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Data on 53 patients treated with investigational antiviral Remdesivir through the compassionate use program


The detailed results of an analysis of 53 patients hospitalized with severe complications of COVID-19 who were treated with the investigational antiviral Remdesivir on an individual compassionate use basis, were published in The New England Journal of Medicine ( NEJM ).
The majority of patients in this international cohort demonstrated clinical improvement and no new safety signals were identified with Remdesivir treatment.
Compassionate use data have limitations and multiple phase 3 studies are ongoing to determine the safety and efficacy of Remdesivir for the treatment of COVID-19.

Nearly two thirds of patients ( 64%, n=34/53) in this cohort were on mechanical ventilation at baseline, including 4 patients also on extracorporeal membrane oxygenation ( ECMO ).
Treatment with Remdesivir resulted in an improvement in oxygen support class for 68% of patients ( n=36/53 ) over a median follow-up of 18 days from the first dose of Remdesivir.
More than half of patients on mechanical ventilation were extubated ( 57%, n=17/30 ) and nearly half of all patients ( 47%, n=25/53 ) were discharged from the hospital following treatment with Remdesivir.
After 28 days of follow-up, the cumulative incidence of clinical improvement, defined as discharge from the hospital and/or at least a two-point improvement from baseline on a predefined six-point scale, was 84% according to Kaplan-Meier analysis.
Clinical improvement was less frequent among patients on invasive ventilation versus noninvasive ventilation ( hazard ratio, HR: 0.33 [ 95% CI 0.16, 0.68 ] ) and among patients at least 70 years of age ( HR vs less than 50 years: 0.29 [ 95% CI 0.11, 0.74 ] ).

Compassionate use data have limitations due to the small size of the cohort, the relatively short duration of follow-up, potential missing data due to the nature of the program and lack of a randomized control group.

The overall mortality rate in this cohort was 13% ( n=7/53 ). The mortality rate was higher in the subgroup of patients on invasive ventilation ( 18%, n=6/34 ), compared with patients on noninvasive oxygen support ( 5%, n=1/19 ).
Factors associated with an increased risk of mortality included age greater than 70 years ( HR vs less than 70 years: 11.34 [ 95% CI 1.36, 94.17 ] ) and higher baseline serum creatinine levels ( HR per mg/dL: 1.91 [ 95% CI 1.22, 2.99 ] ), indicating reduced kidney function.

Mild to moderate liver enzyme ( ALT and/or AST ) elevations ( 23%, n=12/53 ) were observed in this cohort.
No new safety signals were detected during short-term remdesivir therapy.

Given the limitations of this data set and analysis, data from ongoing, randomized clinical studies of Remdesivir are needed to provide a scientifically robust understanding of the clinical impact of remdesivir treatment.

More than 1,800 patients have been treated with Remdesivir through individual compassionate use protocols.

Data from 53 patients in the United States, Europe, Canada and Japan who received at least one dose of Remdesivir on or before March 7, 2020, through compassionate use program, were evaluated.
All patients were hospitalized with severe acute respiratory coronavirus 2 ( SARS-CoV-2 ) infection and either an oxygen saturation of 94% or less, or a need for oxygen.
The median duration of symptoms before initiation of Remdesivir was 12 days.
The majority of patients ( 75% ) were men over the age of 60 years with comorbid conditions, including hypertension, diabetes, hyperlipidemia and asthma. Combined, all three of these factors have been associated with adverse outcomes of COVID-19.
The planned treatment was a 10-day course of Remdesivir, consisting of a 200 mg loading dose administered intravenously on day 1, followed by 100 mg daily for the remaining nine treatment days. Of the 53 patients included in the analysis, 75% received the full 10-day course of Remdesivir, 19% received 5-9 days of treatment, and 6% received fewer than 5 days of treatment.
Follow-up continued through 28 days after initiation of Remdesivir treatment.
Four patients discontinued Remdesivir prematurely, one due to worsening of pre-existing renal failure, one due to multiple organ failure and two due to elevated liver enzymes, including one patient with a maculopapular rash.

There were no prespecified endpoints for this program. As part of the analysis, rates of key clinical events were quantified, including change in oxygen support requirements, hospital discharge, reported adverse events leading to discontinuation of Remdesivir treatment and mortality.
In addition, the analysis evaluated the proportion of patients with clinical improvement, defined as live discharge from the hospital and/or a clinical improvement of at least two points from baseline on a six-point scale reflecting hospitalization and oxygen support status, as recommended by the World Health Organization R&D Blueprint Group.

Remdesivir is an investigational nucleotide analog with broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple emerging viral pathogens, including Ebola, Marburg, MERS and SARS.
In vitro testing conducted by Gilead has demonstrated that Remdesivir is active against the virus that causes COVID-19. ( Xagena )

Source: Gilead, 2020

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