The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial
The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial
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DOI：
10.1016/s1474-4422(09)70051-1
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发表时间：
2009-05-01
期刊：
影响因子：
48
通讯作者：
Dippel, Diederik W. J.
中科院分区：
文献类型：
--
作者：
den Hertog, Heleen M.;van der Worp, H. Bart;Dippel, Diederik W. J.
背景：卒中发作后12-24小时内的高体温与不良功能结局相关。扑热息痛对乙酰氨基酚治疗脑卒中（PAIS）试验旨在评估对乙酰氨基酚早期治疗是否通过降低体温和预防发热改善急性脑卒中患者的功能结局。缺血性卒中或脑出血且体温在36 ℃至39 ℃之间的患者被随机分配治疗，在症状发作后12小时内给予对乙酰氨基酚（每日6 g）或安慰剂。治疗分配基于计算机生成的具有不同区组大小的随机数字列表。根据滑动二分法，主要结局是3个月时改良兰金量表的改善超出预期。研究结果2003年3月至2008年5月，1400例患者被随机分配治疗。697例接受扑热息痛治疗的患者中有260例（37%）和703例接受安慰剂治疗的患者中有232例（33%）的改善超出预期（校正比值比[OR] 1.20，95% CI 0.96-1-50）。在基线体温37-39 ℃患者的事后分析中，对乙酰氨基酚治疗与结局改善相关（1.43，1.02-1.97）。对乙酰氨基酚组有55例严重不良事件（8%），安慰剂组有70例（10%）。解释这些结果不支持急性卒中患者常规使用高剂量对乙酰氨基酚。扑热息痛可能对体温37-39 ℃的患者的功能结局有有益的影响，但这一事后发现需要进一步研究。
Background High body temperature in the first 12-24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing body temperature and preventing fever.Methods In a multicentre, randomised, double-blind, placebo-controlled trial, patients with ischaemic stroke or intracerebral haemorrhage and body temperature between 36 degrees C and 39 degrees C were randomly assigned treatment with paracetamol (6 g daily) or placebo within 12 h from symptom onset. Treatment allocation was based on a computer-generated list of random numbers with varying block size. The primary outcome was improvement beyond expectation on the modified Rankin scale at 3 months, according to the sliding dichotomy approach. This trial is registered, number ISRCTN74418480.Findings 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%).Interpretation 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.