TY - JOUR
T1 - Paracetamol (Acetaminophen) in stroke 2 (PAIS 2)
T2 - Protocol for a randomized, placebo-controlled, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke and a body temperature of 36·5°C or above
AU - de Ridder, Inger R.
AU - de Jong, Frank Jan
AU - den Hertog, Heleen M.
AU - Lingsma, Hester F.
AU - van Gemert, H. Maarten A
AU - Schreuder, A. H C M L Tobien
AU - Ruitenberg, Annemieke
AU - Maasland, E. Lisette
AU - Saxena, Ritu
AU - Oomes, Peter
AU - van Tuijl, Jordie
AU - Koudstaal, Peter J.
AU - Kappelle, L. Jaap
AU - Algra, Ale
AU - van der Worp, H. Bart
AU - Dippel, Diederik W J
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Rationale: In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37·0°C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1·43; 95% confidence interval: 1·02-1·97). This relation was also found in the patients with a body temperature of 36·5°C or higher (odds ratio 1·31; 95% confidence interval 1·01-1·68). These findings need confirmation. Aim: The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36·5°C or above on functional outcome. Design: The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0·05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36·5°C or above will be included within 12h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register. Study outcomes: The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression. Discussion: If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide.
AB - Rationale: In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37·0°C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1·43; 95% confidence interval: 1·02-1·97). This relation was also found in the patients with a body temperature of 36·5°C or higher (odds ratio 1·31; 95% confidence interval 1·01-1·68). These findings need confirmation. Aim: The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36·5°C or above on functional outcome. Design: The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0·05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36·5°C or above will be included within 12h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register. Study outcomes: The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression. Discussion: If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide.
KW - Body temperature
KW - Functional outcome
KW - Inflammation
KW - Paracetamol
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=84924858233&partnerID=8YFLogxK
U2 - 10.1111/ijs.12053
DO - 10.1111/ijs.12053
M3 - Article
C2 - 23692587
AN - SCOPUS:84924858233
SN - 1747-4930
VL - 10
SP - 457
EP - 462
JO - International Journal of Stroke
JF - International Journal of Stroke
IS - 3
ER -