Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial.

OBJECTIVE: To evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo. METHODS: In this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality. RESULTS: Two hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32-44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6-12 days) in the favipiravir group and 8 days (IQR: 6-12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571-1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4-11 days) in the favipiravir group and 7 days (IQR: 5-10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events. CONCLUSION: In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.

Appropriateness of antimicrobial use among septic patients managed by the critical care response team: an opportunity for improvement through de-escalation.

Background: Most septic patients managed by critical care response teams (CCRT) are prescribed antimicrobials. Nevertheless, data evaluating their appropriateness are lacking both locally and internationally. The objective was to assess antimicrobial use among septic and non-septic patients managed by CCRT. Setting: Case-control design was used to compare septic (cases) and non-septic (controls) CCRT patients at tertiary care setting. The frequency of antimicrobial use was assessed before and after CCRT activation. The appropriateness of antimicrobial use was assessed at day four post-CCRT, based on standard recommendations, clinical assessment, and culture results. Main results: A total of 157 cases and 158 controls were included. The average age was 61.1 ± 20.4 years, and 54.6% were males, with minor differences between groups. The use of any antimicrobial was 100.0% in cases and 87.3% in controls (p < 0.001). The use of meropenem (68.2% versus 34.8%, p < 0.001) and vancomycin (56.7% versus 25.9%, p < 0.001) were markedly higher in cases than controls. The overall appropriateness was significantly lower in cases than controls (50.7% versus 59.6%, p = 0.047). Individual appropriateness was lowest with meropenem (16.7%) and imipenem (25.0%), and highest with piperacillin/tazobactam (87.1%) and colistin (78.3%). Only 48.5% of antimicrobials prescribed by CCRT were de-escalated by a primary team within four days. Individual appropriateness and de-escalations were not different between groups. Conclusions: Empiric use and inadequate de-escalation of broad-spectrum antimicrobials were major causes for inappropriate antimicrobial use in CCRT patients. Our findings highlight the necessity of urgent implementation of an antimicrobial stewardship program, including training and auditing of antimicrobial prescriptions.