ABSTRACT
Background. Remdesivir (RDV) is a potent nucleotide prodrug inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase that has demonstrated efficacy in the treatment of patients hospitalized with moderate to severe COVID-19. This Phase 3 (GS-US-540-9012) double-blind, placebo-controlled study compared the efficacy and safety of 3 days of RDV to standard of care in non-hospitalized, high-risk participants with confirmed COVID-19. Methods. Participants were randomly assigned 1:1 to receive intravenous (IV) RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo. The primary efficacy endpoint was composite COVID-19 hospitalization or all-cause death by day 28 and compared using Cox proportional hazards model with baseline stratification factors as covariates. The primary safety endpoint was proportion of participants with treatment-emergent adverse events. Study enrollment was terminated early for administrative reasons in light of the evolving pandemic. Results. 562 patients underwent randomization and started their assigned treatment (279, RDV;283, placebo). Baseline demographics and characteristics were balanced across arms. Overall, 52% were male, 44% were Hispanic/Latino ethnicity and 30% were ≥ 60 years old. The most common comorbidities were diabetes mellitus (62%), obesity (56%;median BMI, 30.7), and hypertension (48%). Median baseline SARS-CoV-2 RNA nasopharyngeal viral load was 6.2 log10 copies/mL. Treatment with RDV significantly reduced COVID-19 hospitalization or all-cause death by day 28 (HR, 0.13;95% CI, 0.03 - 0.59;p = 0.008;Table 1) compared to placebo. Participants receiving RDV also had significantly lower risk for COVID-19-related medically attended visits or all-cause death by day 28 compared to placebo (HR, 0.19;95% CI, 0.07 - 0.56;p = 0.002;Table 1). No deaths occurred in either arm by day 28. There was no difference between arms in time-weighted average change in nasopharyngeal viral loads from baseline up to day 7. The proportion of patients with AEs was similar between arms (Table 1);the most common AEs in the RDV arm were nausea (11%), headache (6%), and diarrhea (4%). Conclusion. A 3-day course of IV RDV was safe, well tolerated and highly effective at preventing COVID-19 related hospitalization or death in high-risk non-hospitalized COVID-19 patients.
ABSTRACT
Rationale: Significant variability exists in the use of direct versus video laryngoscopy for the intubation of critically ill adults. Concerns regarding risks of infection to healthcare providers have led many experts to recommend the use of video laryngoscopy for intubation of patients with COVID-19. This recommendation is based on the belief that using video laryngoscopy allows more physical distance between the operator and the patient, potentially decreasing the risk to providers. Information on the effect of the COVID-19 pandemic on intubation practices is currently limited. Methods: We conducted a survey of intubation practices in 21 emergency departments and intensive care units participating in either of two randomized trials (clinicaltrials.gov identifiers: NCT03928925 and NCT03787732) within the Pragmatic Critical Care Research Group. At each site, the site investigator estimated the prevalence of various airway practices among 3 groups of patients: 1) patients intubated prior to the COVID-19 pandemic, 2) patients intubated with known or suspected COVID-19, and 3) patients intubated during the pandemic without known or suspected COVID-19. The site investigator provided information on use of personal protective equipment, preintubation fluid bolus administration, preoxygenation, sedative choice, paralytic choice, approach to oxygenation from induction to intubation, approach to laryngoscopy, bougie use, primary operator, and ancillary staff present. The primary outcome was the proportion of intubations at a study site that was estimated to be performed using video laryngoscopy. Results: We received responses from 19 of 21 sites (90%). Investigators reported that video laryngoscopy was used in a median of 65% of intubations [IQR: 50-76%] at their site prior to the pandemic compared with a median of 100% of intubations [IQR: 76-100%] for patients with known or suspected COVID-19 (p= 0.0002). Prior to the pandemic only 2 sites (10.5%) reported using exclusively video laryngoscopy, compared to 10 sites (52.6%) that reported using exclusively video laryngoscopy for COVID-19 patients. For patients without known or suspected COVID-19, use of video versus direct laryngoscopy did not differ significantly between patients intubated before the pandemic and patients intubated during the pandemic. Conclusions: Among patients intubated at 19 emergency departments and intensive care units participating in two ongoing clinical trials, we found that the perceived use of video laryngoscopy was greater for patients with known or suspected COVID-19 compared to patients intubated prior to the pandemic, whereas perceived use of video laryngoscopy for patients without COVID-19 during the pandemic was similar to use prior to the pandemic.
ABSTRACT
Rationale: Positive pressure ventilation (PPV) during tracheal intubation of critically ill adults reduces the risk of peri-procedural hypoxemia. Patients with COVID-19 are at increased risk of hypoxemia during tracheal intubation, but expert guidelines have recommended against the use of PPV for patients with suspected or known COVID-19 based on a concern that PPV may increase aerosolization and the risk of infection of healthcare providers. Evidence informing the impact of these recommendations on the airway management practices for patients with COVID-19 is currently limited. Methods: We conducted a survey of perceived intubation practices in 21 emergency departments (EDs) and intensive care units (ICUs) participating in either of two randomized trials (clinicaltrials.gov identifiers: NCT03928925 and NCT03787732) within the Pragmatic Critical Care Research Group between 9-3-2020 and 10-21-2020. At each site, the site investigator provided information on perceived airway management practices among patients intubated prior to the COVID-19 pandemic and during the pandemic. The primary outcome for this analysis was the use of any PPV, either bag-mask ventilation (BMV) or non-invasive ventilation (NIV), between induction and laryngoscopy. Results: We received responses from 19 of 21 sites (90%). Use of BMV was reported in a median of 35% of intubations [IQR: 0-67%] prior to the pandemic compared with a median of 0% of intubations [IQR: 0-20%] performed among patients with known or suspected COVID-19 (p=0.004). Investigators reported using NIV in a median of 10% of intubations [IQR: 0-25%] prior to the pandemic, compared to 10% [IQR 0-30%] of intubations among patients with known or suspected COVID-19 (p=0.20). Receipt of any positive pressure was reported in 50% [IQR: 0-85%] of intubations prior to the pandemic, compared to 30% [IQR: 0-55%] of intubations among patients with known or suspected COVID-19 (p=0.06) (Figure 1). Conclusions: Based on reported practices at 19 EDs and ICUs participating in either of two ongoing clinical trials, we found that the perceived use of BMV between induction and laryngoscopy decreased in patients with known or suspected COVID-19 while the perceived use of NIV did not change. Despite recommendations to avoid its use, perceived use of PPV remains common among patients with suspected or known COVID-19. This reflects the tension between balancing risk to providers and patients for a condition that places both groups at high risk of peri-procedural complications.