26 Apr 19. Featured Paper
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 Petersson, Richard Perry, Nikola Sprigg, Dimitre Staykov, Istvan Szabo, Geert Vanhooren, Joanna M Wardlaw, Per Winkel, Stefan Schwab, the EuroHYP-1 investigators
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.