Dataset Information

Corticosteroid therapy for critically ill patients with COVID-19: A structured summary of a study protocol for a prospective meta-analysis of randomized trials.

ABSTRACT:

Objectives

Primary objective: To estimate the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization. Secondary objectives: To examine whether the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization varies between subgroups related to treatment characteristics, disease severity at the time of randomization, patient characteristics, or risk of bias. To examine the effect of corticosteroids compared with usual care or placebo on serious adverse events.

Study design

Prospective meta-analysis of randomized controlled trials. Both placebo-controlled and open-label trials are eligible.

Participants

Hospitalised, critically ill patients with suspected or confirmed COVID-19.

Intervention and comparator

Intervention groups will have received therapeutic doses of a steroid (dexamethasone, hydrocortisone or methylprednisolone) with IV or oral administration immediately after randomization. The comparator groups will have received standard of care or usual care or placebo.

Main outcome

All-cause mortality up to 28 days after randomization.

Search methods

Systematic searching of clinicaltrials.gov , EudraCT, the WHO ISRCTN registry, and the Chinese clinical trials registry. Additionally, research and WHO networks will be asked for relevant trials.

Risk of bias assessments

These will be based on the Cochrane RoB 2 tool, and will use structured information provided by the trial investigators on a form designed for this prospective meta-analysis. We will use GRADE to assess the certainty of the evidence.

Statistical analyses

Trial investigators will provide data on the numbers of participants who did and did not experience each outcome according to intervention group, overall and in specified subgroups. We will conduct fixed-effect (primary analysis) and random-effects (Paule-Mandel estimate of heterogeneity and Hartung-Knapp adjustment) meta-analyses. We will quantify inconsistency in effects between trials using I² statistics. Evidence for subgroup effects will be quantified by ratios of odds ratios comparing effects in the subgroups, and corresponding interaction p-values. Comparisons between subgroups defined by trial characteristics will be made using random-effects meta-regression. Comparisons between subgroups defined by patient characteristics will be made by estimating trial-specific ratios of odds ratios comparing intervention effects between subgroups then combining these using random-effects meta-analysis. Steroid interventions will be classified as high or low dose according to whether the dose is greater or less than or equal to 400 mg hydrocortisone per day or equivalent. We will use network meta-analysis methods to make comparisons between the effects of high and low dose steroid interventions (because one trial randomized participants to both low and high dose steroid arms).

Prospero registration number

CRD42020197242 FULL PROTOCOL: The full protocol for this prospective meta-analysis is attached as an additional file, accessible from the Trials website (Additional file 1). To expedite dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol for the systematic review.

SUBMITTER: Sterne JAC

PROVIDER: S-EPMC7443535 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveConservative oxygen strategy is recommended in acute illness while its benefit in ICU patients remains controversial. Therefore, we sought to conduct a systematic review and meta-analysis to examine such oxygen strategies' effect and safety in ICU patients.MethodsWe searched PubMed, Embase, and the Cochrane database from inception to Feb 15, 2021. Randomized controlled trials (RCTs) that compared a conservative oxygen strategy to a conventional strategy in critically ill patients were included. Results were expressed as mean difference (MD) and risk ratio (RR) with a 95% confidence interval (CI). The primary outcome was the longest follow-up mortality. Heterogeneity, sensitivity analysis, and publication bias were also investigated to test the robustness of the primary outcome.ResultsWe included seven trials with a total of 5265 patients. In general, the conventional group had significantly higher SpO2 or PaO2 than that in the conservative group. No statistically significant differences were found in the longest follow-up mortality (RR, 1.03; 95% CI, 0.97-1.10; I2=18%; P=0.34) between the two oxygen strategies when pooling studies enrolling subjects with various degrees of hypoxemia. Further sensitivity analysis showed that ICU patients with mild-to-moderate hypoxemia (PaO2/FiO2 >100 mmHg) had significantly lower mortality (RR, 1.24; 95% CI, 1.05-1.46; I2=0%; P=0.01) when receiving conservative oxygen therapy. These findings were also confirmed in other study periods. Additional, secondary outcomes of the duration of mechanical ventilation, the length of stay in the ICU and hospital, change in sequential organ failure assessment score, and adverse events were comparable between the two strategies.ConclusionsOur findings indicate that conservative oxygen therapy strategy did not improve the prognosis of the overall ICU patients. The subgroup of ICU patients with mild to moderate hypoxemia might obtain prognosis benefit from such a strategy without affecting other critical clinical results.

