Dataset Information

Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS): a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment.

ABSTRACT:

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.

SUBMITTER: de Jonge JC

PROVIDER: S-EPMC10698669 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS): a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment.

de Jonge Jeroen C JC Sluis Wouter M WM Reinink Hendrik H Bath Philip M PM Woodhouse Lisa J LJ Zweedijk Berber B van de Beek Diederik D Aamodt Anne Hege AH Alpers Iris I Ciccone Alfonso A Csiba Laszlo L Demotes Jacques J Kõrv Janika J Kurkowska-Jastrzebska Iwona I Dawson Jesse J Macleod Malcolm R MR Ntaios George G Poli Sven S Milionis Haralampos H Ricci Stefano S Cenciarelli Silvia S Candelaresi Paolo P de Bruijn Sebastiaan Ftm SF Pathansali Rohan R Krishnan Kailash K Clarke Brian B Thomalla Götz G van der Worp H Bart HB

The Lancet regional health. Europe 20231201

<h4>Background</h4>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.<h4>Methods</h4>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 haemorrh ...[more]

PMID: 38074444

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Dataset Information

Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS): a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment.

Background

Methods

Findings

Interpretation

Funding

Publications

Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS): a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment.

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