PAIS
Paracetamol (acetaminophen) in stroke
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Status:
Trial began in 2005 and ended on May 1, 2008. 1383 patients have been randomized in 25 centers throughout the Netherlands. The follow up will have been completed on August 1, 2008.
Purpose:
To assess if early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic.
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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Year Started:
2005
Year Finished:
2008
Design:
Randomized, double blind, multi-center trial.
Inclusion Criteria
Patients with a clinical diagnosis of ischemic stroke or primary intracerebral hemorrhage; the possibility to confirm the diagnosis with CT or MRI within 24 hours after inclusion in the study; the possibility to start treatment within 12 hours from onset of symptoms (for patients who noticed symptoms after waking from sleep, the time last seen well is taken as the time of onset of symptoms).
Exclusion Criteria
Patients with a body temperature of less than 36.0°C or more than 39.0°C; a history of liver disease or elevated liver enzymes (ASAT, ALAT, AP, or gamma-GT) to more than twice the upper limit of normal; a history of alcohol abuse; hypersensitivity to acetaminophen; death appearing imminent at the time of inclusion; and any prestroke impairment that has led to dependency (modified Rankin scale (mRS) > 2) and therefore interferes with the assessment of functional outcome.
Patient Involvement:
Patients will be randomized to treatment with acetaminophen
1000 mg, 6 times daily, or to matching placebo, for three days.
Primary Outcome:
Outcomes are assessed by means of the mRS, Barthel Index (BI) and EuroQol, by telephone interview at 3 months. In addition, body temperature after 24 hours of treatment is assessed. The primary outcome is the mRS. The primary effect estimate is the odds ratio of improvement according to the sliding dichotomy approach. Secondary effect analyses are an estimate of the odds ratio for improvement assessed by means of ordinal logistic regression analysis, and the dichotomized mRS (≤2: good outcome, ≥3: poor outcome).
Secondary Outcome:
Secondary effect analyses are an estimate of the odds ratio for improvement assessed by means of ordinal logistic regression analysis, and the dichotomized mRS (≤2: good outcome, ≥3: poor outcome).
Results:
Between March, 2003, and May, 2008, 1400 patients were randomly allocated treatment. 260 (37%) of 697 patients receiving paracetamol and 232 (33%) of 703 receiving placebo improved beyond expectation (adjusted odds ratio [OR] 1.20, 95% CI 0.96-1.50). In a post-hoc analysis of patients with baseline body temperature 37-39 degrees C, treatment with paracetamol was associated with improved outcome (1.43, 1.02-1.97). There were 55 serious adverse events in the paracetamol group (8%) and 70 in the placebo group (10%). These results do not support routine use of high-dose paracetamol in patients with acute stroke. Paracetamol might have a beneficial effect on functional outcome in patients admitted with a body temperature 37-39 degrees C, but this post-hoc finding needs further study.
Source of Information:
BMC Cardiovasc Disord. 2005 Aug 19;5:24.
Abstract from 2008 ISC in Major Ongoing Stroke Trials.
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Web Links and Publications:
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This information last updated on: 10/26/2009
Reviewed on: 10/26/2009.
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