A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial

Scand J Trauma Resusc Emerg Med. 2016 Nov 28;24(1):138. doi: 10.1186/s13049-016-0334-0.

Abstract

Background: The TTH48 trial aims to determine whether prolonged duration (48 hours) of targeted temperature management (TTM) at 33 (±1) °C results in better neurological outcomes compared to standard duration (24 hours) after six months in comatose out-of-hospital cardiac arrest (OHCA) patients.

Methods: TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised, controlled superiority trial of 24 and 48 hours of TTM at 33 (±1) ° C performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to ten intensive care units (ICUs) in six Northern European countries. The primary outcome of the study is the Cerebral Performance Category (CPC) score observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor neurological outcomes. The secondary outcomes are as follows: mortality within six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the presence of any adverse events such as cerebral, circulatory, respiratory, gastrointestinal, renal, metabolic measures, infection or bleeding. With the planned sample size, we have 80% power to detect a 15% improvement in good neurological outcomes at a two-sided statistical significance level of 5%.

Discussion: We present a detailed statistical analysis protocol (SAP) that specifies how primary and secondary outcomes should be evaluated. We also predetermine covariates for adjusted analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned SAP will reduce analysis bias and add validity to the findings of this trial on the effect of length of TTM on important clinical outcomes after cardiac arrest.

Trial registration: ClinicalTrials.gov: NCT01689077 , 17 September 2012.

Keywords: Cardiac arrest; Cerebral performance category; Critical care; Heart arrest; Intensive care; Mortality; Out-of-hospital; Randomised controlled trial; Targeted temperature management.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Temperature / physiology*
  • Cardiopulmonary Resuscitation / methods*
  • Europe / epidemiology
  • Female
  • Humans
  • Hypothermia, Induced / methods*
  • Male
  • Middle Aged
  • Out-of-Hospital Cardiac Arrest / mortality
  • Out-of-Hospital Cardiac Arrest / physiopathology
  • Out-of-Hospital Cardiac Arrest / therapy*
  • Single-Blind Method
  • Survival Rate / trends
  • Temperature
  • Time Factors
  • Young Adult

Associated data

  • ClinicalTrials.gov/NCT01689077