In the Journals

Azithromycin reduces treatment failure in acute COPD exacerbations

Use of the antibiotic azithromycin on top of standard care may reduce treatment failure in high-risk patients hospitalized for an acute exacerbation of chronic obstructive pulmonary disease, according to new data from the BACE trial.

Researchers in Belgium tested a strategy of adding low-dose azithromycin 500 mg per day on top of standard care prescribed while in hospital and continuing the antibiotic at a dose of 250 mg twice weekly for 3 months after hospitalization, compared with standard care only, including systemic corticosteroids and antibiotics.

Among 301 patients at 20 hospitals in Belgium, the treatment failure rate within 3 months was 49% in the group randomly assigned azithromycin vs. 60% in the group assigned a placebo (HR = 0.73; 95% CI, 0.53-1.01). Treatment failure, the primary endpoint of the BACE trial, was defined as the following: need to intensify treatment with systemic corticosteroids and/or antibiotics; transfer to the ICU or hospital readmission; and death from any cause.

However, the researchers noted that the 18% reduction in the rate of treatment failure within 3 months after hospitalization in the azithromycin group did not meet significance because the BACE trial was underpowered due to early termination after the trial did not meet the enrollment goal of 500 participants.

“Though formally negative, our findings show that a low-dose azithromycin intervention, initiated at the onset of a severe [acute exacerbation] in COPD requiring hospitalization and subsequently administered for 3 months, may strongly reduce the occurrence of exacerbations, especially those leading to hospital admission and transfer to intensive care, in patients at risk. Prolonged treatment, however, seems needed to maintain clinical benefits,” Kristina Vermeersch, MSc, from the department of chronic diseases, metabolism and aging at KU Leuven and the department of respiratory diseases at University Hospitals Leuven, Belgium, and colleagues wrote in the American Journal of Respiratory and Critical Care Medicine.

In other results, the rate of treatment intensification within 3 months was 47% with azithromycin vs. 60% with placebo (P = .0272). Patients in the azithromycin group spent 24% fewer days in the hospital and 74% fewer days in the ICU compared with the placebo group. The rate of all-cause mortality during the study period was lower among those assigned azithromycin: 2% vs. 4% (P = .5023). The rate of mortality related to respiratory causes was 0% in the azithromycin group vs. 2% in the placebo group (P = .2479), and mortality related to cardiovascular causes was 2% vs. 1%, respectively (P = .6783). No significant QTc prolongation was observed among patients assigned azithromycin.

The researchers also observed that the benefits of azithromycin treatment were more pronounced in patients who did not smoke. Those who reported current smoking experienced little to no benefits of treatment with the low-dose azithromycin, according to the findings.

Azithromycin was well-tolerated in this patient population. The frequency of adverse events leading to discontinuation was not significantly different between the two treatment groups.

Upon studying the effects of azithromycin withdrawal after 3 months, the clinical benefits of antibiotic treatment were lost at 6 months, according to the researchers.

Patients in the BACE trial were enrolled and randomly assigned within 48 hours of hospital admission. All patients had diagnosed COPD, at least one exacerbation of COPD that was treated with systemic corticosteroids and/or antibiotics within the past year, current or past smoking history and normal QT interval. The mean age of the patients was 66.5 years and most were men.

The researchers’ goal was to determine whether targeting the highest-risk patients with COPD for a limited period — rather than wide use of azithromycin as a chronic preventive treatment for exacerbations — was beneficial, according to Wim Janssens, MD, PhD, professor of medicine at KU Leuven and pulmonologist at University Hospitals Leuven, Belgium.

“We wanted to establish a new treatment option for acute exacerbations with hospitalization, as current treatments are clearly insufficient,” he said in a press release issued by the American Thoracic Society. “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.”

Although the primary endpoint was not statistically different between the treatment groups, Janssens said the findings of reduced hospital and ICU time is a “positive message of the trial” in this high-risk COPD group. He noted that a large phase 4 study designed with hospital readmission as the primary endpoint would be necessary before broad implementation of the BACE trial’s findings. – by Katie Kalvaitis

Disclosures: The study was funded by the Flemish Government Agency for Innovation by Science and Technology, the Belgium Respiratory Society and TEVA, Belgium. Janssens reports he is supported as a senior clinical researcher by the Fund for Scientific Research Flanders (Belgium) and has received research funding, speaker and consultant fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis. Vermeersch reports she is supported as a doctoral candidate by the Flemish Government Agency for Innovation by Science and Technology (Belgium).

