Paracetamol (Acetaminophen) in Stroke 2 (PAIS 2): 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. Issue 3 (April 2015)

• Record Type: Journal Article
• Authors: de Ridder, Inger R.; de Jong, Frank Jan; den Hertog, Heleen M.; Lingsma, Hester F.; van Gemert, H. Maarten A.; Schreuder, A. H. C. M. L. (Tobien); Ruitenberg, Annemieke; Maasland, E. (Lisette); Saxena, Ritu; Oomes, Peter; van Tuijl, Jordie; Koudstaal, Peter J.; Kappelle, L. Jaap; Algra, Ale; van der Worp, H. Bart; Dippel, Diederik W. J.
• Is Part Of: International journal of stroke. Volume 10:Issue 3(2015:Apr.)
• Page Start: 457
• Page End: 462
• Publication Date: 2015-04
• Subjects: body temperature -- functional outcome -- inflammation -- paracetamol -- stroke; 616.8005
• DOI: 10.1111/ijs.12053
• Languages: English
• ISSNs: 1747-4930

Abstract

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 12 h 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.