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In this randomized, double-blind trial in 1062 adults hospitalized with Covid-19, remdesivir was superior to placebo in shortening the time to recovery (10 days, vs. 15 days with placebo). The estimates of mortality by day 29 were 11.4% with remdesivir and 15.2% with placebo. The benefit of remdesivir was most apparent in patients who were receiving low-flow oxygen at baseline.

Intravenous idarucizumab, an antibody fragment of a human antibody specific for dabigatran, produced rapid reversal of the anticoagulant effect in patients with bleeding or an urgent surgical indication with no apparent toxic effects or rebound hypercoagulable state. A non–vitamin K antagonist oral anticoagulant, dabigatran etexilate (dabigatran) is an oral thrombin inhibitor that is licensed for the prevention of stroke in patients with nonvalvular atrial fibrillation and for the prevention and treatment of venous thromboembolism. Although dabigatran is associated with less serious bleeding than warfarin, 1 – 3 life-threatening bleeding can occur; in addition, dabigatran-treated patients may require urgent surgery or intervention, and dabigatran can increase the risk of perioperative bleeding. To improve the treatment of such patients, a specific dabigatran-reversal agent would be beneficial. Idarucizumab, a monoclonal antibody fragment, binds dabigatran with an affinity that is 350 times as . . .

A randomized trial comparing a 5-day course of intravenous remdesivir with a 10-day course in patients with Covid-19 pneumonia and hypoxemia who were not yet receiving mechanical ventilation showed no significant differences in outcome related to the duration of treatment.

Among nonhospitalized patients with Covid-19–related symptoms that began less than a week previously, a 3-day course of remdesivir resulted in an 87% lower risk of hospitalization or death than placebo. Adverse effects in the remdesivir group were similar to those in the placebo group.

In a trial involving 1033 patients hospitalized with Covid-19, the addition of baricitinib to remdesivir was associated with shorter recovery time, particularly among patients receiving high-flow oxygen, and with a 30% higher odds of improvement at day 15 than remdesivir alone. Adverse events were less frequent with the combination therapy.

No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.

Remdesivir (RDV), a single diastereomeric monophosphoramidate prodrug that inhibits viral RNA polymerases, has potent in vitro antiviral activity against severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). RDV received the US Food and Drug Administration (FDA)’s emergency use authorization in the United States and approval in Japan for treatment of patients with severe coronavirus disease 2019 (COVID‐19). This report describes two phase I studies that evaluated the safety and pharmacokinetics (PKs) of single escalating and multiple i.v. doses of RDV (solution or lyophilized formulation) in healthy subjects. Lyophilized formulation was evaluated for potential future use in clinical trials due to its storage stability in resource‐limited settings. All adverse events were grade 1 or 2 in severity. Overall, RDV exhibited a linear profile following single‐dose i.v. administration over 2 hours of RDV solution formulation across the dose range of 3–225 mg. Both lyophilized and solution formulations provided comparable PK parameters. High intracellular concentrations of the active triphosphate (~ 220‐fold to 370‐fold higher than the in vitro half‐maximal effective concentration against SARS‐CoV‐2 clinical isolate) were achieved following infusion of 75 mg or 150 mg lyophilized formulation over 30 minutes or 2 hours. Following multiple‐doses of RDV 150 mg once daily for 7 or 14 days, RDV exhibited a PK profile similar to single‐dose administration. Metabolite GS‐441524 accumulated ~ 1.9‐fold after daily dosing. Overall, RDV exhibited favorable safety and PK profiles that supported once‐daily dosing.

Ebola transmission has been ongoing in the Democratic Republic of Congo since August 2018. In this trial of MAb114, REGN-EB3, remdesivir, and ZMapp (as the control), mortality from Ebola virus disease was lower in the MAb114 and REGN-EB3 groups than in the other groups.

The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Patients with venous thromboembolism who had received initial anticoagulant therapy were studied in two trials of dabigatran. Dabigatran was effective in preventing recurrent venous thromboembolism and carried a lower risk of bleeding than warfarin but a higher risk than placebo. Anticoagulant treatment with vitamin K antagonists is recommended for patients with venous thromboembolism. 1 Most patients receive at least 3 months of treatment. Long-term treatment is recommended if there are risk factors for recurrence, such as multiple thrombotic episodes. 1 In the absence of clear contraindications to anticoagulant therapy, the risk of major bleeding is approximately 1% per year with extended vitamin K antagonist therapy after venous thromboembolism. 2 The risk of major bleeding, together with the need for frequent laboratory monitoring and dose adjustments, makes long-term treatment problematic. Dabigatran, a direct thrombin inhibitor, does not require frequent monitoring and dose adjustments. At . . .