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Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial
BACKGROUND: The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targe...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855491/ https://www.ncbi.nlm.nih.gov/pubmed/27142588 http://dx.doi.org/10.1186/s13063-016-1338-9 |
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author | Kirkegaard, Hans Rasmussen, Bodil S de Haas, Inge Nielsen, Jørgen Feldbæk Ilkjær, Susanne Kaltoft, Anne Jeppesen, Anni Nørregaard Grejs, Anders Duez, Christophe Henri Valdemar Larsen, Alf Inge Pettilä, Ville Toome, Valdo Arus, Urmet Taccone, Fabio Silvio Storm, Christian Skrifvars, Markus B. Søreide, Eldar |
author_facet | Kirkegaard, Hans Rasmussen, Bodil S de Haas, Inge Nielsen, Jørgen Feldbæk Ilkjær, Susanne Kaltoft, Anne Jeppesen, Anni Nørregaard Grejs, Anders Duez, Christophe Henri Valdemar Larsen, Alf Inge Pettilä, Ville Toome, Valdo Arus, Urmet Taccone, Fabio Silvio Storm, Christian Skrifvars, Markus B. Søreide, Eldar |
author_sort | Kirkegaard, Hans |
collection | PubMed |
description | BACKGROUND: The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome. METHODS: The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1–2) or poor (CPC 3–5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients. DISCUSSION: This is the first randomised trial to investigate the effect of the duration of TTM at 33 ± 1 °C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients. TRIAL REGISTRATION: NCT01689077 |
format | Online Article Text |
id | pubmed-4855491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-48554912016-05-05 Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial Kirkegaard, Hans Rasmussen, Bodil S de Haas, Inge Nielsen, Jørgen Feldbæk Ilkjær, Susanne Kaltoft, Anne Jeppesen, Anni Nørregaard Grejs, Anders Duez, Christophe Henri Valdemar Larsen, Alf Inge Pettilä, Ville Toome, Valdo Arus, Urmet Taccone, Fabio Silvio Storm, Christian Skrifvars, Markus B. Søreide, Eldar Trials Study Protocol BACKGROUND: The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome. METHODS: The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1–2) or poor (CPC 3–5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients. DISCUSSION: This is the first randomised trial to investigate the effect of the duration of TTM at 33 ± 1 °C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients. TRIAL REGISTRATION: NCT01689077 BioMed Central 2016-05-04 /pmc/articles/PMC4855491/ /pubmed/27142588 http://dx.doi.org/10.1186/s13063-016-1338-9 Text en © Kirkegaard et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Study Protocol Kirkegaard, Hans Rasmussen, Bodil S de Haas, Inge Nielsen, Jørgen Feldbæk Ilkjær, Susanne Kaltoft, Anne Jeppesen, Anni Nørregaard Grejs, Anders Duez, Christophe Henri Valdemar Larsen, Alf Inge Pettilä, Ville Toome, Valdo Arus, Urmet Taccone, Fabio Silvio Storm, Christian Skrifvars, Markus B. Søreide, Eldar Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial |
title | Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial |
title_full | Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial |
title_fullStr | Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial |
title_full_unstemmed | Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial |
title_short | Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial |
title_sort | time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the tth48 trial): study protocol for a randomised controlled trial |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855491/ https://www.ncbi.nlm.nih.gov/pubmed/27142588 http://dx.doi.org/10.1186/s13063-016-1338-9 |
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