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Title: Azithromycin during Acute Chronic Obstructive Pulmonary Disease Exacerbations Requiring Hospitalization (BACE) A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial
Authors: Vermeersch, Kristina
Gabrovska, Maria
AUMANN, Joseph 
Demedts, Ingel K.
Corhay, Jean-Louis
Marchand, Eric
Slabbynck, Hans
Haenebalcke, Christel
Haerens, Michiel
Hanon, Shane
Jordens, Paul
Peche, Rudi
Fremault, Antoine
Lauwerier, Tine
Delporte, Anja
Vandenberk, Bert
Willems, Rik
Everaerts, Stephanie
Belmans, Ann
Verleden, Geert M.
Troosters, Thierry
Ninane, Vincent
Brusselle, Guy G.
Janssens, Wim
Vincken, Walter
Debrock, Alix
Lamont, Jan
Tits, Geert
Delobbe, Alain
Martinot, Jean-Benoit
Issue Date: 2019
Abstract: Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of an AECOPD requiring 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 an AECOPD and had a smoking history of pack >= 10 years 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 the TF 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, 073; 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.
Notes: [Vermeersch, Kristina; Everaerts, Stephanie; Verleden, Geert M.; Troosters, Thierry; Janssens, Wim] Katholieke Univ Leuven, Lab Resp Dis, Dept Chron Dis Metab & Ageing, Leuven, Belgium. [Belmans, Ann; Bogaerts, Kris] Katholieke Univ Leuven, I BioStat, Leuven, Belgium. [Troosters, Thierry] Katholieke Univ Leuven, Dept Rehabil Sci, Fac Kinesiol & Rehabil Sci, Leuven, Belgium. [Vermeersch, Kristina; Everaerts, Stephanie; Verleden, Geert M.; Janssens, Wim] Univ Hosp Leuven, Dept Resp Dis, Leuven, Belgium. [Vandenberk, Bert; Willems, Rik] Univ Hosp Leuven, Dept Cardiol, Leuven, Belgium. [Gabrovska, Maria; Ninane, Vincent] Univ Libre Bruxelles, Ctr Hosp Univ St Pierre, Dept Pneumol, Brussels, Belgium. [Aumann, Joseph] Jessa Ziekenhuis, Dept Pneumol, Hasselt, Belgium. [Demedts, Ingel K.] AZ Delta Roeselare Menen, Dept Resp Med, Roeselare, Belgium. [Corhay, Jean-Louis] Ctr Hosp Univ, Dept Pneumol, Liege, Belgium. [Marchand, Eric] CHU UCL Namur, Dept Pneumol, Yvoir, Belgium. [Marchand, Eric] Univ Namur, Lab Resp Physiol, Fac Med, NARILIS, Namur, Belgium. [Slabbynck, Hans] ZNA Middelhe, Dept Resp Med, Antwerp, Belgium. [Haenebalcke, Christel] Acad Hosp St Jan, Dept Pneumol, Brugge Oostende, Belgium. [Haerens, Michiel] AZ Groeninge, Dept Pneumol, Kortrijk, Belgium. [Hanon, Shane] UZ Brussel, Dept Pneumol, Jette, Belgium. [Jordens, Paul] Onze Lieve Vrouw Hosp, Dept Pneumol, Aalst, Belgium. [Peche, Rudi] Ctr Hosp Univ Charleroi, Dept Pneumol, Charleroi, Belgium. [Fremault, Antoine] Grand Hop Charleroi, Dept Pneumol, Charleroi, Belgium. [Lauwerier, Tine] Imelda Ziekenhuis, Dept Pneumol, Bonheiden, Belgium. [Delporte, Anja; Brusselle, Guy G.] Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium. [Belmans, Ann; Bogaerts, Kris] Univ Hasselt, Hasselt, Belgium. [Ninane, Vincent] CHU St Pierre, Brussels, Belgium. [Aumann, Joseph] Jessa Ziekenhuis, Hasselt, Belgium. [Demedts, Ingel K.] AZ Delta, Roeselare Menen, Belgium. [Slabbynck, Hans] ZNA Middelheim, Antwerp, Belgium. [Marchand, Eric] CHU UCL Namur, Yvoir, Belgium. [Haenebalcke, Christel] AZ St Jan Ziekenhuis, Brugge, Belgium. [Peche, Rudi] CHU Charleroi, Charleroi, Belgium. [Brusselle, Guy G.] UZ Gent, Ghent, Belgium. [Vincken, Walter] UZ Brussel, Brussels, Belgium. [Corhay, Jean-Louis] CHU Liege, Luik, Belgium. [Haerens, Michiel] AZ Groeninge, Kortrijk, Belgium. [Fremault, Antoine] Grand Hop Charleroi, Charleroi, Belgium. [Lauwerier, Tine] Imelda Ziekenhuis, Bonheiden, Belgium. [Debrock, Alix] St Augustinus Ziekenhuis, Antwerp, Belgium. [Lamont, Jan] Maria Middelares Ziekenhuis, Ghent, Belgium. [Tits, Geert] St Andriesziekenhuis, Tielt, Belgium. [Jordens, Paul] Onze Lieve Vrouw Hosp, Aalst, Belgium. [Delobbe, Alain] Clin Reine Astrid, Malmedy, Belgium. [Martinot, Jean-Benoit] Clin Ste Elisabeth, Namur, Belgium.
Keywords: macrolide; composite; time to event; treatment failure; readmission;macrolide; composite; time to event; treatment failure; readmission
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ISSN: 1073-449X
e-ISSN: 1535-4970
DOI: 10.1164/rccm.201901-0094OC
ISI #: 000488777100015
Category: A1
Type: Journal Contribution
Validations: ecoom 2020
Appears in Collections:Research publications

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