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Published in: Trials 1/2016

Open Access 01-12-2016 | Study protocol

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

Authors: Hans Kirkegaard, Bodil S Rasmussen, Inge de Haas, Jørgen Feldbæk Nielsen, Susanne Ilkjær, Anne Kaltoft, Anni Nørregaard Jeppesen, Anders Grejs, Christophe Henri Valdemar Duez, Alf Inge Larsen, Ville Pettilä, Valdo Toome, Urmet Arus, Fabio Silvio Taccone, Christian Storm, Markus B. Skrifvars, Eldar Søreide

Published in: Trials | Issue 1/2016

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Abstract

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

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Metadata
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
Authors
Hans Kirkegaard
Bodil S Rasmussen
Inge de Haas
Jørgen Feldbæk Nielsen
Susanne Ilkjær
Anne Kaltoft
Anni Nørregaard Jeppesen
Anders Grejs
Christophe Henri Valdemar Duez
Alf Inge Larsen
Ville Pettilä
Valdo Toome
Urmet Arus
Fabio Silvio Taccone
Christian Storm
Markus B. Skrifvars
Eldar Søreide
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1338-9

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