Randomized double blind placebo-controlled study to demonstrate that antibiotics are not needed in moderate acute exacerbations of COPD - Results from the ABACOPD study

Abstract

<b>Background:</b> The role of antibiotic treatment in acute moderate exacerbations of COPD (AE-COPD) is still debated. <b>Design:</b> Double-blind randomized placebo-controlled multi-center clinical trial to demonstrate that placebo is non-inferior to Sultamicillin in hospitalized AECOPD patients regarding the proportion of treatment failures (patients in need of additional antibiotic therapy during the treatment period or until the test of cure visit (day 30)). <b>Results:</b> The treatment failure rate as defined for the primary analysis was lower in the Sultamicillin group (23/150=15.3%) than in the Placebo-group (36/144=25.0%). The Mantel-Haenszel-Estimate (stratified for center) for the risk difference (Placebo – Sultamicillin) in the ITT population with the most conservative strategy to replace missing values is 9.97%, 95% confidence interval (CI) [0.7%; 19.23%]. Thus, non-inferiority of placebo to Sultamicillin could not be demonstrated. In GOLD I/II failure rates were 17/57 (29.82%) in the Sultamicillin-group and 6/42 (14.29%) in the Placebo-group (risk difference -23.86%&nbsp;[-39.88%; -7.83%]). Safety analysis showed a higher proportion of patients with at least one adverse event in the Sultamicillin group (80/150=53%) compared to Placebo group (60/144=42%, p=0.0453). <b>Conclusion:</b> The trial failed to demonstrate that antibiotic treatment is not needed for patients with acute moderate exacerbations of COPD (AE-COPD) across all stages of the disease. Whereas antibiotic treatment seems unnecessary in GOLD-stages I/II, it cannot be withheld in GOLD-stages III/IV despite its more frequent adverse events.