Azithromycin treatment initiated during hospitalization for an acute exacerbation of chronic obstructive pulmonary disease (COPD), followed by three months of a low-maintenance dose, seems to reduce treatment failure.
The results were reported in “Azithromycin during Acute COPD Exacerbations Requiring Hospitalization (BACE): a Multicentre, Randomized, Double-blind, Placebo-controlled Trial,” published in the American Journal of Respiratory and Critical Care Medicine.
According to the team, thirty-five percent of COPD patients who are hospitalized for an acute exacerbation are likely to be readmitted within three months of discharge, during which time they face a 12% increased risk of all-cause mortality.
In the study (NCT02135354), researchers investigated whether adding azithromycin to the standard treatment of hospitalized COPD patients with acute exacerbation (i.e., systemic corticosteroids and other antibiotics), would reduce the high percentage of treatment failure.
Azithromycin is an antibiotic that has previously been proven effective in preventing exacerbations in at-risk, stable patients. However, the team emphasized that this study is the first to evaluate azithromycin’s effects in the setting of a hospitalization for acute exacerbation. The therapy belongs to a family of antibiotics called macrolides, which have been shown to exert broad-ranging immunomodulatory and anti-inflammatory effects in addition to their antibiotic properties.
“We wanted to establish a new treatment option for acute exacerbations with hospitalization as current treatments are clearly insufficient,” Wim Janssens, MD, PhD, senior study author, said in a press release. “Equally important, we wanted to see whether continuing azithromycin for a relatively short time after leaving the hospital could interrupt the vicious cycle of relapse, even after treatment withdrawal.”
The study involved 301 COPD patients at 20 hospitals in Belgium. Patients had a smoking history of 10 or more pack-years (meaning the number of packs of cigarettes smoked per day multiplied by the number of years the person has smoked), and one or more exacerbations in the previous year. Patients received either azithromycin (n=147) or placebo (n=154) during their hospitalization for acute exacerbation, in addition to standard medicines (corticosteroids and antibiotics).
Azithromycin was administered as a 500 mg dose per day for three days, followed by a maintenance dose of 250 mg every two days for three months. Patients were followed for six months thereafter.
The team defined treatment failure (TF) as three possible outcomes: the need to intensify treatment with systemic corticosteroids and/or antibiotics (TI, treatment intensification), to transfer the patients to the intensive care unit or readmit them to the hospital after discharge for respiratory reasons (SH, step-up in hospital care), or death from any cause.
Results showed that within three months of starting treatment, the TF rate was 60% in the placebo group, and 49% in the azithromycin group. The TI, SH, and mortality rates within three months in the placebo versus azithromycin groups were 60% versus 47%, 28% versus 13%, and 4% versus 2%, respectively.
Although the researchers noted that the study did not reach statistical significance for its primary endpoint — time to treatment failure — because they could not recruit the expected number of participants, the data suggested that “three months of azithromycin for acute infectious COPD exacerbation requiring hospitalization may significantly reduce TF during the highest risk period,” they said.
“A positive message of the trial is that our strategy reduced hospital time, days in the [intensive care unit] and recurrent exacerbations in the most severe COPD group,” Janssens said.
However, the team found that the clinical benefits offered by azithromycin were lost six months after stopping the treatment, suggesting that “prolonged treatment seems needed to maintain clinical benefits.”