Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. FUNDING: US National Institutes of Health and Operation Warp Speed

Design and Implementation of Airway Response Teams to Improve the Practice of Emergency Airway Management

Emergency airway management (EAM) is a commonly performed procedure in the critical care setting. Despite clinical advances that help practitioners identify patients at risk for having a difficult airway, improved airway management tools, and algorithms that guide clinical decision-making, the practice of EAM is associated with significant morbidity and mortality. Evidence suggests that a dedicated airway response team (ART) can help mitigate the risks associated with EAM and provide a framework for airway management in acute settings. We review the risks and challenges related to EAM and describe strategies to improve patient care and outcomes via implementation of an ART

Modes of mechanical ventilation vary between hospitals and intensive care units within a university healthcare system: a retrospective observational study

Abstract Objective As evidence-based guidance to aid clinicians with mechanical ventilation mode selection is scant, we sought to characterize the epidemiology thereof within a university healthcare system and hypothesized that nonconforming approaches could be readily identified. We conducted an exploratory retrospective observational database study of routinely recorded mechanical ventilation parameters between January 1, 2010 and December 31, 2016 from 12 intensive care units. Mode epoch count proportions were examined using Chi squared and Fisher exact tests as appropriate on an inter-unit basis with outlier detection for two test cases via post hoc pairwise analyses of a binomial regression model. Results Final analysis included 559,734 mode epoch values. Significant heterogeneity was demonstrated between individual units (P < 0.05 for all comparisons). One unit demonstrated heightened utilization of high-frequency oscillatory ventilation, and three units demonstrated frequent synchronized intermittent mandatory ventilation utilization. Assist control ventilation was the most commonly recorded mode (51%), followed by adaptive support ventilation (23.1%). Volume-controlled modes were about twice as common as pressure-controlled modes (64.4% versus 35.6%). Our methodology provides a means by which to characterize the epidemiology of mechanical ventilation approaches and identify nonconforming practices. The observed variability warrants further clinical study about contributors and the impact on relevant outcomes

MOESM4 of Modes of mechanical ventilation vary between hospitals and intensive care units within a university healthcare system: a retrospective observational study

Additional file 4: Figure S2. Ratios of mechanical ventilation mode epochs per hospital by intensive care unit type. Hospital 1 NSICUs depicted in aggregate. See list of abbreviations section

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Additional file 6: Figure S4. Ratios of mechanical ventilation mode epochs per hospital. See list of abbreviations section

MOESM1 of Modes of mechanical ventilation vary between hospitals and intensive care units within a university healthcare system: a retrospective observational study

Additional file 1: Table S1. Details of studied hospitals and intensive care units

MOESM2 of Modes of mechanical ventilation vary between hospitals and intensive care units within a university healthcare system: a retrospective observational study

Additional file 2: Figure S1. CONSORT flow diagram

Validation of an admission coagulation panel for risk stratification of COVID-19 patients.

BackgroundThere is limited data on the markers of coagulation and hemostatic activation (MOCHA) profile in Coronavirus disease 2019 (COVID-19) and its ability to identify COVID-19 patients at risk for thrombotic events and other complications.MethodsHospitalized patients with confirmed SARS-COV-2 from four Atlanta hospitals were included in this observational cohort study and underwent admission testing of MOCHA parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer). Clinical outcomes included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, access line thrombosis, ICU admission, intubation and mortality.Main resultsOf 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American), 45 (16%) had a thrombotic endpoint. Each MOCHA parameter was independently associated with a thrombotic event (pConclusionsAn admission MOCHA profile is useful to risk-stratify COVID-19 patients for thrombotic complications and more effective than isolated d-dimer for predicting risk of ICU admission and intubation