Remdesivir for the Prevention of Invasive Mechanical Ventilation or Death in Coronavirus Disease 2019 (COVID-19): A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-1 Cohort Data.
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ABSTRACT:
SUBMITTER: Paules CI
PROVIDER: S-EPMC8436376 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Remdesivir for the Prevention of Invasive Mechanical Ventilation or Death in Coronavirus Disease 2019 (COVID-19): A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-1 Cohort Data.
Paules Catharine I CI Gallagher Shannon K SK Rapaka Rekha R RR Davey Richard T RT Doernberg Sarah B SB Grossberg Robert R Hynes Noreen A NA Ponce Philip O PO Short William R WR Voell Jocelyn J Wang Jing J Yang Otto O OO Wolfe Cameron R CR Lye David C DC Dodd Lori E LE Benson Constance A CA
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20220401 7
This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV. ...[more]
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Project description:From December 2019 to May 22, 2020 the emerging and ever-increasing pandemic of coronavirus 19 (COVID-19) had no effective and safe treatment. Not surprisingly, remdesivir attracted worldwide attention. In a trial published online ahead of print, of 1063 patients, 541 were assigned at random to remdesivir and 522 to placebo. The primary prespecified endpoint was mean recovery time and patients assigned to remdesivir had a mean recovery time of 11 days versus 15 days for those assigned a random to placebo. (p?<?0.001). With respect to mortality, the prespecfied secondary endpoint, 34/538 patients in remdesivir and 54/521 in placebo died after 28 days, yielding a possible 31% reduction that approached but did not achieve statistical significance (p?=?0.059). The only other published trial of remdesivir randomized 237 patients in China. In that trial, 178 patients were assigned at random to remdesivir compared to 79 assigned to placebo. Those assigned at random to remdesivir experienced a possible but nonsignificant 23% faster time to clinical improvement of 21 days compared with 23 for those assigned to placebo [hazard ratio 1.23 [95% CI, 0·87-1.75)]. With respect to mortality there was no suggestion of any benefit. In fact, the mortality rate in those receiving remdesivir was 15% (22/150) compared with 13% (10/77) for those assigned to placebo. Ongoing randomized trials should be designed, conducted and analyzed to provide the necessary reliable data on mortality to resolve the remaining clinical uncertainties.
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Project description:ObjectiveThere are concerns of a high barotrauma rate in coronavirus disease 2019 patients with acute respiratory distress syndrome receiving invasive mechanical ventilation. However, a few studies were published, and reported rates were highly variable. We performed a systematic literature review to identify rates of barotrauma, pneumothorax, and pneumomediastinum in coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation.Data sourcePubMed and Scopus were searched for studies reporting barotrauma event rate in adult coronavirus disease 2019 patients receiving invasive mechanical ventilation.Study selectionWe included all studies investigating adult patients with coronavirus disease 2019 acute respiratory distress syndrome requiring mechanical ventilation. Case reports, studies performed outside ICU setting, and pediatric studies were excluded. Two investigators independently screened and selected studies for inclusion.Data extractionTwo investigators abstracted data on study characteristics, rate of pneumothorax, pneumomediastinum and overall barotrauma events, and mortality. When available, data from noncoronavirus disease 2019 acute respiratory distress syndrome patients were also collected. Pooled estimates for barotrauma, pneumothorax, and pneumomediastinum were calculated.Data synthesisA total of 13 studies with 1,814 invasively ventilated coronavirus disease 2019 patients and 493 noncoronavirus disease 2019 patients were included. A total of 266/1,814 patients (14.7%) had at least one barotrauma event (pooled estimates, 16.1% [95% CI, 11.8-20.4%]). Pneumothorax occurred in 132/1,435 patients (pooled estimates, 10.7%; 95% CI, 6.7-14.7%), whereas pneumomediastinum occurred in 162/1,432 patients (pooled estimates, 11.2%; 95% CI, 8.0-14.3%). Mortality in coronavirus disease 2019 patients who developed barotrauma was 111/198 patients (pooled estimates, 61.6%; 95% CI, 50.2-73.0%). In noncoronavirus disease 2019 acute respiratory distress syndrome patients, barotrauma occurred in 31/493 patients (6.3%; pooled estimates, 5.7%; 95% CI, -2.1% to 13.5%).ConclusionsBarotrauma occurs in one out of six coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation and is associated with a mortality rate of about 60%. Barotrauma rate may be higher than noncoronavirus disease 2019 controls.
