Lower or Higher Oxygenation Targets in ICU patients with COVID-19 - A secondary Bayesian analysis of the HOT-COVID trial

BACKGROUND: In the Handling Oxygenation Targets in COVID-19 (HOT-COVID) trial, a partial pressure of arterial oxygen (PaO 2) target of 60 mmHg compared to 90 mmHg resulted in more days alive without life support at 90 days in adult ICU patients with coronavirus disease 2019 (COVID-19) and hypoxemia. The trial was stopped after enrolling 726 of 780 planned patients due to slow recruitment. Here, we present the preplanned Bayesian analysis of the HOT-COVID trial.

RESEARCH QUESTION: What are the probabilities of any and of clinically relevant benefits from a PaO 2 target of 60 mmHg versus 90 mmHg in adult ICU patients with COVID-19 and hypoxemia, and is there heterogeneity of treatment effects (HTE) according to selected baseline characteristics?

STUDY DESIGN: and Methods We analyzed days alive without life support and 90-day mortality in the HOT-COVID intention-to-treat population (n=697) using Bayesian general linear models to assess probabilities for benefit or harm, including clinically relevant benefits defined as >1 day alive without life support and >2 percentage points lower 90-day mortality. HTE was evaluated based on baseline SOFA scores, PaO 2:FiO 2, norepinephrine doses, and lactate concentrations.

RESULTS: The mean difference in days alive without life support was 5.7 days (95% credible interval (CrI): 0.2 to 11.2), with a 95.2% probability of clinically relevant benefit and a 98.0% probability of any benefit from the lower PaO 2 target. The risk difference in 90-day mortality was -4.6 percentage points (95% CrI: -11.8 to 2.6), with a 76.5% probability of a clinically relevant benefit from the lower target. HTE analyses revealed potential interaction with baseline norepinephrine dose and lactate concentrations for both outcomes.

INTERPRETATION: In ICU patients with COVID-19 and hypoxemia, we found high probability for a clinically relevant benefit of targeting a PaO 2 of 60 mmHg vs. 90 mmHg on number of days alive without life support.