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Comparison of the Clinical Outcomes Between Nebulized and Systemic Corticosteroids in the Treatment of Acute Exacerbation of COPD in China (CONTAIN Study): A Post Hoc Analysis.

ABSTRACT: Background and Objective:Although corticosteroids have been widely used in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), few studies have evaluated the effectiveness of nebulized corticosteroids (NCS), systemic corticosteroids (SCS), and NCS plus SCS in the management of AECOPD in China. This study aimed to evaluate the effectiveness of NCS, SCS, and NCS plus SCS in Chinese patients with AECOPD. Patients and Methods:This was a real-world study of AECOPD patients at 43 sites from January to September 2014. During hospitalization, patients treated with nebulized budesonide (NCS group, n=1091), SCS (SCS group, n=709), or both (NCS+SCS group, n=1846) were included. Propensity score matching (PSM) and subgroup analyses were performed. The primary outcomes were the length of hospital stay, mortality, and change in arterial blood gases from baseline. Results:Multivariable analysis showed that the three treatments at the same severity of AECOPD were not significantly different regarding intubation rates, rates of pneumonia improvement at discharge, rates of new-onset pneumonia in hospital, and mortality. Following PSM, NCS+SCS was associated with greater length of hospital stay than both NCS and SCS (in patients without respiratory failure [RF, P<0.001] and with type I RF [P=0.022]), and more hospitalization costs than the other two treatments (in patients without RF [P<0.001]). Conclusion:NCS is effective for patients with AECOPD, which may be an alternative treatment option. Further clinical trials are urgently needed to better understand the efficacy of NCS, SCS, and NCS+SCS in AECOPD management in China.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7533224 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comparison of the Clinical Outcomes Between Nebulized and Systemic Corticosteroids in the Treatment of Acute Exacerbation of COPD in China (CONTAIN Study): A Post Hoc Analysis.

Chen Yahong Y Liu Yang Y Zhang Jing J Yao Wanzhen W Yang Jingping J Li Fan F Lu Liwen L Zheng Jinping J Han Xiaowen X Xu Jin-Fu JF

International journal of chronic obstructive pulmonary disease 20200930

<h4>Background and objective</h4>Although corticosteroids have been widely used in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), few studies have evaluated the effectiveness of nebulized corticosteroids (NCS), systemic corticosteroids (SCS), and NCS plus SCS in the management of AECOPD in China. This study aimed to evaluate the effectiveness of NCS, SCS, and NCS plus SCS in Chinese patients with AECOPD.<h4>Patients and methods</h4>This was a real-world st ...[more]

PMID: 33061352

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Project description:BackgroundRevefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 s (FEV1) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD.MethodsA post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV1, St. George's Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV1 30%-< 50% and < 30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥ 12% and ≥ 200 mL increase in FEV1) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (> 65 and > 75 years), and comorbidity risk factors.ResultsRevefenacin demonstrated significant improvements in FEV1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio > 2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio > 2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged > 75 years.ConclusionsRevefenacin showed significantly greater improvements in FEV1 versus placebo in the ITT population and all subgroups. Furthermore, there were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Based on the data presented, revefenacin could be a therapeutic option among patients with markers of more severe COPD.Trial registrationClinical trials registered with www.clinicaltrials.gov (Studies 0126 [NCT02459080; prospectively registered 22 May 2015] and 0127 [NCT02512510; prospectively registered 28 July 2015]).

Project description:Objective: Systematic comparison of the efficacy and safety of nebulized corticosteroids and systemic corticosteroids for treating acute exacerbation of chronic obstructive pulmonary disease reported by high-quality, real-world observational studies and randomized controlled trials. Methods: MEDLINE, EMBASE, and Cochrane Library databases were searched from the database creation date to 1 April 2022. Eligible observational studies and randomized controlled trials with changes in lung function and blood gas analysis results as the primary endpoints of interest, and the numbers of deteriorations and adverse events as the secondary endpoints were sought. Results: Of the 2,837 identified studies, 22 were eligible and included in our analysis (N = 5,764 patients). Compared with systemic corticosteroids, nebulized corticosteroids resulted in comparable improvements in predicted FEV1%, FEV1, PaO2, PaCO2, and SaO2 at the treatment endpoint; however, observational studies reported more significant treatment outcomes with nebulized corticosteroids for FEV1 [mean difference, 0.26; 95% confidence interval (CI), 0.17-0.35; p < 0.005]. In terms of adverse reactions, the risks of gastrointestinal symptoms were 11% [Log risk ratio (LogRR) = 0.10; 95% confidence interval, 0.05-0.15; p < 0.005] higher for systemic corticosteroids than for nebulized corticosteroids in randomized controlled trials, while the risks of hyperglycemia were 6% (LogRR = 0.06; 95% CI, 0.01-0.11; p = 0.01) and 13% (LogRR = 0.12; 95% CI, 0.09-0.16; p < 0.005) higher in observational studies and randomized controlled trials, respectively. Conclusion: According to our meta-analysis, either study type supported that nebulized corticosteroids can be used as an alternative to systemic corticosteroids for treating acute exacerbation of the chronic obstructive pulmonary disease. However, more well-designed prospective studies are needed to determine the optimal dose of nebulized corticosteroids and the advantages of sequential therapy.

