PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690].
BACKGROUND
During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4 degrees C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied.


OBJECTIVE
The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments.


METHODS
Seventy-five (3 x 25) patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.
van Breda
Eric J
EJ
Department of Neurology, University Hospital Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. breda@neuro.fgg.eur.nl
van der Worp
Bart
B
van Gemert
Maarten
M
Meijer
Ron
R
Kappelle
Jaap
J
Koudstaal
Peter J
PJ
Dippel
Diederik W
DW
D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D001831:Body Temperature / Q000187:drug effects*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D005240:Feasibility Studies; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D020521:Stroke / Q000150:complications* / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D007052:Ibuprofen