TY - JOUR
T1 - Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS)
T2 - a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment
AU - PRECIOUS investigators
AU - de Jonge, Jeroen C
AU - Sluis, Wouter M
AU - Reinink, Hendrik
AU - Bath, Philip M
AU - Woodhouse, Lisa J
AU - Zweedijk, Berber
AU - van de Beek, Diederik
AU - Aamodt, Anne Hege
AU - Alpers, Iris
AU - Ciccone, Alfonso
AU - Csiba, Laszlo
AU - Demotes, Jacques
AU - Kõrv, Janika
AU - Kurkowska-Jastrzebska, Iwona
AU - Dawson, Jesse
AU - Macleod, Malcolm R
AU - Ntaios, George
AU - Poli, Sven
AU - Milionis, Haralampos
AU - Ricci, Stefano
AU - Cenciarelli, Silvia
AU - Candelaresi, Paolo
AU - de Bruijn, Sebastiaan Ftm
AU - Pathansali, Rohan
AU - Krishnan, Kailash
AU - Clarke, Brian
AU - Thomalla, Götz
AU - van der Worp, H Bart
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2024/1
Y1 - 2024/1
N2 - BACKGROUND: Infections and fever after stroke are associated with poor functional outcome or death. We assessed whether prophylactic treatment with anti-emetic, antibiotic, or antipyretic medication would improve functional outcome in older patients with acute stroke.METHODS: We conducted an international, 2∗2∗2-factorial, randomised, controlled, open-label trial with blinded outcome assessment in patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and a score on the National Institutes of Health Stroke Scale ≥ 6. Patients were randomly allocated (1:1) to metoclopramide (oral, rectal, or intravenous; 10 mg thrice daily) vs. no metoclopramide, ceftriaxone (intravenous; 2000 mg once daily) vs. no ceftriaxone, and paracetamol (oral, rectal, or intravenous; 1000 mg four times daily) vs. no paracetamol, started within 24 h after symptom onset and continued for four days. All participants received standard of care. The target sample size was 3800 patients. The primary outcome was the score on the modified Rankin Scale (mRS) at 90 days analysed with ordinal logistic regression and reported as an adjusted common odds ratio (an acOR < 1 suggests benefit and an acOR > 1 harm). This trial is registered (ISRCTN82217627).FINDINGS: From April 2016 through June 2022, 1493 patients from 67 European sites were randomised to metoclopramide (n = 704) or no metoclopramide (n = 709), ceftriaxone (n = 594) or no ceftriaxone (n = 482), and paracetamol (n = 706) or no paracetamol (n = 739), of whom 1471 were included in the intention-to-treat analysis. Prophylactic use of study medication did not significantly alter the primary outcome at 90 days: metoclopramide vs. no metoclopramide (adjusted common odds ratio [acOR], 1.01; 95% CI 0.81-1.25), ceftriaxone vs. no ceftriaxone (acOR 0.99; 95% CI 0.77-1.27), paracetamol vs. no paracetamol (acOR 1.19; 95% CI 0.96-1.47). The study drugs were safe and not associated with an increased incidence of serious adverse events.INTERPRETATION: We observed no sign of benefit of prophylactic use of metoclopramide, ceftriaxone, or paracetamol during four days in older patients with a moderately severe to severe acute stroke.FUNDING: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No: 634809.
AB - BACKGROUND: Infections and fever after stroke are associated with poor functional outcome or death. We assessed whether prophylactic treatment with anti-emetic, antibiotic, or antipyretic medication would improve functional outcome in older patients with acute stroke.METHODS: We conducted an international, 2∗2∗2-factorial, randomised, controlled, open-label trial with blinded outcome assessment in patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and a score on the National Institutes of Health Stroke Scale ≥ 6. Patients were randomly allocated (1:1) to metoclopramide (oral, rectal, or intravenous; 10 mg thrice daily) vs. no metoclopramide, ceftriaxone (intravenous; 2000 mg once daily) vs. no ceftriaxone, and paracetamol (oral, rectal, or intravenous; 1000 mg four times daily) vs. no paracetamol, started within 24 h after symptom onset and continued for four days. All participants received standard of care. The target sample size was 3800 patients. The primary outcome was the score on the modified Rankin Scale (mRS) at 90 days analysed with ordinal logistic regression and reported as an adjusted common odds ratio (an acOR < 1 suggests benefit and an acOR > 1 harm). This trial is registered (ISRCTN82217627).FINDINGS: From April 2016 through June 2022, 1493 patients from 67 European sites were randomised to metoclopramide (n = 704) or no metoclopramide (n = 709), ceftriaxone (n = 594) or no ceftriaxone (n = 482), and paracetamol (n = 706) or no paracetamol (n = 739), of whom 1471 were included in the intention-to-treat analysis. Prophylactic use of study medication did not significantly alter the primary outcome at 90 days: metoclopramide vs. no metoclopramide (adjusted common odds ratio [acOR], 1.01; 95% CI 0.81-1.25), ceftriaxone vs. no ceftriaxone (acOR 0.99; 95% CI 0.77-1.27), paracetamol vs. no paracetamol (acOR 1.19; 95% CI 0.96-1.47). The study drugs were safe and not associated with an increased incidence of serious adverse events.INTERPRETATION: We observed no sign of benefit of prophylactic use of metoclopramide, ceftriaxone, or paracetamol during four days in older patients with a moderately severe to severe acute stroke.FUNDING: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No: 634809.
KW - Fever
KW - Infection
KW - Intracerebral haemorrhage
KW - Ischaemic stroke
KW - Pneumonia
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=85178352005&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.lanepe.2023.100782
DO - https://doi.org/10.1016/j.lanepe.2023.100782
M3 - Article
C2 - 38074444
SN - 2666-7762
VL - 36
SP - 100782
JO - The Lancet Regional Health - Europe
JF - The Lancet Regional Health - Europe
M1 - 100782
ER -