Project description:BackgroundChronic obstructive pulmonary disease (COPD) clinical trials aimed at evaluating treatment effects on exacerbations often suffer from early discontinuations of randomized treatment. Treatment discontinuations imply a loss of information and should ideally be considered in the statistical analysis of trial results, particularly if the discontinuations are related to the disease or treatment itself. Here, we explore this issue by investigating (1) whether there exists an association between the risks of exacerbation and treatment discontinuation in COPD clinical trials and (2) whether disregarding this association can cause bias in exacerbation treatment effect estimates. We focus on the hypothetical estimand, i.e. the treatment effect that would have been observed had all subjects completed the trial as planned.MethodsThe association between exacerbation and discontinuation risks was analysed by applying a joint frailty (random effect) model - allowing for the simultaneous analysis of multiple types of correlated events - to data from five Phase III-IV COPD clinical trials. Specifically, the impact of the association on exacerbation treatment effect estimates was assessed by comparing the treatment hazard ratios of the joint frailty model to the rate/hazard ratios of two related statistical models (the negative binomial and shared frailty models), which both assume discontinuations to be unrelated to the trial outcome. The models were also compared using simulated data.ResultsA statistically significant (p < 0.0001), positive association between exacerbation and discontinuation risks was found in all trials. Importantly, simulations confirmed that - with such an association - models disregarding the association risk producing biased results (> 5 percentage point difference in hazard/rate ratio). For some treatment comparisons in the clinical trials, the difference in treatment effect estimates between the joint frailty and the other models was as high as 10-15 percentage points. The difference was affected by the strength of the exacerbation-discontinuation association, the population heterogeneity in exacerbation risk, and the difference in discontinuation rates between treatment arms.ConclusionsWe have identified an association between the risks of exacerbation and treatment discontinuation in five COPD clinical trials. We recommend using the joint frailty model to account for this association when estimating exacerbation treatment effects, particularly when targeting the hypothetical estimand.

Project description:Purpose Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a leading cause of deterioration in patients with otherwise stably controlled COPD. Treatments of AECOPD often require the use of corticosteroid therapy in conjunction with bronchodilators and antibiotics. However, the duration and dosage of corticosteroids still remain unclear. We propose to perform this systematic review and meta-analysis of all available randomized control trials (RCTs) and observational cohort studies to comprehensively assess the efficacy and safety of different corticosteroid duration and dosing regimen in the current body of evidence. Methods We will search MEDLINE, EMBASE, CENTRAL via Ovid as well as CINAHL and Web of Science for available literature comparing different corticosteroid duration and dosage in the treatment of AECOPD. We will perform title and full text screening in duplicate, then extract relevant data using a pre-piloted extraction form. We will define short duration as less than 14-day duration of treatment and long duration as greater than 14-day treatment. We will report mortality difference as our primary outcome, with additional comparisons in incidence of re-exacerbation, hospital length of stay, lung function, incidence of hyperglycemia and infection. We will perform risk of bias assessment using the ROB2.0 and ROBINS-I tool, as well as the GRADE assessment to assess the quality of evidence. Results We will publish the full results of our systematic review and meta-analysis in a peer-reviewed journal. Discussions To our knowledge, this represents an updated and most comprehensive review of the literature comparing different duration and dosing regimen of corticosteroid treatments in AECOPD, as we will include both RCTs and observational studies without date or language restrictions. We aim to validate prior meta-analyses and study findings on the efficacy of short duration corticosteroid therapy over longer treatments and to inform future research directions in dosing regimens.