Use of the antibiotic azithromycin on top of standard care may reduce treatment failure in high-risk patients hospitalized for an acute exacerbation of chronic obstructive pulmonary disease, according to new data from the BACE trial.

Researchers in Belgium tested a strategy of adding low-dose azithromycin 500 mg per day on top of standard care prescribed while in hospital and continuing the antibiotic at a dose of 250 mg twice weekly for 3 months after hospitalization, compared with standard care only, including systemic corticosteroids and antibiotics.

Among 301 patients at 20 hospitals in Belgium, the treatment failure rate within 3 months was 49% in the group randomly assigned azithromycin vs. 60% in the group assigned a placebo (HR = 0.73; 95% CI, 0.53-1.01). Treatment failure, the primary endpoint of the BACE trial, was defined as the following: need to intensify treatment with systemic corticosteroids and/or antibiotics; transfer to the ICU or hospital readmission; and death from any cause.

However, the researchers noted that the 18% reduction in the rate of treatment failure within 3 months after hospitalization in the azithromycin group did not meet significance because the BACE trial was underpowered due to early termination after the trial did not meet the enrollment goal of 500 participants.

“Though formally negative, our findings show that a low-dose azithromycin intervention, initiated at the onset of a severe [acute exacerbation] in COPD requiring hospitalization and subsequently administered for 3 months, may strongly reduce the occurrence of exacerbations, especially those leading to hospital admission and transfer to intensive care, in patients at risk. Prolonged treatment, however, seems needed to maintain clinical benefits,” Kristina Vermeersch, MSc, from the department of chronic diseases, metabolism and aging at KU Leuven and the department of respiratory diseases at University Hospitals Leuven, Belgium, and colleagues wrote in the American Journal of Respiratory and Critical Care Medicine.

In other results, the rate of treatment intensification within 3 months was 47% with azithromycin vs. 60% with placebo (P = .0272). Patients in the azithromycin group spent 24% fewer days in the hospital and 74% fewer days in the ICU compared with the placebo group. The rate of all-cause mortality during the study period was lower among those assigned azithromycin: 2% vs. 4% (P = .5023). The rate of mortality related to respiratory causes was 0% in the azithromycin group vs. 2% in the placebo group (P = .2479), and mortality related to cardiovascular causes was 2% vs. 1%, respectively (P = .6783). No significant QTc prolongation was observed among patients assigned azithromycin.

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The researchers also observed that the benefits of azithromycin treatment were more pronounced in patients who did not smoke. Those who reported current smoking experienced little to no benefits of treatment with the low-dose azithromycin, according to the findings.

Azithromycin was well-tolerated in this patient population. The frequency of adverse events leading to discontinuation was not significantly different between the two treatment groups.

Upon studying the effects of azithromycin withdrawal after 3 months, the clinical benefits of antibiotic treatment were lost at 6 months, according to the researchers.

Patients in the BACE trial were enrolled and randomly assigned within 48 hours of hospital admission. All patients had diagnosed COPD, at least one exacerbation of COPD that was treated with systemic corticosteroids and/or antibiotics within the past year, current or past smoking history and normal QT interval. The mean age of the patients was 66.5 years and most were men.

The researchers’ goal was to determine whether targeting the highest-risk patients with COPD for a limited period — rather than wide use of azithromycin as a chronic preventive treatment for exacerbations — was beneficial, according to Wim Janssens, MD, PhD, professor of medicine at KU Leuven and pulmonologist at University Hospitals Leuven, Belgium.

“We wanted to establish a new treatment option for acute exacerbations with hospitalization, as current treatments are clearly insufficient,” he said in a press release issued by the American Thoracic Society. “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.”

Although the primary endpoint was not statistically different between the treatment groups, Janssens said the findings of reduced hospital and ICU time is a “positive message of the trial” in this high-risk COPD group. He noted that a large phase 4 study designed with hospital readmission as the primary endpoint would be necessary before broad implementation of the BACE trial’s findings. – by Katie Kalvaitis

Disclosures: The study was funded by the Flemish Government Agency for Innovation by Science and Technology, the Belgium Respiratory Society and TEVA, Belgium. Janssens reports he is supported as a senior clinical researcher by the Fund for Scientific Research Flanders (Belgium) and has received research funding, speaker and consultant fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis. Vermeersch reports she is supported as a doctoral candidate by the Flemish Government Agency for Innovation by Science and Technology (Belgium).