The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study.

OBJECTIVE AND DESIGN: The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. SUBJECTS: The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. TREATMENT: 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. METHODS: The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders. RESULTS: 63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups. CONCLUSION: In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate. TRAIL REGISTRATION: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).

AVIFAVIR for Treatment of Patients With Moderate Coronavirus Disease 2019 (COVID-19): Interim Results of a Phase II/III Multicenter Randomized Clinical Trial.

In May 2020 the Russian Ministry of Health granted fast-track marketing authorization to RNA polymerase inhibitor AVIFAVIR (favipiravir) for the treatment of COVID-19 patients. In the pilot stage of Phase II/III clinical trial, AVIFAVIR enabled SARS-CoV-2 viral clearance in 62.5% of patients within 4 days, and was safe and well-tolerated. Clinical Trials Registration. NCT04434248.

The new bedside ROCky score to predict the complications in patients with intermediate-risk pulmonary embolism.

OBJECTIVE: Pulmonary embolism (PE) remains one of the leading causes of mortality among cardiovascular diseases. We aimed at investigating risk factors of PE complications in patients with intermediate risk and integrate them into a simple model for its' bedside prediction. METHODS: Among 173 patients with PE, 136 were classified as high or intermediate risk. Patients were retrospectively divided into groups of complicated (n = 44) or uncomplicated (n = 92) course. Study endpoints: obstructive shock, recurrent PE, needs for resuscitation/thrombolysis/hemodynamic support and death during 30 days. RESULTS: Predictors of PE complications were: chronic heart failure, diabetes mellitus (DM), atrial fibrillation, permanent risk factor of venous thromboembolism, syncope, positive heart-type fatty acid binding protein (hFABP), positive troponin I, heart rate (HR) ≥ 110 bpm, systolic blood pressure (SBP) ≤ 100 mmHg, creatinine clearance ≤ 70 ml/min. Multivariate logistic regression analysis was used to model a simple predictive score named ROCky (Risk of Complications): HR ≥ 110 bpm (1.5 points), SBP ≤ 100 mmHg (2.5 points), positive hFABP (2 points) and presence of DM (2.5 points). The AUROC of this model was 0.89 to predict any complication, 0.83 for obstructive shock and 0.92 for death from any cause; the optimal cut-off scores for any complication was ≥2.5 points, ≥3.5 for obstructive shock and ≥4.5 points for death within 30 days. CONCLUSION: hFABP, tachycardia, hypotension and DM were identified as the major independent determinants of complications development in patients with pulmonary embolism and may be used in combination as the bedside simple predictive ROCky score for early risk stratification in intermediate-risk group.