Project description:PurposeUsing a composite endpoint, pooled data from two 12-week Phase III placebo-controlled trials (GOLDEN 3, NCT02347761; GOLDEN 4, NCT02347774) were analyzed to determine whether glycopyrrolate inhalation solution (25 mcg and 50 mcg) administered twice daily (BID) via the eFlow® Closed System nebulizer (GLY) reduced the risk of clinically important deterioration (CID) in patients with moderate-to-very-severe COPD.MethodsCID was defined as ≥100-mL decrease from baseline in post-bronchodilator trough forced expiratory volume in one second (FEV1), or ≥4-unit increase in baseline St. George's Respiratory Questionnaire (SGRQ) total score, or moderate/severe exacerbation. The relative treatment effect of GLY versus placebo on the odds of CID (any and by component endpoints) was expressed as the odds ratio (OR) and 95% confidence interval (CI). Subgroups categorized by age (<65/≥65 years), sex, smoking status (current/former), long-acting beta agonist (LABA) use, FEV1 (<50%/≥50%), and peak inspiratory flow rate (PIFR) (<60 L/min/≥60 L/min) were analyzed.ResultsCompared to placebo, GLY 25 mcg and 50 mcg BID over 12 weeks significantly reduced the risk of CID by 50% (OR: 0.50 [0.37-0.68]) and 40% (OR: 0.60 [0.44-0.80]), respectively. Subjects treated with GLY 25 mcg BID were 59% less likely to experience CID in FEV1 (OR: 0.41 [0.27-0.62]) and 48% less likely to perceive CID in health status (OR: 0.52 [0.37-0.73]). Statistically significant reductions were also observed at the higher dose. The incidence of moderate/severe exacerbations was low and comparable among the cohorts. GLY 25 mcg BID was significantly more effective than placebo (p<0.05) in preventing CID irrespective of age, smoking status, LABA use, COPD severity, or PIFR. Subjects <65 years (OR 0.45 [0.29-0.68]) and those with PIFR <60 L/min (OR 0.36 [0.20-0.67]) exhibited the largest benefit.ConclusionNebulized GLY over 12 weeks significantly reduced the risk of CID and provided greater short-term stability in patients with moderate-to-very-severe COPD.

Project description:ImportanceAlthough professional society guidelines discourage use of empirical antibiotics in the treatment of asthma exacerbation, high antibiotic prescribing rates have been recorded in the United States and elsewhere.ObjectiveTo determine the association of antibiotic treatment with outcomes among patients hospitalized for asthma and treated with corticosteroids.Design, setting, and participantsRetrospective cohort study of data of 19 811 adults hospitalized for asthma exacerbation and treated with systemic corticosteroids in 542 US acute care hospitals from January 1, 2015, through December 31, 2016.ExposuresEarly antibiotic treatment, defined as an treatment with an antibiotic initiated during the first 2 days of hospitalization and prescribed for a minimum of 2 days.Main outcomes and measuresThe primary outcome measure was hospital length of stay. Other measures were treatment failure (initiation of mechanical ventilation, transfer to the intensive care unit after hospital day 2, in-hospital mortality, or readmission for asthma) within 30 days of discharge, hospital costs, and antibiotic-related diarrhea. Multivariable adjustment, propensity score matching, propensity weighting, and instrumental variable analysis were used to assess the association of antibiotic treatment with outcomes.ResultsOf the 19 811 patients, the median (interquartile range [IQR]) age was 46 (34-59) years, 14 389 (72.6%) were women, 8771 (44.3%) were white, and Medicare was the primary form of health insurance for 5120 (25.8%). Antibiotics were prescribed for 8788 patients (44.4%). Compared with patients not treated with antibiotics, treated patients were older (median [IQR] age, 48 [36-61] vs 45 [32-57] years), more likely to be white (48.6% vs 40.9%) and smokers (6.6% vs 5.3%), and had a higher number of comorbidities (eg, congestive heart failure, 6.2% vs 5.8%). Those treated with antibiotics had a significantly longer hospital stay (median [IQR], 4 [3-5] vs 3 [2-4] days) and a similar rate of treatment failure (5.4% vs 5.8%). In propensity score-matched analysis, receipt of antibiotics was associated with a 29% longer hospital stay (length of stay ratio, 1.29; 95% CI, 1.27-1.31) and higher cost of hospitalization (median [IQR] cost, $4776 [$3219-$7373] vs $3641 [$2346-$5942]) but with no difference in the risk of treatment failure (propensity score-matched OR, 0.95; 95% CI, 0.82-1.11). Multivariable adjustment, propensity score weighting, and instrumental variable analysis as well as several sensitivity analyses yielded similar results.Conclusions and relevanceAntibiotic therapy may be associated with a longer hospital length of stay, higher hospital cost, and similar risk of treatment failure. These results highlight the need to reduce inappropriate antibiotic prescribing among patients hospitalized for asthma.

Dataset Information

Comparison of the Clinical Outcomes Between Nebulized and Systemic Corticosteroids in the Treatment of Acute Exacerbation of COPD in China (CONTAIN Study): A Post Hoc Analysis.

Publications

Comparison of the Clinical Outcomes Between Nebulized and Systemic Corticosteroids in the Treatment of Acute Exacerbation of COPD in China (CONTAIN Study): A Post Hoc Analysis.

Similar Datasets

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