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

Van Der Worp HB, Macleod MR, Bath PMW, Bathula R, Christensen H, Colam B, Cordonnier C, Demotes-Mainard J, Durand-Zaleski I, Gluud C, Jakobsen JC, Kallmünzer B, Kollmar R, Krieger DW, Lees KR, Michalski D, Molina C, Montaner J, Roine RO, Petersson J, Perry R, Sprigg N, Staykov D, Szabo I, Vanhooren G, Wardlaw JM, Winkel P, Schwab S, Hobohm C, Schneider H, Wartenberg K, Berrouschot J, Lorenz M, Christensen HC, Sprigg N, Bathula R, Fitzsimmons P, Perry R, Saastamoinen K, Creagh-Brown BC, Sweenie A, Lindert R, Rubiera M, Serenal J, Vanhooren G, Desfontaines P, Cordonnier C, Sibon I, Jatuzis D, Orzi F (2019)

Publication Type: Journal article

Publication year: 2019


Book Volume: 4

Pages Range: 254-262

Journal Issue: 3

DOI: 10.1177/2396987319844690


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 degrees 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 degrees 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.

Authors with CRIS profile

Involved external institutions

University of Edinburgh GB United Kingdom (GB) University of Nottingham GB United Kingdom (GB) University of Copenhagen DK Denmark (DK) Royal Liverpool and Broadgreen University Hospitals NHS Trust GB United Kingdom (GB) The Griffin Institute - Northwick Park Institute for Medical Research (NPIMR) GB United Kingdom (GB) Copenhagen University Hospital DK Denmark (DK) AZ Sint-Jan NL Netherlands (NL) Newcastle upon Tyne Hospitals NHS Foundation Trust GB United Kingdom (GB) Sheffield Teaching Hospitals NHS Foundation Trust GB United Kingdom (GB) NHS Royal Surrey NHS Foundation Trust GB United Kingdom (GB) Vilnius University Hospital Santaros Klinikos / Vilniaus Universiteto ligoninė Santaros klinikos LT Lithuania (LT) Centre Hospitalier Régional Universitaire de Lille (CHRU de Lille) FR France (FR) European Stroke Research Network for Hypothermia (EuroHYP-1) BE Belgium (BE) Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux FR France (FR) Centre Hospitalier Chrétien – CHC BE Belgium (BE) Hospital Universitari Dr. Josep Trueta ES Spain (ES) Azienda ospedaliera Sant'Andrea IT Italy (IT) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron ES Spain (ES) University of Glasgow GB United Kingdom (GB) Skåne University Hospital / Skånes universitetssjukhus SE Sweden (SE) Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE) LILLE 1 University - Science and Technology FR France (FR) University Medical Centre Utrecht (UMC Utrecht) NL Netherlands (NL) Bispebjerg Hospital DK Denmark (DK) King's College Hospital (KCH) GB United Kingdom (GB) Turku University Hospital / Turun yliopistollinen keskussairaala (TYKS) FI Finland (FI) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Klinikum Altenburger Land DE Germany (DE) Mediclinic Middle East AE United Arab Emirates (AE) Klinikum Darmstadt DE Germany (DE) Martin-Luther-Universität Halle-Wittenberg (MLU) DE Germany (DE) Universität Leipzig DE Germany (DE) University College London Hospitals (UCLH) GB United Kingdom (GB) Université Paris-Est Créteil FR France (FR)

How to cite


Van Der Worp, H.B., Macleod, M.R., Bath, P.M.W., Bathula, R., Christensen, H., Colam, B.,... Orzi, F. (2019). Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial. European Stroke Journal, 4(3), 254-262.


Van Der Worp, H. Bart, et al. "Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial." European Stroke Journal 4.3 (2019): 254-262.

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