Kristina Vermeersch1,2, Maria Gabrovska3, Joseph Aumann4, Ingel K Demedts5, Jean-Louis Corhay6, Eric Marchand7,8, Hans Slabbynck9, Christel Haenebalcke10, Michiel Haerens11, Shane Hanon12, Paul Jordens13, Rudi Peché14, Antoine Fremault15, Tine Lauwerier16, Anja Delporte17, Bert Vandenberk18, Rik Willems18, Stephanie Everaerts1,2, Ann Belmans19,20, Kris Bogaerts19,20, Geert M Verleden1,2, Thierry Troosters1,21, Vincent Ninane3, Guy G Brusselle17, Wim Janssens1,2. 1. Laboratory of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing. 2. Department of Respiratory Diseases and. 3. Department of Pneumology, Centre Hospitalier Universitaire Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium. 4. Department of Pneumology, Jessa Ziekenhuis, Hasselt, Belgium. 5. Department of Respiratory Medicine, AZ Delta Roeselare-Menen, Roeselare, Belgium. 6. Department of Pneumology, Centre Hospitalier Universitaire, Liège, Belgium. 7. Department of Pneumology, CHU-UCL-Namur, Yvoir, Belgium. 8. Faculty of Medicine, NARILIS, Laboratory of Respiratory Physiology, University of Namur, Namur, Belgium. 9. Department of Respiratory Medicine, ZNA Middelheim, Antwerpen, Belgium. 10. Department of Pneumology, AZ Sint-Jan, Brugge-Oostende, Belgium. 11. Department of Pneumology, AZ Groeninge, Kortrijk, Belgium. 12. Department of Pneumology, UZ Brussel, Jette, Belgium. 13. Department of Pneumology, Onze-Lieve-Vrouw Ziekenhuis, Aalst, Belgium. 14. Department of Pneumology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium. 15. Department of Pneumology, Grand Hôpital de Charleroi, Charleroi, Belgium. 16. Department of Pneumology, Imelda Ziekenhuis, Bonheiden, Belgium. 17. Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; and. 18. Department of Cardiology, University Hospitals Leuven, Leuven, Belgium. 19. I-BioStat, and. 20. Universiteit Hasselt, Hasselt, Belgium. 21. Department of Rehabilitation Sciences, Faculty of Kinesiology and Rehabilitation Sciences, KU Leuven, Leuven, Belgium.
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 ≥10 pack-years and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission toazithromycin 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 all-cause 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.
RCT Entities:
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 ≥10 pack-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 all-cause 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.
Entities:
Keywords:
composite; macrolide; readmission; time to event; treatment failure
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