The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

Vermeersch, Kristina; Gabrovska, Maria; Deslypere, Griet; Demedts, Ingel K.; Slabbynck, Hans; Aumann, Joseph; Ninane, Vincent; Verleden, Geert M.; Troosters, Thierry; Bogaerts, Kris; Janssens, Wim

doi:10.2147/copd.s95501

Cited by 14 publications

(12 citation statements)

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“…Management strategies that aim to minimise eosinophilic airway inflammation in both asthma and COPD using inhaled steroids have shown to be effective in decreasing exacerbations [5]. Furthermore, selection of patients based on eosinophilia or neutrophilia appears to increase the efficacy of novel biologicals, such as anti-interleukin-5, or macrolide therapy [3,[5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label

et al. 2018

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Asthma and chronic obstructive pulmonary disease (COPD) are complex and overlapping diseases that include inflammatory phenotypes. Novel anti-eosinophilic/anti-neutrophilic strategies demand rapid inflammatory phenotyping, which might be accessible from exhaled breath.Our objective was to capture clinical/inflammatory phenotypes in patients with chronic airway disease using an electronic nose (eNose) in a training and validation set.This was a multicentre cross-sectional study in which exhaled breath from asthma and COPD patients (n=435; training n=321 and validation n=114) was analysed using eNose technology. Data analysis involved signal processing and statistics based on principal component analysis followed by unsupervised cluster analysis and supervised linear regression.Clustering based on eNose resulted in five significant combined asthma and COPD clusters that differed regarding ethnicity (p=0.01), systemic eosinophilia (p=0.02) and neutrophilia (p=0.03), body mass index (p=0.04), exhaled nitric oxide fraction (p<0.01), atopy (p<0.01) and exacerbation rate (p<0.01). Significant regression models were found for the prediction of eosinophilic (R=0.581) and neutrophilic (R=0.409) blood counts based on eNose. Similar clusters and regression results were obtained in the validation set.Phenotyping a combined sample of asthma and COPD patients using eNose provides validated clusters that are not determined by diagnosis, but rather by clinical/inflammatory characteristics. eNose identified systemic neutrophilia and/or eosinophilia in a dose-dependent manner.

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Section: Introductionmentioning

confidence: 99%

Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label

et al. 2018

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“…The retrospective nature of this study may have prevented the detection of differences in long‐term mortality due to macrolide therapies during the hospitalized treatment period or may have impaired our ability to examine the delayed antiinflammatory effects of the macrolides. Ongoing research using macrolides in the acute exacerbation period, followed by chronic therapy during the known high‐risk postexacerbation period, may answer this important question …”

Section: Discussionmentioning

confidence: 99%

“…Ongoing research using macrolides in the acute exacerbation period, followed by chronic therapy during the known high-risk postexacerbation period, may answer this important question. 35 Database limitations are also a consideration when interpreting results. Data were only included through 2014, so the impact of contemporary best practices related to evidence that has emerged since our study period cannot be evaluated.…”

Section: Discussionmentioning

confidence: 99%

Impact of Macrolide Antibiotics on Hospital Readmissions and Other Clinically Important Outcomes in Critically Ill Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Propensity Score–Matched Cohort Study

et al. 2019

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Study Objective To assess whether a macrolide‐based antibiotic treatment strategy reduces in‐hospital mortality, decreases hospital readmissions, or improves other clinically important outcomes compared with a non‐macrolide antibiotic treatment strategy in critically ill patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Design Propensity score–matched pharmacoepidemiologic cohort study. Data Source Premier's Perspective Hospital Database. Patients A total of 28,700 adults aged 40 years or older who were admitted to one of 566 United States intensive care units and had the primary diagnosis of AECOPD between January 2010 and December 2014 and received antibiotic treatment within 2 days of hospital admission were included. Patients were divided into macrolide (11,602 patients [40%]) or non‐macrolide (17,098 patients [60%]) antibiotic treatment groups. Propensity score analysis successfully matched 8660 patients in each treatment group. Measurements and Main Results In the matched cohort, the macrolide treatment group was not associated with decreased hospital mortality after day 2 (3.0% vs 3.3%, p=0.28), intensive care unit length of stay (2 days vs 2 days, p=0.12), hospital length of stay (6 days vs 6 days, p=0.86), or length of assisted ventilation (3 days vs 3 days, p=0.71), compared with the non‐macrolide treatment group. However, a macrolide‐based antibiotic regimen was associated with an overall reduction in 30‐day hospital readmissions (7.3% vs 8.8%, p<0.01), increased time to next all‐cause (159 vs 130 days, p<0.01) or AECOPD (200 vs 175 days, p=0.03) readmission, and decreased hospital costs ($32,730 vs $34,021, p<0.01). Conclusion The results of this study suggest that inclusion of a macrolide antibiotic in the treatment regimen may have both acute and sustained benefits in critically ill patients admitted to the intensive care unit with an AECOPD, including reductions in hospital readmissions and improvements in time to next readmission.

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“…Additional details on the study protocol (NCT02135354) and obtained results are described elsewhere. 7,8 In December 2012, the BACE trial consortium was established consisting of respiratory physicians from 5 academic and 14 non-academic hospitals, with the University Hospital Leuven as lead centre. The protocol was submitted in February 2013 to the program for applied biomedical research (TBM, founded by the Flemish government agency for innovation by science and technology, IWT) and received the maximum funding budget (€1.000.000) and duration (48 months) in June 2013.…”

Section: Bace Trialmentioning

confidence: 99%

Challenges and threats of investigator-initiated multicenter randomized controlled trials: the BACE trial experience

et al. 2019

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Background: Investigator-initiated clinical research has become a complex environment. Increasing administrative tasks and costs, imposed by stringent regulatory demands, risk to reduce this creative, independent and indispensable research field. The objective of the present study was to illustrate the burden of non-scientific challenges associated with an investigator-initiated multicentre randomized controlled trial, based on the Belgian trial with azithromycin for Chronic obstructive pulmonary disease (COPD) Exacerbations requiring hospitalization (BACE) trial experience.Methods: The trial enrolled 301 patients with COPD, hospitalized for an acute exacerbation between 2014-2017, and assessed the potential of azithromycin, an off-patent antibiotic. Key experienced challenges were complemented with registry data from the Clinical Trial Centre of the University Hospital Leuven to outline the local clinical respiratory research field, quotations for the trial protocol obtained from 3 pharmaceutical companies to provide insight into the budget restraints and a participation survey to capture the consortium’s perspective.Results: 60% of the required sample size was enrolled. Key challenges included trial implementation, study drug and database management. Industry-initiated trials dominated the local research field (61%), whereas investigator-initiated prospective interventional and multicenter trials accounted for 19% and 13%, respectively. The triple quotation revealed the BACE trial to require 1.6 to 2.1-fold the amount when executed by the pharmaceutical industry. The survey identified the lack of a local study team as an important obstacle for participation, along with inadequate financial compensation and excessive administrative workload.Conclusions: Without an adaptation of current regulatory and funding policies to overcome non-scientific challenges, investigator-initiated clinical research is risking to further decline.

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The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

Cited by 14 publications

References 40 publications

Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label

Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label

Impact of Macrolide Antibiotics on Hospital Readmissions and Other Clinically Important Outcomes in Critically Ill Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Propensity Score–Matched Cohort Study

Challenges and threats of investigator-initiated multicenter randomized controlled trials: the BACE trial experience

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