Acetaminophen in aSAH to Inhibit Lipid Peroxidation and Cerebral Vasospasm
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Status:
Ongoing. Enrolling by invitation.
Purpose:
To determine whether acetaminophen (APAP), N-acetylcysteine (NAC), and APAP in combination with NAC will inhibit lipid peroxidation in aneurysmal subarachnoid hemorrhage (aSAH), utilizing F2-IsoPs as biomarkers for lipid peroxidation.
Interventions:
Acetaminophen
Anti-pyretic analgesic; potent inhibitor of hemoprotein-catalyzed lipid peroxidatrion with an IC50 for hemoglovin of 15uM, which is in the range of plasma levels resulting from therapeutic doses of the drug in humans. It acts by reducing the ferryl-oxo radical form of the heme, and thereby prevents formation of the hemoprotein radical that initiates lipid peroxidation.
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N-acetylcysteine (IV)
Metabolite of the sulfur-containing amino acid, Cysteine. N-Acetyl Cysteine is produced within the human body. N-acetyl-Cysteine is the acetylated form of L-Cysteine. It is rapidly metabolized to intracellular glutathione. Has antioxidant properties. Will inhibit hemoprotein-catalyzed lipid peroxidation.
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N-acetylcysteine (oral)
Metabolite of the sulfur-containing amino acid, Cysteine. N-Acetyl Cysteine is produced within the human body. N-acetyl-Cysteine is the acetylated form of L-Cysteine. It is rapidly metabolized to intracellular glutathione. Has antioxidant properties. Will inhibit hemoprotein-catalyzed lipid peroxidation.
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Year Started:
2007
Design:
Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Safety/Efficacy Study, Interventional.
Inclusion Criteria
Fisher Grade III or III + IV SAH based upon admitting CT scan
Aneurysm secured by either clipping or coiling within 72 hours of SAH; intracranial aneurysm confirmed by angiography or CTA; presence of ventriculostomy for external ventricular drainage (EVD) prior to randomization.
Exclusion Criteria
Enrollment in another interventional study; patient is pregnant or lactating; known co-morbidities that could affect outcome of this study; contraindication to CTA; serum creatinine > 1.4; documented allergy to iodinated contrast that cannot be adequately treated with premedication; documented allergy and/or intolerance to ApAP; baseline liver disease; history of recent alcohol abuse with documented ALT or AST above normal laboratory values; documented history of both malnutrition and decreased serum albumin below normal lab values; documented abnormal platelet count below normal lab values; documented abnormal PT or PTT above normal lab values; history or evidence of active asthma; documented allergy and/or intolerance to N-acetylcysteine; currently taking phenytoin, carbamazepine, or phenobarbital; currently taking isoniazid; severe life-threatening complications resulting from standard aneurysm treatments that will likely prevent completion of the study; patient unsuitable for the study, in the opinion of the investigator(s).
Patient Involvement:
Patient will be randomized to one of 5 arms. Patient will be given either placebo or active drug depending on arm.
Primary Outcome:
The study is to determine whether APAP, NAC, and APAP with NAC will inhibit lipid peroxidation in (aSAH), utilizing F2-IsoPs as biomarkers for lipid peroxidation. The effect on the F2-IsoPs will be the primary study endpoint.
Secondary Outcome:
To determine whether APAP and APAP with NAC will inhibit vasospasm and brain ischemia in aSAH, as assessed by CTA w/perfusion imaging or MRI and diffusion weighted images.
Source of Information:
Clinical Trials.gov
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This information last updated on: 11/23/2008
Reviewed on: 06/16/2009.
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