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

J 2019

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

WORP VAN DER, H. B,, M. R. MACLEOD, P. M. W. BATH, R. BATHULA, H. CHRISTENSEN et. al.

Basic information

Original name

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

Authors

Edition

EUROPEAN STROKE JOURNAL, LONDON, SAGE PUBLICATIONS LTD, 2019, 2396-9873

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30210 Clinical neurology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

RIV identification code

RIV/00216224:14110/19:00121485

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1177/2396987319844690

UT WoS

000485316800007

Keywords in English

Ischaemic stroke; randomised trial; treatment; hypothermia; cooling

Abstract

V originále

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.

Links

90090, large research infrastructures

Name: CZECRIN II

Citovat

WORP VAN DER, H. B,, M. R. MACLEOD, P. M. W. BATH, R. BATHULA, H. CHRISTENSEN, B. COLAM, C. CORDONNIER, J. DEMOTES-MAINARD, I. DURAND-ZALESKI, C. GLUUD, J. C. JAKOBSEN, B. KALLMUNZERI, R. KOLLMAR, D. W. KRIEGER, K. R. LEES, D. MICHALSKI, C. MOLINA, J. MONTANER, R. O. ROINE, J. PETERSSON, R. PERRY, N. SPRIGG, D. STAYKOV, I. SZABO, G. VANHOOREN, J. M. WARDLAW, P. WINKEL, S. SCHWAB, S. SCHWAB, C. HOBOHM, H. SCHNEIDER, K. WARTENBERG, J. BERROUSCHOT, M. LORENZ, H. C. CHRISTENSEN, N. SPRIGG, R. BATHULA, P. FITZSIMMONS, R. PERRY, K. SAASTAMOINEN, B. C. CREAGH-BROWN, A. SWEENIE, R. LINDERT, M. RUBIERA, J. SERENAL, G. VANHOOREN, P. DESFONTAINES, C. CORDONNIER, I. SIBON, D. JATUZIS and F. ORZI. Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial. EUROPEAN STROKE JOURNAL. LONDON: SAGE PUBLICATIONS LTD, 2019, vol. 4, No 3, p. 254-262. ISSN 2396-9873. Available from: https://dx.doi.org/10.1177/2396987319844690.

@article{1763958,
   author = {Worp van der, H. B, and Macleod, M. R. and Bath, P. M. W. and Bathula, R. and Christensen, H. and Colam, B. and Cordonnier, C. and DemotesandMainard, J. and DurandandZaleski, I. and Gluud, C. and Jakobsen, J. C. and Kallmunzeri, B. and Kollmar, R. and Krieger, D. W. and Lees, K. R. and Michalski, D. and Molina, C. and Montaner, J. and Roine, R. O. and Petersson, J. and Perry, R. and Sprigg, N. and Staykov, D. and Szabo, I. and Vanhooren, G. and Wardlaw, J. M. and Winkel, P. and Schwab, S. and Schwab, S. and Hobohm, C. and Schneider, H. and Wartenberg, K. and Berrouschot, J. and Lorenz, M. and Christensen, H. C. and Sprigg, N. and Bathula, R. and Fitzsimmons, P. and Perry, R. and Saastamoinen, K. and CreaghandBrown, B. C. and Sweenie, A. and Lindert, R. and Rubiera, M. and Serenal, J. and Vanhooren, G. and Desfontaines, P. and Cordonnier, C. and Sibon, I. and Jatuzis, D. and Orzi, F.},
   article_location = {LONDON},
   article_number = {3},
   doi = {http://dx.doi.org/10.1177/2396987319844690},
   keywords = {Ischaemic stroke; randomised trial; treatment; hypothermia; cooling},
   language = {eng},
   issn = {2396-9873},
   journal = {EUROPEAN STROKE JOURNAL},
   title = {Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial},
   url = {https://journals.sagepub.com/doi/pdf/10.1177/2396987319844690},
   volume = {4},
   year = {2019}
}

TY  - JOUR
ID  - 1763958
AU  - Worp van der, H. B, - Macleod, M. R. - Bath, P. M. W. - Bathula, R. - Christensen, H. - Colam, B. - Cordonnier, C. - Demotes-Mainard, J. - Durand-Zaleski, I. - Gluud, C. - Jakobsen, J. C. - Kallmunzeri, B. - Kollmar, R. - Krieger, D. W. - Lees, K. R. - Michalski, D. - Molina, C. - Montaner, J. - Roine, R. O. - Petersson, J. - Perry, R. - Sprigg, N. - Staykov, D. - Szabo, I. - Vanhooren, G. - Wardlaw, J. M. - Winkel, P. - Schwab, S. - Schwab, S. - Hobohm, C. - Schneider, H. - Wartenberg, K. - Berrouschot, J. - Lorenz, M. - Christensen, H. C. - Sprigg, N. - Bathula, R. - Fitzsimmons, P. - Perry, R. - Saastamoinen, K. - Creagh-Brown, B. C. - Sweenie, A. - Lindert, R. - Rubiera, M. - Serenal, J. - Vanhooren, G. - Desfontaines, P. - Cordonnier, C. - Sibon, I. - Jatuzis, D. - Orzi, F.
PY  - 2019
TI  - Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial
JF  - EUROPEAN STROKE JOURNAL
VL  - 4
IS  - 3
SP  - 254-262
EP  - 254-262
PB  - SAGE PUBLICATIONS LTD
SN  - 23969873
KW  - Ischaemic stroke
KW  - randomised trial
KW  - treatment
KW  - hypothermia
KW  - cooling
UR  - https://journals.sagepub.com/doi/pdf/10.1177/2396987319844690
N2  - 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.
ER  -

WORP VAN DER, H. B,, M. R. MACLEOD, P. M. W. BATH, R. BATHULA, H. CHRISTENSEN, B. COLAM, C. CORDONNIER, J. DEMOTES-MAINARD, I. DURAND-ZALESKI, C. GLUUD, J. C. JAKOBSEN, B. KALLMUNZERI, R. KOLLMAR, D. W. KRIEGER, K. R. LEES, D. MICHALSKI, C. MOLINA, J. MONTANER, R. O. ROINE, J. PETERSSON, R. PERRY, N. SPRIGG, D. STAYKOV, I. SZABO, G. VANHOOREN, J. M. WARDLAW, P. WINKEL, S. SCHWAB, S. SCHWAB, C. HOBOHM, H. SCHNEIDER, K. WARTENBERG, J. BERROUSCHOT, M. LORENZ, H. C. CHRISTENSEN, N. SPRIGG, R. BATHULA, P. FITZSIMMONS, R. PERRY, K. SAASTAMOINEN, B. C. CREAGH-BROWN, A. SWEENIE, R. LINDERT, M. RUBIERA, J. SERENAL, G. VANHOOREN, P. DESFONTAINES, C. CORDONNIER, I. SIBON, D. JATUZIS and F. ORZI. Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial. \textit{EUROPEAN STROKE JOURNAL}. LONDON: SAGE PUBLICATIONS LTD, 2019, vol.~4, No~3, p.~254-262. ISSN~2396-9873. Available from: https://dx.doi.org/10.1177/2396987319844690.

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