PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial [ISCRTN 74418480].
BACKGROUND
In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1 degrees C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3 degrees C (95% CI: 0.1-0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic.


METHODS
Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level.


CONCLUSIONS
This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one.
van Breda
Eric J
EJ
Erasmus Medical Center Rotterdam, The Netherlands. e.vanbreda@erasmusmc.nl
van der Worp
H Bart
HB
van Gemert
H Maarten A
HM
Algra
Ale
A
Kappelle
L Jaap
LJ
van Gijn
Jan
J
Koudstaal
Peter J
PJ
Dippel
Diederik W J
DW
D000082:Acetaminophen / Q000008:administration & dosage / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D002985:Clinical Protocols; D004311:Double-Blind Method; D005334:Fever / Q000150:complications / Q000517:prevention & control; D006801:Humans; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy*; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000150:complications / Q000188:drug therapy*
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen