Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial

H Bart Van Der Worp, Malcolm R Macleod, Philip Mw Bath, Raj Bathula, Hanne Christensen, Bridget Colam, Charlotte Cordonnier, Jacques Demotes-mainard, Isabelle Durand-zaleski, Christian Gluud, Janus Christian Jakobsen, Bernd Kallmünzer, Rainer Kollmar, Derk W Krieger, Kennedy R Lees, Dominik Michalski, Carlos Molina, Joan Montaner, Risto O Roine, Jesper PeterssonRichard Perry, Nikola Sprigg, Dimitre Staykov, Istvan Szabo, Geert Vanhooren, Joanna M Wardlaw, Per Winkel, Stefan Schwab

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction
We assessed whether modest systemic cooling started within 6 hours of symptom onset improves functional outcome at three months in awake patients with acute ischaemic stroke.

Patients and methods
In this European randomised open-label clinical trial with blinded outcome assessment, adult patients with acute ischaemic stroke were randomised to cooling to a target body temperature of 34.0–35.0°C, started within 6 h after stroke onset and maintained for 12 or 24 h , versus standard treatment. The primary outcome was the score on the modified Rankin Scale at 91 days, as analysed with ordinal logistic regression.

Results
The trial was stopped after inclusion of 98 of the originally intended 1500 patients because of slow recruitment and cessation of funding. Forty-nine patients were randomised to hypothermia versus 49 to standard treatment. Four patients were lost to follow-up. Of patients randomised to hypothermia, 15 (31%) achieved the predefined cooling targets. The primary outcome did not differ between the groups (odds ratio for good outcome, 1.01; 95% confidence interval, 0.48–2.13; p = 0.97). The number of patients with one or more serious adverse events did not differ between groups (relative risk, 1.22; 95% confidence interval, 0.65–1.94; p = 0.52).

Discussion
In this trial, cooling to a target of 34.0–35.0°C and maintaining this for 12 or 24 h was not feasible in the majority of patients. The final sample was underpowered to detect clinically relevant differences in outcomes.

Conclusion
Before new trials are launched, the feasibility of cooling needs to be improved.
Original languageEnglish
Pages (from-to)254-262
JournalEuropean Stroke Journal
Volume4
Issue number3
Early online date20 Apr 2019
DOIs
Publication statusPublished - 1 Sep 2019

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