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Project description:PurposeLimited mechanical ventilators (MV) during the Coronavirus disease (COVID-19) pandemic have led to the use of non-invasive ventilation (NIV) in hypoxemic patients, which has not been studied well. We aimed to assess the association of NIV versus MV with mortality and morbidity during respiratory intervention among hypoxemic patients admitted with COVID-19.MethodsWe performed a retrospective multi-center cohort study across 5 hospitals during March-April 2020. Outcomes included mortality, severe COVID-19-related symptoms, time to discharge, and final oxygen saturation (SpO2) at the conclusion of the respiratory intervention. Multivariable regression of outcomes was conducted in all hypoxemic participants, 4 subgroups, and propensity-matched analysis.ResultsOf 2381 participants with laboratory-confirmed SARS-CoV-2, 688 were included in the study who were hypoxemic upon initiation of respiratory intervention. During the study period, 299 participants died (43%), 163 were admitted to the ICU (24%), and 121 experienced severe COVID-19-related symptoms (18%). Participants on MV had increased mortality than those on NIV (128/154 [83%] versus 171/534 [32%], OR = 30, 95% CI 16-60) with a mean survival of 6 versus 15 days, respectively. The MV group experienced more severe COVID-19-related symptoms [55/154 (36%) versus 66/534 (12%), OR = 4.3, 95% CI 2.7-6.8], longer time to discharge (mean 17 versus 7.1 days), and lower final SpO2 (92 versus 94%). Across all subgroups and propensity-matched analysis, MV was associated with a greater OR of death than NIV.ConclusionsNIV was associated with lower respiratory intervention mortality and morbidity than MV. However, findings may be liable to unmeasured confounding and further study from randomized controlled trials is needed to definitively determine the role of NIV in hypoxemic patients with COVID-19.
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2022-04-08 | GSE178246 | GEO
Project description:BackgroundIt is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19.MethodsWe conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020-October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis.ResultsComplete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83-2.45 with an I2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29-1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31-0.75], I2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40-0.68], I2 37%) were significantly lower for people with previous macrovascular disease.ConclusionsThis large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup.
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Project description:The pandemic of COVID-19 (Coronavirus Disease-2019) is an extremely contagious respiratory illness due to a novel coronavirus, SARS-CoV-2. Certain drugs have several protein targets and many illnesses share overlapping molecular paths. In such cases, reusing drugs for more than one objective and finding their novice uses can considerably decrease the time in finding new cures for unforeseen diseases. Remdesivir has been recently a strong candidate for the treatment of Covid-19. In this commentary, we have portrayed the structure of the coronavirus in a simple way as well as the site where remdesivir acts. We have also displayed the ongoing clinical trials, as well as a published study that was conducted on compassionate base. The covid-19 pandemic might wean down by the end of summer 2020, but the risk of seasonality exists. Therefore, future disposal of agents such as remdesivir might be crucial for ensuring an efficient treatment, decrease mortality and allow early discharge.Communicated by Ramaswamy H. Sarma.
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Project description:BackgroundThis comparative effectiveness study investigated the effect of remdesivir on in-hospital mortality among patients hospitalized for coronavirus disease 2019 (COVID-19) requiring supplemental oxygen including low-flow oxygen (LFO), high-flow oxygen/noninvasive ventilation (HFO/NIV), or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) across variant of concern (VOC) periods.MethodsPatients hospitalized for COVID-19 between December 2020 and April 2022 and administered remdesivir upon admission were 1:1 propensity score matched to patients not administered remdesivir during their COVID-19 hospitalization. Analyses were stratified by supplemental oxygen requirement upon admission and VOC period. Cox proportional hazards models were used to derive adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for 14- and 28-day mortality.ResultsPatients treated with remdesivir (67 582 LFO, 34 857 HFO/NIV, and 4164 IMV/ECMO) were matched to non-remdesivir patients. Unadjusted mortality rates were significantly lower for remdesivir-treated patients at 14 days (LFO: 6.4% vs. 8.8%; HFO/NIV: 16.8% vs. 19.4%; IMV/ECMO: 27.8% vs. 35.3%) and 28 days (LFO: 9.8% vs. 12.3%; HFO/NIV: 25.8% vs. 28.3%; IMV/ECMO: 41.4% vs. 50.6%). After adjustment, remdesivir treatment was associated with a statistically significant reduction in in-hospital mortality at 14 days (LFO: aHR, 0.72; 95% CI, 0.66-0.79; HFO/NIV: aHR, 0.83; 95% CI, 0.77-0.89; IMV/ECMO: aHR, 0.73; 95% CI, 0.65-0.82) and 28 days (LFO: aHR, 0.79; 95% CI, 0.73-0.85; HFO/NIV: aHR, 0.88; 95% CI, 0.82-0.93; IMV/ECMO: aHR, 0.74; 95% CI, 0.67-0.82) compared with non-remdesivir treatment. Lower risk of mortality among remdesivir-treated patients was observed across VOC periods.ConclusionsRemdesivir treatment is associated with significantly reduced mortality among patients hospitalized for COVID-19 requiring supplemental oxygen upon admission, including those requiring HFO/NIV or IMV/ECMO with severe or critical disease, across VOC periods.
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Project description:BackgroundCoronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with little proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness.ObjectiveTo describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation.MethodsThis prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation for respiratory failure due to COVID-19. Patients will be randomized 1:1 to standard-of-care or to receive core warming via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The primary outcome is patient viral load measured by lower respiratory tract sample. Secondary outcomes include severity of acute respiratory distress syndrome (as measured by PaO2/FiO2 ratio) 24, 48, and 72 hours after initiation of treatment, hospital and intensive care unit length of stay, duration of mechanical ventilation, and 30-day mortality.ResultsResulting data will provide effect size estimates to guide a definitive multi-center randomized clinical trial. ClinicalTrials.gov registration number: NCT04426344.ConclusionsWith growing data to support clinical benefits of elevated temperature in infectious illness, this study will provide data to guide further understanding of the role of active temperature management in COVID-19 treatment and provide effect size estimates to power larger studies.
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Project description:BackgroundPatients requiring mechanical ventilation due to COVID-19 have different characteristics of evolution and outcome compared to the general ICU population. Although early weaning from mechanical ventilation is associated with improved outcomes, inadequate identification of patients unable to be weaned may lead to extubation failure and increased days on mechanical ventilation. Outcomes related to mechanical ventilation weaning in this population are scare and inconclusive. Therefore, the objective of this study was to describe the characteristics of mechanical ventilation weaning in subjects with acute respiratory failure induced by COVID-19.MethodsThis was a multi-center, prospective cohort study. We included adult subjects requiring at least 12 h of mechanical ventilation due to COVID-19 infection admitted to any participating ICUs. Characteristics of the mechanical ventilation weaning and extubation process, as well as clinical results, were the primary outcome variables. Weaning types were defined according to previously described and internationally recognized categories.ResultsThree hundred twenty-six subjects from 8 ICUs were included. A spontaneous breathing trial (SBT) was not performed in 52.1% of subjects. One hundred twenty-eight subjects were extubated, and 29.7% required re-intubation. All the subjects included could be classified by Weaning according to a New Definition (WIND) classification (group 0 = 52.1%, group 1 = 28.5%, group 2 = 8.0%, and group 3 = 11.3%) with statistically significant differences in duration of mechanical ventilation (P < .001) and ICU length of stay (P < .001) between groups.ConclusionsThe mechanical ventilation weaning process in subjects with COVID-19 was negatively affected by the disease, with many subjects never completing an SBT. Even though temporal variables were modified, the clinical outcomes in each weaning group were similar to those previously reported.
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