TY - JOUR
T1 - Azithromycin during acute chronic obstructive pulmonary disease exacerbations requiring hospitalization (BACE) a multicenter, randomized, double-blind, placebo-controlled trial
AU - Vermeersch, Kristina
AU - Gabrovska, Maria
AU - Aumann, Joseph
AU - Demedts, Ingel K.
AU - Corhay, Jean Louis
AU - Marchand, Eric
AU - Slabbynck, Hans
AU - Haenebalcke, Christel
AU - Haerens, Michiel
AU - Hanon, Shane
AU - Jordens, Paul
AU - Peché, Rudi
AU - Fremault, Antoine
AU - Lauwerier, Tine
AU - Delporte, Anja
AU - Vandenberk, Bert
AU - Willems, Rik
AU - Everaerts, Stephanie
AU - Belmans, Ann
AU - Bogaerts, Kris
AU - Verleden, Geert M.
AU - Troosters, Thierry
AU - Ninane, Vincent
AU - Brusselle, Guy G.
AU - Janssens, Wim
N1 - Funding Information:
Supported by the Flemish Government Agency for Innovation by Science and Technology (IWT) through the “Toegepast Biomedisch onderzoek met een primair Maatschappelijke finaliteit” (TBM) program (grant number IWT-TBM130233). The trial was approved and supported by the Belgian Thoracic Society (BVP-SBP), which provided logistic support for organizing the investigator meetings. Financial support for the study logistics was also received from TEVA, Belgium. The IWT, BVP-SBP, and TEVA were not involved in the study design; the collection, analysis, and interpretation of data; writing of the manuscript; or the decision to submit the manuscript for publication.
Publisher Copyright:
© 2019 by the American Thoracic Society.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of anAECOPDrequiring hospitalization remains to be defined. Objectives: We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care. Methods: In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, patients who had been hospitalized for anAECOPDand had a smoking history of>10 packyears and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission to azithromycin or placebo. The study drug (500 mg/d for 3 d) was administered on top of a standardized acute treatment of systemic corticosteroids and antibiotics, and subsequently continued for 3 months (250 mg/2 d). The patients were followed for 6 months thereafter. Time-to-first-event analyses evaluated theTF rate within 3 months as a novel primary endpoint in the intention-to-treat population, with TF defined as the composite of treatment intensification with systemic corticosteroids and/or antibiotics, a step-up in hospital care or readmission for respiratory reasons, or allcause mortality. Measurements and Main Results: A total of 301 patients were randomized to azithromycin (n = 147) or placebo (n = 154). The TF rate within 3 months was 49% in the azithromycin group and 60% in the placebo group (hazard ratio, 0.73; 95% confidence interval, 0.53-1.01; P = 0.0526). Treatment intensification, step-up in hospital care, and mortality rates within 3 months were 47% versus 60% (P = 0.0272), 13% versus 28% (P=0.0024), and 2% versus 4% (P = 0.5075) in the azithromycin and placebo groups, respectively. Clinical benefits were lost 6 months after withdrawal. Conclusions: Three months of azithromycin for an infectious AECOPD requiring hospitalization may significantly reduce TF during the highest-risk period. Prolonged treatment seems to be necessary to maintain clinical benefits.
AB - Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of anAECOPDrequiring hospitalization remains to be defined. Objectives: We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care. Methods: In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, patients who had been hospitalized for anAECOPDand had a smoking history of>10 packyears and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission to azithromycin or placebo. The study drug (500 mg/d for 3 d) was administered on top of a standardized acute treatment of systemic corticosteroids and antibiotics, and subsequently continued for 3 months (250 mg/2 d). The patients were followed for 6 months thereafter. Time-to-first-event analyses evaluated theTF rate within 3 months as a novel primary endpoint in the intention-to-treat population, with TF defined as the composite of treatment intensification with systemic corticosteroids and/or antibiotics, a step-up in hospital care or readmission for respiratory reasons, or allcause mortality. Measurements and Main Results: A total of 301 patients were randomized to azithromycin (n = 147) or placebo (n = 154). The TF rate within 3 months was 49% in the azithromycin group and 60% in the placebo group (hazard ratio, 0.73; 95% confidence interval, 0.53-1.01; P = 0.0526). Treatment intensification, step-up in hospital care, and mortality rates within 3 months were 47% versus 60% (P = 0.0272), 13% versus 28% (P=0.0024), and 2% versus 4% (P = 0.5075) in the azithromycin and placebo groups, respectively. Clinical benefits were lost 6 months after withdrawal. Conclusions: Three months of azithromycin for an infectious AECOPD requiring hospitalization may significantly reduce TF during the highest-risk period. Prolonged treatment seems to be necessary to maintain clinical benefits.
KW - Composite
KW - Macrolide
KW - Readmission
KW - Time to event
KW - Treatment failure
UR - http://www.scopus.com/inward/record.url?scp=85072621151&partnerID=8YFLogxK
U2 - 10.1164/rccm.201901-0094OC
DO - 10.1164/rccm.201901-0094OC
M3 - Article
C2 - 31046405
AN - SCOPUS:85072621151
SN - 1073-449X
VL - 200
SP - 857
EP - 868
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 7
ER -