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 Ghannouti & 4 others F. Vermey, M. Vermeulen, J. G.P. Tijssen, E. J. Van Dijk

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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
JournalStroke
Volume48
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

Cite this

De Ridder, I. R., Schreuder, A. H. C. M. L., Maasland, E., Koudstaal, P. J., Algra, A., Dippel, D. W. J., ... Van Dijk, E. J. (2017). PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial. Stroke, 48(4), 977-982. https://doi.org/10.1161/STROKEAHA.116.015957
De Ridder, Inger R. ; Schreuder, A. H.C.M.L. ; Maasland, E. ; Koudstaal, Peter J. ; Algra, Ale ; Dippel, Diederik W.J. ; Den Hertog, Heleen M. ; Van Gemert, H. Maarten A. ; Schreuder, A. H.C.M.L. ; Ruitenberg, Annemieke ; Maasland, E. ; Saxena, Ritu ; Van Tuijl, Jordie H. ; Jansen, Ben P.W. ; Van Den Berg-Vos, Renske M. ; Vermeij, Frederique ; Kappelle, L. Jaap ; Van Der Worp, H. Bart ; Lingsma, H. F. ; El Ghannouti, N. ; Vermey, F. ; Vermeulen, M. ; Tijssen, J. G.P. ; Van Dijk, E. J. / PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) : Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial. In: Stroke. 2017 ; Vol. 48, No. 4. pp. 977-982.
@article{9e70ad3af6f741178c853b72b9e00659,
title = "PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial",
abstract = "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.",
keywords = "acetaminophen, body temperature, stroke, therapy, treatment outcome",
author = "{De Ridder}, {Inger R.} and Schreuder, {A. H.C.M.L.} and E. Maasland and Koudstaal, {Peter J.} and Ale Algra and Dippel, {Diederik W.J.} and {Den Hertog}, {Heleen M.} and {Van Gemert}, {H. Maarten A.} and Schreuder, {A. H.C.M.L.} and Annemieke Ruitenberg and E. Maasland and Ritu Saxena and {Van Tuijl}, {Jordie H.} and Jansen, {Ben P.W.} and {Van Den Berg-Vos}, {Renske M.} and Frederique Vermeij and Kappelle, {L. Jaap} and {Van Der Worp}, {H. Bart} and Lingsma, {H. F.} and {El Ghannouti}, N. and F. Vermey and M. Vermeulen and Tijssen, {J. G.P.} and {Van Dijk}, {E. J.}",
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doi = "10.1161/STROKEAHA.116.015957",
language = "English",
volume = "48",
pages = "977--982",
journal = "Stroke",
issn = "0039-2499",
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De Ridder, IR, Schreuder, AHCML, Maasland, E, Koudstaal, PJ, Algra, A, Dippel, DWJ, Den Hertog, HM, Van Gemert, HMA, Schreuder, AHCML, Ruitenberg, A, Maasland, E, Saxena, R, Van Tuijl, JH, Jansen, BPW, Van Den Berg-Vos, RM, Vermeij, F, Kappelle, LJ, Van Der Worp, HB, Lingsma, HF, El Ghannouti, N, Vermey, F, Vermeulen, M, Tijssen, JGP & Van Dijk, EJ 2017, 'PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial' Stroke, vol. 48, no. 4, pp. 977-982. https://doi.org/10.1161/STROKEAHA.116.015957

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) : Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial. / De Ridder, Inger R.; Schreuder, A. H.C.M.L.; Maasland, E.; Koudstaal, Peter J.; Algra, Ale; Dippel, Diederik W.J.; Den Hertog, Heleen M.; Van Gemert, H. Maarten A.; Schreuder, A. H.C.M.L.; Ruitenberg, Annemieke; Maasland, E.; Saxena, Ritu; Van Tuijl, Jordie H.; Jansen, Ben P.W.; Van Den Berg-Vos, Renske M.; Vermeij, Frederique; Kappelle, L. Jaap; Van Der Worp, H. Bart; Lingsma, H. F.; El Ghannouti, N.; Vermey, F.; Vermeulen, M.; Tijssen, J. G.P.; Van Dijk, E. J.

In: Stroke, Vol. 48, No. 4, 01.04.2017, p. 977-982.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2)

T2 - Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial

AU - De Ridder, Inger R.

AU - Schreuder, A. H.C.M.L.

AU - Maasland, E.

AU - Koudstaal, Peter J.

AU - Algra, Ale

AU - Dippel, Diederik W.J.

AU - Den Hertog, Heleen M.

AU - Van Gemert, H. Maarten A.

AU - Schreuder, A. H.C.M.L.

AU - Ruitenberg, Annemieke

AU - Maasland, E.

AU - Saxena, Ritu

AU - Van Tuijl, Jordie H.

AU - Jansen, Ben P.W.

AU - Van Den Berg-Vos, Renske M.

AU - Vermeij, Frederique

AU - Kappelle, L. Jaap

AU - Van Der Worp, H. Bart

AU - Lingsma, H. F.

AU - El Ghannouti, N.

AU - Vermey, F.

AU - Vermeulen, M.

AU - Tijssen, J. G.P.

AU - Van Dijk, E. J.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

KW - acetaminophen

KW - body temperature

KW - stroke

KW - therapy

KW - treatment outcome

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U2 - 10.1161/STROKEAHA.116.015957

DO - 10.1161/STROKEAHA.116.015957

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De Ridder IR, Schreuder AHCML, Maasland E, Koudstaal PJ, Algra A, Dippel DWJ et al. PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial. Stroke. 2017 Apr 1;48(4):977-982. https://doi.org/10.1161/STROKEAHA.116.015957