the investigators group reported that lacunar strokes compared to nonlacunar ones exhibited significantly lower plasma levels of TNF-α and IL1-β, P-selectin and ICAM-1 24-72 h and 7-10 days after stroke onset (4). At extracranial arterial territories, inflammation plays a crucial role mediating all the stages of the atherosclerosis process . Similarly, thrombosis and defective fibrinolysis may also contribute to the progression of atherosclerotic lesions . Interestingly, both mechanisms might have a relevant role in the pathogenesis of intracranial large artery atherosclerosis and ischemic stroke Moreover our group showed that Patients with cardioembolic and atherothrombotic stroke subtypes showed significantly higher median plasma levels of TNF-α, IL-6, IL-1β whereas the lacunar subtype showed significantly lower median plasma levels of TNF-α, IL-6 and IL-1β and that immunoinflammatory marker plasma levels are significantly related to ischemic lesion volume.

A meta-analysis showed that statins may possess antithrombotic property because these drugs were reported to reduce periprocedural infarction in patients undergoing percutaneous coronary intervention .

This clinical benefit was detected after median, 0.5 days of treatment with statins (indicating that statins could potentially exert an antithrombotic effect even earlier than supposed from pharmacological studies.

Violi et al recently showed the first evidence that atorvastatin acutely and simultaneously decreases oxidative stress and platelet activation by directly inhibiting platelet Nox2 and ultimately platelet isoprostanes and thromboxane A2 so providinf a rationale for the use of statins to prevent or modulate coronary thrombosis.

Whereas recent data suggest that inflammatory reactions are involved in the pathogenesis and progression of cerebral ischaemia , no study has evaluated effects of atorvastatin 80 mg/day after a recent stroke on stroke outcome and on immunoinflammatory markers so to evaluate acute antithrombotic and anti-inflammatory effects of atorvastatin also in acute cerebrovascular event setting.

On this basis the primary objective of the study was to evaluate the separate effects of atorvastatin in vivo on immunoinflammatory markers and on stroke prognosis in patients with recent acute ischemic stroke classified as atherothrombotic.


Condition or disease Intervention/treatment Phase
Ischemic Stroke Drug: Atorvastatin Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Early Atorvastatin Treatment During the Acute Phase of Stroke on Immunoinflammatory Markers and Outcome in Patients With Acute Ischemic Stroke Classified as LAAS According TOAST Classification
Study Start Date : November 2011
Actual Primary Completion Date : January 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: early Atorvastatin treatment
Ischemic stroke patients treated with with atorvastatin 80 mg at admission until discharge
Drug: Atorvastatin
treatment with atorvastatin 80 mg (once-daily) from admission day until discharge

No Intervention: no early treatment with atorvastatin
Ischemic stroke patients not treated with with atorvastatin 80 mg until discharge



Primary Outcome Measures :
  1. NIHSS score at 72 hour [ Time Frame: 72 hours ]
    differences with regard of NIHSS score at 72 hours

  2. differences in msRankin score [ Time Frame: 72 hours ]

Secondary Outcome Measures :
  1. Plasma levels of inflammatory cytokines at 72 hours [ Time Frame: 72 hours ]
    differences with regard of plasma levels of TNF-alfa, IL-1 beta, IL-6, E-Selectin, P-Selectin, ICAM-1, V-CAM1, VWF

  2. Outcome measure ( rankin score) [ Time Frame: seven days ]
    differences in msRankin score at seven day after admission



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligible patients were men and women over 18 years of age who had an acute ischemic stroke with a symptom time onset < 48 hours

Exclusion Criteria:

  • Patients with inflammatory or infectious diseases, cancer, hematological diseases and severe renal or liver failure, as well as those who were under treatment with anti-inflammatory were excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02225834


Locations
Italy
Internal Medicine Ward, University of Palermo
Palermo, Italy, 90127
Sponsors and Collaborators
University of Palermo

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Antonino Tuttolomondo, Assistant Professor, University of Palermo
ClinicalTrials.gov Identifier: NCT02225834     History of Changes
Other Study ID Numbers: 21770
First Posted: August 26, 2014    Key Record Dates
Last Update Posted: August 26, 2014
Last Verified: August 2014

Keywords provided by Antonino Tuttolomondo, University of Palermo:
Atorvastatin, ischemic stroke, cytokines

Additional relevant MeSH terms:
Stroke
Ischemia
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Atorvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors