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Annals of Internal Medicine May 2022Remdesivir is approved for the treatment of adults hospitalized with COVID-19. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Remdesivir is approved for the treatment of adults hospitalized with COVID-19.
PURPOSE
To update a living review of remdesivir for adults with COVID-19.
DATA SOURCES
Several electronic U.S. Food and Drug Administration, company, and journal websites from 1 January 2020 through 19 October 2021.
STUDY SELECTION
English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19.
DATA EXTRACTION
One reviewer abstracted, and a second reviewer verified data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used.
DATA SYNTHESIS
Since the last update (search date 9 August 2021), 1 new RCT and 1 new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified. This review summarizes and updates the evidence on the cumulative 5 RCTs and 2 subtrials for this comparison. Our updated results confirm a 10-day course of remdesivir, compared with control, probably results in little to no mortality reduction (5 RCTs). Updated results also confirm that remdesivir probably results in a moderate increase in the proportion of patients recovered by day 29 (4 RCTs) and may reduce time to clinical improvement (2 RCTs) and hospital length of stay (4 RCTs). New RCTs, by increasing the strength of evidence, lead to an updated conclusion that remdesivir probably results in a small reduction in the proportion of patients receiving ventilation or extracorporeal membrane oxygenation at specific follow-up times (4 RCTs). New RCTs also alter the conclusions for harms-remdesivir, compared with control, may lead to a small reduction in serious adverse events but may lead to a small increase in any adverse event.
LIMITATION
The RCTs differed in definitions of COVID-19 severity and outcomes reported.
CONCLUSION
In hospitalized adults with COVID-19, the findings confirm that remdesivir probably results in little to no difference in mortality and increases the proportion of patients recovered. Remdesivir may reduce time to clinical improvement and may lead to small reductions in serious adverse events but may result in a small increase in any adverse event.
PRIMARY FUNDING SOURCE
U.S. Department of Veterans Affairs.
Topics: Adenosine Monophosphate; Adult; Alanine; Humans; Physicians; United States; COVID-19 Drug Treatment
PubMed: 35226522
DOI: 10.7326/M21-4784 -
Jornal Brasileiro de Pneumologia :... 2022Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the use of remdesivir for the treatment of patients hospitalized with moderate to severe COVID-19.
METHODS
This was a systematic review and meta-analysis including phase 3 randomized clinical trials (RCTs) and observational cohort studies selected from various databases, comparing patients hospitalized with moderate to severe COVID-19 receiving remdesivir and controls.
RESULTS
A total of 207 studies were retrieved, 9 of which met the eligibility criteria and were included in the study. The meta-analysis using RCTs alone showed no statistically significant differences regarding mortality or use of mechanical ventilation/extracorporeal membrane oxygenation between remdesivir and control groups, and the quality of evidence was moderate and low, respectively. The use of remdesivir increased the recovery rate by 6% (95% CI, 3-9); p = 0.004) and the clinical improvement rate by 7% (95% CI, 1-14); p = 0.02). Additionally, no significant differences in mortality were found between remdesivir and control groups when the meta-analysis used observational cohort studies alone (risk difference = -0.01 (95% CI, -0.02 to 0.01; p = 0.32), the quality of evidence being moderate, and the risk of adverse events was 4% ([95% CI, -0.08 to 0.01]; p = 0.09).
CONCLUSIONS
The use of remdesivir for the treatment of patients with moderate to severe COVID-19 had no significant impact on clinically important outcomes.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; Observational Studies as Topic; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 35137874
DOI: 10.36416/1806-3756/e20210393 -
PloS One 2021Effective drug treatments for Covid-19 are needed to decrease morbidity and mortality for the individual and to alleviate pressure on health care systems. Remdesivir... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Effective drug treatments for Covid-19 are needed to decrease morbidity and mortality for the individual and to alleviate pressure on health care systems. Remdesivir showed promising results in early randomised trials but subsequently a large publicly funded trial has shown less favourable results and the evidence is interpreted differently in clinical guidelines. Systematic reviews of remdesivir have been published, but none have systematically searched for unpublished data, including regulatory documents, and assessed the risk of bias due to missing evidence.
METHODS
We will conduct a systematic review of randomised trials comparing remdesivir to placebo or standard of care in any setting. We will include trials regardless of the severity of disease and we will include trials examining remdesivir for indications other than Covid-19 for harms analyses. We will search websites of regulatory agencies, trial registries, bibliographic databases, preprint servers and contact trial sponsors to obtain all available data, including unpublished clinical data, for all eligible trials. Our primary outcomes will be all-cause mortality and serious adverse events. Our secondary outcomes will be length of hospital stay, time to death, severe disease, and adverse events. We will assess the risk of bias using the Cochranes Risk of Bias 2 tool and the risk of bias due to missing evidence (e.g. publication bias, selective reporting bias) using the ROB-ME tool. Where appropriate we will synthesise study results by conducting random-effects meta-analysis. We will present our findings in a Summary of Findings table and rate the certainty of the evidence using the GRADE approach.
DISCUSSION
By conducting a comprehensive systematic review including unpublished data (where available), we expect to be able to provide valuable information for patients and clinicians about the benefits and harms of remdesivir for the treatment of Covid-19. This will help to ensure optimal treatment for individual patients and optimal utilisation of health care resources.
SYSTEMATIC REVIEW REGISTRATION
CRD42021255915.
Topics: Adenosine Monophosphate; Adult; Alanine; Humans; Publication Bias; Risk; COVID-19 Drug Treatment
PubMed: 34843589
DOI: 10.1371/journal.pone.0260544 -
Journal of the American College of... Oct 2021Patients undergoing early surgery after coronary stent implantation are at increased risk for mortality from ischemic and hemorrhagic complications. The optimal...
Patients undergoing early surgery after coronary stent implantation are at increased risk for mortality from ischemic and hemorrhagic complications. The optimal antiplatelet strategy in patients who cannot discontinue dual antiplatelet therapy (DAPT) before surgery is unclear. Current guidelines, based on surgical and clinical characteristics, provide risk stratification for bridging therapy with intravenous antiplatelet agents, but management is guided primarily by expert opinion. This review summarizes perioperative risk factors to consider before discontinuing DAPT and reviews the data for intravenous bridging therapies. Published reports have included bridging options such as small molecule glycoprotein IIb/IIIa inhibitors (eptifibatide or tirofiban) and cangrelor, an intravenous P2Y inhibitor. However, optimal management of these complex patients remains unclear in the absence of randomized controlled data, without which an argument can be made both for and against the use of perioperative intravenous bridging therapy after discontinuing oral P2Y inhibitors. Multidisciplinary risk assessment remains a critical component of perioperative care.
Topics: Adenosine Monophosphate; Eptifibatide; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Stents; Thromboembolism; Tirofiban
PubMed: 34620413
DOI: 10.1016/j.jacc.2021.08.013 -
The Cochrane Database of Systematic... Aug 2021Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to...
BACKGROUND
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID-19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required.
OBJECTIVES
To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS-CoV-2 infection, and to maintain the currency of the evidence using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021.
SELECTION CRITERIA
We followed standard Cochrane methodology. We included RCTs evaluating remdesivir for the treatment of SARS-CoV-2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting. We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all-cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high-flow oxygen or non-invasive or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non-invasive mechanical ventilation or high-flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, adverse events (any grade), and serious adverse events.
MAIN RESULTS
We included five RCTs with 7452 participants diagnosed with SARS-CoV-2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low-flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. We identified two ongoing studies, one was suspended due to a lack of COVID-19 patients to recruit. Risk of bias was considered to be of some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data. Effects of remdesivir in hospitalised individuals Remdesivir probably makes little or no difference to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate-certainty evidence). Considering the initial severity of condition, only one study showed a beneficial effect of remdesivir in patients who received low-flow oxygen at baseline (RR 0.32, 95% CI 0.15 to 0.66, 435 participants), but conflicting results exists from another study, and we were unable to validly assess this observations due to limited availability of comparable data. Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low-certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low-certainty evidence). We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high-flow oxygen or non-invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low-certainty evidence); new need for non-invasive mechanical ventilation or high-flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low-certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low-certainty evidence). The evidence suggests that remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low-certainty evidence). None of the included studies reported quality of life. Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate-certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Based on the currently available evidence, we are moderately certain that remdesivir probably has little or no effect on all-cause mortality at up to day 28 in hospitalised adults with SARS-CoV-2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to validly examine the effect of remdesivir on mortality in subgroups depending on the extent of respiratory support at baseline. Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Bias; COVID-19; Cause of Death; Confidence Intervals; Disease Progression; Humans; Middle Aged; Oxygen; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Ventilator Weaning; COVID-19 Drug Treatment
PubMed: 34350582
DOI: 10.1002/14651858.CD014962 -
Infection Feb 2022This review was aimed to synthesise the best available evidence on the effectiveness and safety of remdesivir in the treatment of moderate to severe COVID-19. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This review was aimed to synthesise the best available evidence on the effectiveness and safety of remdesivir in the treatment of moderate to severe COVID-19.
METHOD
Randomised controlled trials (RCTs) and observational studies reporting the effectiveness and safety of remdesivir were searched via databases and other sources from December 2019 to December 2020. Two independent reviewers performed literature screening, data extraction and assessment of risk bias. Seven studies involving 3686 patients were included.
RESULTS
Treatment with remdesivir was associated with an increase in clinical recovery rate by 21% (RR 1.21; 95% CI 1.08-1.35) on day 7 and 29% (RR 1.29; 95% CI 1.22-1.37) on day 14. The likelihoods of requiring high-flow supplemental oxygen and invasive mechanical ventilation in the remdesivir group were lower than in the placebo group by 27% (RR 0.73; 95% CI 0.54-0.99) and 47% (RR 0.53; 95% CI 0.39-0.72), respectively. Remdesivir-treated patients showed a 39% (RR 0.61; 95% CI 0.46-0.79) reduction in the risk of mortality on day 14 compared to the control group; however, there was no significant difference on day 28. Serious adverse effects (SAEs) were significantly less common in patients treated with remdesivir, with an absolute risk difference of 6% (RD -0.06; 95% CI -0.09 to -0.03).
CONCLUSION
Despite conditional recommendation against its use, remdesivir could still be effective in early clinical improvement; reduction of early mortality and avoiding high-flow supplemental oxygen and invasive mechanical ventilation among hospitalised COVID-19 patients. Remdesivir was also well tolerated without significant SAEs compared to placebo, yet available evidence from clinical studies support the need to conduct close monitoring.
Topics: Adenosine Monophosphate; Alanine; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34331674
DOI: 10.1007/s15010-021-01671-0 -
Journal of Microbiology, Immunology,... Oct 2021Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2... (Review)
Review
Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.
Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Carbamates; Cobicistat; Darunavir; Dibenzothiepins; Drug Combinations; Drug Therapy, Combination; Humans; Imidazoles; Indoles; Iran; Lopinavir; Morpholines; Pyrazines; Pyridones; Pyrrolidines; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Sofosbuvir; Treatment Outcome; Triazines; Valine; COVID-19 Drug Treatment
PubMed: 34253490
DOI: 10.1016/j.jmii.2021.05.011 -
Expert Review of Anti-infective Therapy Feb 2022We systematically reviewed the evidence of published original research to determine the role of remdesivir in the management of patients with COVID-19 and a...
OBJECTIVE
We systematically reviewed the evidence of published original research to determine the role of remdesivir in the management of patients with COVID-19 and a moderate-to-severe course of illness.
METHODS
A systematic search of articles was conducted in scientific databases, with the latest update in May 2021. This paper systematically reviewed the clinical evidence available (randomized controlled trials, compassionate use studies, and case reports) on the use of remdesivir for patients with moderate or severe COVID-19.
RESULTS
A total of eleven studies were included: four studies based on compassionate use of remdesivir, three randomized, double-blind, placebo-controlled, multicentre trials, three randomized, open-label, phase III trials, and one case report. Clinical improvement and mortality rates in patients who used remdesivir varied across studies.
CONCLUSION
Given the current evidence, there is insufficient data to confidently recommend the use of remdesivir alone for the treatment of adult hospitalized patients with moderate-to-severe COVID-19. However, remdesivir may be considered along with an anti-inflammatory agent in patients with pneumonia, on oxygen support, provided there is close monitoring of clinical and laboratory parameters and adverse events.
Topics: Adenosine Monophosphate; Adult; Alanine; Antiviral Agents; Clinical Trials, Phase III as Topic; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34192469
DOI: 10.1080/14787210.2021.1949984 -
BMJ Open Jun 2021Evaluation of remdesivir, an RNA polymerase inhibitor, for effectiveness in adults with COVID-19. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Evaluation of remdesivir, an RNA polymerase inhibitor, for effectiveness in adults with COVID-19.
DATA SOURCES
Electronic search for eligible articles of PubMed, Cochrane Central and clinicaltrials.gov was performed on 20 September 2020.
PARTICIPANTS AND STUDY ELIGIBILITY CRITERIA
Only randomised controlled trials (RCTs) evaluating efficacy of remdesivir in COVID-19 were included for meta-analysis.
INTERVENTIONS
Remdesivir was compared with standard of care.
PRIMARY AND SECONDARY OUTCOMES
Primary outcome was mortality and secondary outcomes were time to clinical improvement and safety outcomes like serious adverse events, respiratory failure.
STUDY APPRAISAL AND SYNTHESIS METHODS
Data synthesis was done with Cochrane review manager 5 (RevMan) V.5.3. Cochrane risk of bias V.2.0 tool was used for methodological quality assessment. The GRADE pro GDT was applied for overall quality of evidence.
RESULTS
52 RCTs were screened and 4 studies were included in analysis, with total of 7324 patients. No mortality benefit was observed with remdesivir versus control group (OR=0.92 (95% CI 0.79 to 1.07), p=0.30, moderate quality evidence). Significantly higher rates of clinical improvement (OR=1.52 (95% CI 1.24 to 1.87), p<0.0001, low quality) and faster time to clinical improvement (HR=1.28 (95% CI 1.12 to 1.46), p=0.0002, very low quality) was observed with remdesivir versus control group. Significant decrease was found in the risk of serious adverse events (RR=0.75 (95% CI 0.62 to 0.90), p=0.0003, low quality); however, no difference was found in the risk of respiratory failure (RR=0.85 (95% CI 0.41 to 1.77), p=0.67, very low quality evidence) with remdesivir.
CONCLUSIONS
As per the evidence from current review, remdesivir has shown no mortality benefit (moderate quality evidence) in the treatment of COVID-19. From a cost-benefit perspective, it is our personal opinion that it should not be recommended for use, especially in low and lower middle income countries.
TRIAL REGISTRATION NUMBER
PROSPERO registration number: CRD42020189517.
Topics: Adenosine Monophosphate; Adult; Alanine; Antiviral Agents; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34168031
DOI: 10.1136/bmjopen-2020-048416 -
Journal of Pharmacy & Pharmaceutical... 2021To evaluate the safety and efficacy of remdesivir in adult patients with COVID-19. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the safety and efficacy of remdesivir in adult patients with COVID-19.
METHODS
PubMed, Embase, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, and medRxiv databases were searched using a search strategy tailored to each database. The Consolidated Standards of Reporting Trials (CONSORT) and Strengthening the reporting of observational studies in epidemiology (STROBE) checklists were used for the studies' qualitative assessment. The outcomes studied were mortality, all adverse events, serious adverse events, and clinical improvement. The quantitative synthesis was conducted using fixed and random effects models in the CMA 2.2. Heterogeneity was tested using the I-squared (I2) measure.
RESULTS
In general, six studies, including five randomized controlled trials and one cohort study were found eligible. Comparison of the findings related to both groups receiving remdesivir (10-day remdesivir group) and placebo/control group showed that remdesivir treatment had no significant effect on mortality at day 14 of the treatment (RR=0.769; 95% CI :0.563-1.050; p=0.098), and all adverse events (RR= 1.078; 95% CI: 0.908-1.279; p= 0.392). However, remdesivir had a significant effect on clinical improvement at day 14 compared to placebo/control (OR= 1.447; 95% CI: 1.005-2.085; p= 0.047) and reduced serious adverse events (RR= 0.736; 95% CI: 0.611-0.887; p= 0.001).
CONCLUSION
Remdesivir has positive effects on clinical improvement, and reduction of the risk of serious adverse events. However, it does not influence the mortality at day 14 of treatment.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; COVID-19; Humans; Hypoalbuminemia; Hypokalemia; Randomized Controlled Trials as Topic; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34048669
DOI: 10.18433/jpps31870