Azithromycin during acute chronic obstructive pulmonary disease exacerbations requiring hospitalization (BACE) a multicenter, randomized, double-blind, placebo-controlled trial

Kristina Vermeersch, Maria Gabrovska, Joseph Aumann, Ingel K. Demedts, Jean Louis Corhay, Eric Marchand, Hans Slabbynck, Christel Haenebalcke, Michiel Haerens, Shane Hanon, Paul Jordens, Rudi Peché, Antoine Fremault, Tine Lauwerier, Anja Delporte, Bert Vandenberk, Rik Willems, Stephanie Everaerts, Ann Belmans, Kris BogaertsGeert M. Verleden, Thierry Troosters, Vincent Ninane, Guy G. Brusselle, Wim Janssens

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)857-868
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume200
Issue number7
DOIs
Publication statusPublished - 1 Oct 2019

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Azithromycin
Chronic Obstructive Pulmonary Disease
Disease Progression
Hospitalization
Placebos
Treatment Failure
Adrenal Cortex Hormones
Anti-Bacterial Agents
Therapeutics
Mortality
Hospital Mortality
Smoking
Research Personnel
Confidence Intervals
Pharmaceutical Preparations
Population

Keywords

  • Composite
  • Macrolide
  • Readmission
  • Time to event
  • Treatment failure

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Vermeersch, Kristina ; Gabrovska, Maria ; Aumann, Joseph ; Demedts, Ingel K. ; Corhay, Jean Louis ; Marchand, Eric ; Slabbynck, Hans ; Haenebalcke, Christel ; Haerens, Michiel ; Hanon, Shane ; Jordens, Paul ; Peché, Rudi ; Fremault, Antoine ; Lauwerier, Tine ; Delporte, Anja ; Vandenberk, Bert ; Willems, Rik ; Everaerts, Stephanie ; Belmans, Ann ; Bogaerts, Kris ; Verleden, Geert M. ; Troosters, Thierry ; Ninane, Vincent ; Brusselle, Guy G. ; Janssens, Wim. / Azithromycin during acute chronic obstructive pulmonary disease exacerbations requiring hospitalization (BACE) a multicenter, randomized, double-blind, placebo-controlled trial. In: American Journal of Respiratory and Critical Care Medicine. 2019 ; Vol. 200, No. 7. pp. 857-868.
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abstract = "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.",
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author = "Kristina Vermeersch and Maria Gabrovska and Joseph Aumann and Demedts, {Ingel K.} and Corhay, {Jean Louis} and Eric Marchand and Hans Slabbynck and Christel Haenebalcke and Michiel Haerens and Shane Hanon and Paul Jordens and Rudi Pech{\'e} and Antoine Fremault and Tine Lauwerier and Anja Delporte and Bert Vandenberk and Rik Willems and Stephanie Everaerts and Ann Belmans and Kris Bogaerts and Verleden, {Geert M.} and Thierry Troosters and Vincent Ninane and Brusselle, {Guy G.} and Wim Janssens",
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Vermeersch, K, Gabrovska, M, Aumann, J, Demedts, IK, Corhay, JL, Marchand, E, Slabbynck, H, Haenebalcke, C, Haerens, M, Hanon, S, Jordens, P, Peché, R, Fremault, A, Lauwerier, T, Delporte, A, Vandenberk, B, Willems, R, Everaerts, S, Belmans, A, Bogaerts, K, Verleden, GM, Troosters, T, Ninane, V, Brusselle, GG & Janssens, W 2019, 'Azithromycin during acute chronic obstructive pulmonary disease exacerbations requiring hospitalization (BACE) a multicenter, randomized, double-blind, placebo-controlled trial', American Journal of Respiratory and Critical Care Medicine, vol. 200, no. 7, pp. 857-868. https://doi.org/10.1164/rccm.201901-0094OC

Azithromycin during acute chronic obstructive pulmonary disease exacerbations requiring hospitalization (BACE) a multicenter, randomized, double-blind, placebo-controlled trial. / Vermeersch, Kristina; Gabrovska, Maria; Aumann, Joseph; Demedts, Ingel K.; Corhay, Jean Louis; Marchand, Eric; Slabbynck, Hans; Haenebalcke, Christel; Haerens, Michiel; Hanon, Shane; Jordens, Paul; Peché, Rudi; Fremault, Antoine; Lauwerier, Tine; Delporte, Anja; Vandenberk, Bert; Willems, Rik; Everaerts, Stephanie; Belmans, Ann; Bogaerts, Kris; Verleden, Geert M.; Troosters, Thierry; Ninane, Vincent; Brusselle, Guy G.; Janssens, Wim.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 200, No. 7, 01.10.2019, p. 857-868.

Research output: Contribution to journalArticle

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

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

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