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.
BACKGROUND
Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions.


METHODS
Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge.


CONCLUSIONS
We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs.
KU Leuven, Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Faculty of Medicine, Leuven, Belgium.
Kristina
K
Vermeersch
Department of Pneumology, Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium.
Maria
M
Gabrovska
Department of Pneumology, Jessa Ziekenhuis, Hasselt, Belgium.
Griet
G
Deslypere
Department of Respiratory Medicine, AZ Delta Roeselare-Menen, Roeselare, Belgium.
Ingel K
IK
Demedts
Department of Respiratory Medicine, ZNA Middelheim, Antwerpen, Belgium.
Hans
H
Slabbynck
Department of Pneumology, Jessa Ziekenhuis, Hasselt, Belgium.
Joseph
J
Aumann
Department of Pneumology, Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium.
Vincent
V
Ninane
KU Leuven, Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Faculty of Medicine, Leuven, Belgium.
Geert M
GM
Verleden
KU Leuven, Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Faculty of Medicine, Leuven, Belgium; KU Leuven, Department of Rehabilitation Sciences, Faculty of Kinesiology and Rehabilitation Sciences, Leuven, Belgium.
Thierry
T
Troosters
KU Leuven, Department of Public Health and Primary Care, I-BioStat, Leuven, Belgium; Hasselt University, Hasselt, Belgium.
Kris
K
Bogaerts
Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Guy G
GG
Brusselle
KU Leuven, Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Faculty of Medicine, Leuven, Belgium.
Wim
W
Janssens
D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D006760:Hospitalization; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012107:Research Design
D000900:Anti-Bacterial Agents; D017963:Azithromycin
COPD; RCT; acute exacerbation; azithromycin; macrolide antibiotics; physical activity