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

Journal

Book Volume: 4

Pages Range: 254-262

Journal Issue: 3

DOI: 10.1177/2396987319844690

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

How to cite

APA:

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. https://doi.org/10.1177/2396987319844690

MLA:

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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