Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

Frequency of Continuous Renal Replacement Therapy Use Early in Coronavirus Disease 2019 Pandemic.

OBJECTIVES: A subset of patients with coronavirus disease 2019 develop renal failure and require continuous renal replacement therapy. We reviewed the available literature to understand the frequency of continuous renal replacement therapy use among patients with coronavirus disease 2019 who required intensive care. DATA SOURCES: The authors reviewed PubMed and Google Scholar for published studies and MedRxiv.com for unpublished studies. STUDY SELECTION: Observational and randomized studies that report the frequency of continuous renal replacement therapy use in adult patients with coronavirus disease 2019. DATA EXTRACTION: Data from the eligible studies were extracted independently by two authors into Microsoft Excel. DATA SYNTHESIS: We identified 12 eligible studies (eight published, four unpublished). We found that up to 20% of patients admitted to ICUs may require continuous renal replacement therapy. CONCLUSIONS: Given the high utilization of continuous renal replacement therapy by critically ill patients with coronavirus disease 2019, there may be an urgent need to mobilize inpatient dialysis resources to cope with the anticipated increase in the demand.

Implementing a COVID-19 Discharge Pathway to Improve Patient Safety.

The posthospital discharge period is vulnerable for patients with coronavirus disease 2019 (COVID-19). The authors implemented a COVID-19 discharge pathway in the electronic medical record for UCHealth, a 12-hospital health care system, including an academic medical center (University of Colorado Hospital [UCH]), to improve patient safety by standardizing discharge processes for COVID-19 patients. There were 3 key elements: (1) building consensus on discharge readiness criteria, (2) summarizing discharge criteria for disposition locations, and (3) establishing primary care follow-up protocols. The discharge pathway was opened 821 times between April 20, 2020, and June 7, 2020. Of the 436 patients discharged from the hospital medicine service at UCH from April 20, 2020, and June 7, 2020, 18 (4%) were readmitted and 13 (3%) had a 30-day emergency department visit. The main trend observed was venous thromboembolism. This pathway allowed real-time integration of clinical guidelines and complex disposition requirements, decreasing cognitive burden and standardizing care for a complex population.