A 3-month treatment course of low-dose azithromycin for acute exacerbations of chronic obstructive pulmonary disorder (AECOPD) appears to safely reduce treatment failure (TF) by preventing transfer to intensive care or readmission for respiratory causes, according to a posthoc analysis of the BACE* trial presented at the American Thoracic Society (ATS) 2019 International Conference.

The BACE investigators earlier reported that the intervention effectively reduces hospital time, days in the ICU and recurrent exacerbations in patients with most severe COPD group. [Am J Respir Crit Care Med 2019;doi:10.1164/rccm.201901-0094OC]

In the present analysis, they explored the effect of the intervention on subsequent events by breaking up the trial's novel composite endpoint of TF into exclusive components based on severity: mortality and step-up in hospital care (SH; defined as ICU transfer or readmission for respiratory reasons) as severe events and treatment intensification (TI) as a moderate event.

A total of 301 COPD patients with a smoking history of ≥10 pack-years and ≥1 exacerbation in the previous year had been randomized to receive azithromycin (250 mg every 2 days; n=147) or placebo (n=154) within 48-hours of hospital admission. The study drug was administered concomitantly with systemic corticosteroids and antibiotics and subsequently continued for 3 months. Patients were followed for 6 months thereafter.

There were 257 cases of TF documented during the 3-month intervention period (110 in the azithromycin arm vs 147 in the placebo arm; rate ratio [RR], 0.76, 95 percent CI, 0.61–1.00; p=0.05). Of these, 46 TFs (18.3 percent) occurred during the index hospitalization and were mostly moderate events (18 vs 24, respectively; RR, 0.82, 0.43–1.45; p=0.44). [ATS 2019, A1115/P204]

The remaining 210 TFs (81.7 percent) occurred during the postdischarge period, with 131 moderate events (62.4 percent; 65 in the azithromycin arm vs 66 in the placebo arm; RR, 1.03, 0.73–1.45; p=0.86) and 79 severe events (37.6 percent; 26 vs 53, respectively; RR, 0.51, 0.32–0.82; p=0.005).

At month 3, TI did not significantly differ between the two treatment arms (RR, 0.94, 0.72–1.30; p=0.82). On the other hand, azithromycin yielded a significant reduction in SH (RR, 0.48, 0.30–0.80; p=0.004) as well as a nominal decrease in all-cause mortality (RR, 0.52, 0.13–2.09; p=0.36).

All benefits were lost 6 months after treatment withdrawal, suggesting that prolonged treatment may be needed to maintain clinical benefits, according to the investigators.

Overall, the present data indicate that the use of a low-dose azithromycin treatment strategy for 3 months may reduce the recurrence of exacerbation, particularly those leading to hospital admission and transfer to intensive care in patients with severe AECOPD, they added.

The investigators, however, stressed the need for a large phase IV study that uses hospital readmission as the primary endpoint before broad implementation of the treatment strategy.

*Belgian trial with Azithromycin for acute COPD Exacerbations