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PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical
Inger R de Ridder1, Heleen M den Hertog2, H Maarten A van Gemert2
1From the Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands (I.R.d.R., P.J.K., D.W.J.D.); Department of Neurology, Medical Spectrum Twente, Enschede, The Netherlands (H.M.d.H.); Department of Neurology, Meander Medical Center, Amersfoort, The Netherlands (H.M.A.v.G.); Department of Neurology, Zuyderland Medical Center, Heerlen, The Netherlands (A.H.C.M.L.T.S.); Department of Neurology, Admiraal de Ruyter Hospital, Goes, The Netherlands (A.R.); Department of Neurology, Van Weel-Bethesda Hospital, Dirksland, The Netherlands (E.L.M.); Department of Neurology, Maasstad Hospital, Rotterdam, The Netherlands (R.S.); Department of Neurology, Elisabeth Twee Steden Hospital, Tilburg, The Netherlands (J.H.v.T., B.P.W.J.); Department of Neurology, OLVG location West, Amsterdam, The Netherlands (R.M.V.d.B.-V.); Department of Neurology, Franciscus Gasthuis, Rotterdam, The Netherlands (F.V.); Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands (L.J.K., A.A., H.B.v.d.W.); and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands (A.A.). i.deridder@erasmusmc.nl.
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.
Clinical Trial Registration:
URL: http://www.trialregister.nl. Unique identifier: NTR2365.
