PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial
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.
|Persistent URL||dx.doi.org/10.1161/STROKEAHA.116.015957, hdl.handle.net/1765/98645|
de Ridder, I, den Hertog, H.M, van Gemert, H.M.A, Schreuder, T.H.C.M.L, Ruitenberg, A, Maasland, E, … Dippel, D.W.J. (2017). PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial. Stroke. doi:10.1161/STROKEAHA.116.015957