PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial

Inger R. De Ridder*, A. H.C.M.L. Schreuder, E. Maasland, Peter J. Koudstaal, Ale Algra, Diederik W.J. Dippel, Heleen M. Den Hertog, H. Maarten A. Van Gemert, A. H.C.M.L. Schreuder, Annemieke Ruitenberg, E. Maasland, Ritu Saxena, Jordie H. Van Tuijl, Ben P.W. Jansen, Renske M. Van Den Berg-Vos, Frederique Vermeij, L. Jaap Kappelle, H. Bart Van Der Worp, H. F. Lingsma, N. El GhannoutiF. Vermey, M. Vermeulen, J. G.P. Tijssen, E. J. Van Dijk

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background and Purpose-Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. Methods-PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Results-Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Conclusions-Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed.

Original languageEnglish
Pages (from-to)977-982
Number of pages6
Issue number4
Publication statusPublished - 1 Apr 2017

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