Project description:BackgroundCorticoid therapy has been recommended in the treatment of critically ill patients with COVID-19, yet its efficacy is currently still under evaluation. We investigated the effect of corticosteroid treatment on 90-day mortality and SARS-CoV-2 RNA clearance in severe patients with COVID-19.Methods294 critically ill patients with COVID-19 were recruited between December 30, 2019 and February 19, 2020. Logistic regression, Cox proportional-hazards model and marginal structural modeling (MSM) were applied to evaluate the associations between corticosteroid use and corresponding outcome variables.ResultsOut of the 294 critically ill patients affected by COVID-19, 183 (62.2%) received corticosteroids, with methylprednisolone as the most frequently administered corticosteroid (175 accounting for 96%). Of those treated with corticosteroids, 69.4% received corticosteroid prior to ICU admission. When adjustments and subgroup analysis were not performed, no significant associations between corticosteroids use and 90-day mortality or SARS-CoV-2 RNA clearance were found. However, when stratified analysis based on corticosteroid initiation time was performed, there was a significant correlation between corticosteroid use (≤ 3 day after ICU admission) and 90-day mortality (logistic regression adjusted for baseline: OR 4.49, 95% CI 1.17-17.25, p = 0.025; Cox adjusted for baseline and time varying variables: HR 3.89, 95% CI 1.94-7.82, p < 0.001; MSM adjusted for baseline and time-dependent variants: OR 2.32, 95% CI 1.16-4.65, p = 0.017). No association was found between corticosteroid use and SARS-CoV-2 RNA clearance even after stratification by initiation time of corticosteroids and adjustments for confounding factors (corticosteroids use ≤ 3 days initiation vs no corticosteroids use) using MSM were performed.ConclusionsEarly initiation of corticosteroid use (≤ 3 days after ICU admission) was associated with an increased 90-day mortality. Early use of methylprednisolone in the ICU is therefore not recommended in patients with severe COVID-19.

Project description:IntroductionGlutamine supplementation is supposed to reduce mortality and nosocomial infections in critically ill patients. However, the recently published reducing deaths due to oxidative stress (REDOX) trials did not provide evidence supporting this. This study investigated the impact of glutamine-supplemented nutrition on the outcomes of critically ill patients using a meta-analysis.MethodsWe searched for and gathered data from the Cochrane Central Register of Controlled Trials, MEDLINE, Elsevier, Web of Science and ClinicalTrials.gov databases reporting the effects of glutamine supplementation on outcomes in critically ill patients. We produced subgroup analyses of the trials according to specific patient populations, modes of nutrition and glutamine dosages.ResultsAmong 823 related articles, eighteen Randomized Controlled Trials (RCTs) met all inclusion criteria. Mortality events among 3,383 patients were reported in 17 RCTs. Mortality showed no significant difference between glutamine group and control group. In the high dosage subgroup (above 0.5 g/kg/d), the mortality rate in the glutamine group was significantly higher than that of the control group (relative risk (RR) 1.18; 95% confidence interval (CI), 1.02 to 1.38; P = 0.03). In 15 trials, which included a total of 2,862 patients, glutamine supplementation reportedly affected the incidence of nosocomial infections in the critically ill patients observed. The incidence of nosocomial infections in the glutamine group was significantly lower than that of the control group (RR 0.85; 95% CI, 0.74 to 0.97; P = 0.02). In the surgical ICU subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.70; 95% CI, 0.52 to 0.94; P = 0.04). In the parental nutrition subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.83; 95% CI, 0.70 to 0.98; P = 0.03). The length of hospital stay was reported in 14 trials, in which a total of 2,777 patients were enrolled; however, the patient length of stay was not affected by glutamine supplementation.ConclusionsGlutamine supplementation conferred no overall mortality and length of hospital stay benefit in critically ill patients. However, this therapy reduced nosocomial infections among critically ill patients, which differed according to patient populations, modes of nutrition and glutamine dosages.