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 Pao 2 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 Pao 2 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, Pao 2 to Fio 2 ratio, norepinephrine doses, and lactate concentrations.

RESULTS: The mean difference in days alive without life support was 5.7 days (95% credible interval [CrI], 0.2-11.2), 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 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 Pao 2 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.