Lower or Higher Oxygenation Targets in Patients With COVID-19 in the ICU: A Secondary Bayesian Analysis of the Handling Oxygenation Targets in COVID-19 Trial

Background
In the Handling Oxygenation Targets in COVID-19 (HOT-COVID) trial, a Pao2 target of 60 mm Hg compared with 90 mm Hg resulted in more days alive without life support at 90 days in adults in the ICU with COVID-19 and hypoxemia. The trial was stopped after enrolling 726 of 780 planned patients because of slow recruitment. Herein, we present the preplanned Bayesian analysis of the HOT-COVID trial.

Research Question
What are the probabilities of any benefits and of clinically relevant benefits resulting from a Pao2 target of 60 mm Hg vs 90 mm Hg in adult patients with COVID-19 and hypoxemia in the ICU and does heterogeneity of treatment effects (HTE) exist 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 Sequential Organ Failure Assessment scores, Pao2 to Fio2 ratio, norepinephrine doses, and lactate concentrations.

Results
The mean difference in days alive without life support was 5.7 days (95% credible interval, 0.2-11.2), with a 95.2% probability of clinically relevant benefit and a 98.0% probability of any benefit from the lower Pao2 target. The risk difference in 90-day mortality was –4.6 percentage points (95% credible interval, –11.8 to 2.6 percentage points), 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 patients with COVID-19 and hypoxemia in the ICU, we found a high probability for a clinically relevant benefit of targeting a Pao2 of 60 mm Hg vs 90 mm Hg on number of days alive without life support.

Clinical Trial Registry
ClinicalTrials.gov; No.: NCT04425031; URL: www.clinicaltrials.gov