Handling Oxygenation Targets in the Intensive Care Unit (HOT‐ICU)—Protocol for a randomised clinical trial comparing a lower vs a higher oxygenation target in adults with acute hypoxaemic respiratory failure

Abstract

Background: Acutely ill adults with hypoxaemic respiratory failure are at risk of lifethreatening hypoxia, and thus oxygen is often administered liberally. Excessive oxygen use may, however, increase the number of serious adverse events, including death. Establishing the optimal oxygenation level is important as existing evidence is of low quality. We hypothesise that targeting an arterial partial pressure of oxygen (PaO 2 ) of 8 kPa is superior to targeting a PaO 2 of 12 kPa in adult intensive care unit (ICU) patients with acute hypoxaemic respiratory failure. Methods:The Handling Oxygenation Targets in the ICU (HOT-ICU) trial is an outcome assessment blinded, multicentre, randomised, parallel-group trial targeting PaO 2 in acutely ill adults with hypoxaemic respiratory failure within 12 hours after ICU admission. Patients are randomised 1:1 to one of the two PaO 2 targets throughout ICU stay until a maximum of 90 days. The primary outcome is 90-day mortality.Secondary outcomes are serious adverse events in the ICU, days alive without organ support and days alive out of hospital in the 90-day period; mortality, health-related | 957 SCHJØRRING et al.

Bayesian and heterogeneity of treatment effect analyses of the HOT‐ICU trial—A secondary analysis protocol

“…The HOT‐ICU trial is an ongoing, international, randomised, parallel group, investigator‐initiated trial of a lower versus a higher oxygenation target, conducted in adult patients (≥18 years) acutely admitted to the ICU with hypoxaemic respiratory failure 6,7 . Patients are randomised 1:1 to either an arterial partial pressure of oxygen (PaO 2 ) target of 8 kPa (intervention) or 12 kPa (control) during their ICU stay, including re‐admissions up to 90 days after inclusion.…”

“…Patients are randomised 1:1 to either an arterial partial pressure of oxygen (PaO 2 ) target of 8 kPa (intervention) or 12 kPa (control) during their ICU stay, including re‐admissions up to 90 days after inclusion. Complete enrolment criteria are available in the primary trial protocol 6 and the supplement. The primary outcome is 90‐day all‐cause mortality, which is the only outcome that will be assessed in this secondary analysis.…”

“…We hypothesise an overall reduction in all‐cause 90‐day mortality with a lower oxygenation target as compared with a higher target 6,7 . Also, we hypothesise that patients with greater baseline severity of illness, higher degree of hypoxaemic respiratory failure, requirement for higher dose of noradrenalin, or higher concentration of plasma lactate will have greater reductions in 90‐day all‐cause mortality with a lower oxygenation target as compared with a higher target.…”

“…The ongoing Handling Oxygenation Targets in the Intensive Care Unit (HOT‐ICU) trial compares a lower versus a higher oxygenation target in adult patients acutely admitted to the ICU with hypoxaemic respiratory failure 6,7 . The results from this trial will more than double the available data, and improve the knowledge on the optimal oxygenation target in adult ICU patients with hypoxaemia.…”

Trials on oxygen supplementation in sepsis: better late than never

“…However, none of the trials are focused specifically on sepsis; the enrol patients with acute hypoxia, systemic inflammatory response syndrome or ARDS (Table 1). And none of the ongoing trials are likely to provide a large sub-group of patients with sepsis to substantially increase the certain of the effect estimates observed in the ICU-ROX sub-group; the HOT-ICU trial is the only large trial ongoing, but the presence of sepsis is not registered at baseline in that trial [11]. A large subgroup of patients with sepsis will likely be included in the MEGA-ROX trial planned by the ICU-ROX investigators.…”