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LONDON – In patients with non–cystic fibrosis bronchiectasis (NCFB), use of inhaled ciprofloxacin on a schedule of 14 days on and 14 days off significantly reduced the rate of exacerbations, in a multicenter placebo-controlled trial. The results were presented at the annual congress of the European Respiratory Society.
“At last, an antibiotic intervention trial [in NCFB] with a positive outcome,” reported Anthony De Soyza, MBChB, PhD, senior lecturer in respiratory medicine, Newcastle (England) University. Dr. De Soyza was the study’s principal investigator.
In this study, called RESPIRE 1, the researchers conducted two placebo-controlled arms simultaneously. In one, patients randomized to inhaled ciprofloxacin or placebo took their assigned treatment twice daily for 14 days on and then 14 days off. In the other, patients took their assigned treatment of ciprofloxacin or placebo twice daily, but for 28 days on and then 28 days off. The on-off schedules were maintained for 48 weeks. The ratio of randomization of active therapy to placebo was 2:1.
There were two co-primary endpoints. One was the number of exacerbations over the 48 weeks of follow-up. Exacerbations were strictly defined as the worsening of at least three respiratory symptoms (dyspnea, wheezing, cough, increased sputum volume over 24 hours, or increased sputum purulence) plus fever with malaise or fatigue, and systemic antibiotic use. The other endpoint was the time to first exacerbation.
When the 111 patients randomized to the 14-day on-off regimen of inhaled ciprofloxacin were compared to 49 placebo patients, the mean number of exacerbations over 48 weeks of follow-up was 0.6 in the active treatment group, versus 1.0 in the placebo group (adjusted hazard ratio of 0.61, P = .0061), according to Dr. De Soyza.
The mean time to first exacerbation approached 1 year in those randomized to the 14-day on-off schedule of inhaled ciprofloxacin. In the two placebo arms (pooled for this analysis), the mean time to first exacerbation was 186 days. This difference was highly significant (HR = 0.53; P = .0005).
On the 28-day schedule, for 174 patients, there was a trend for a delay in the time to first exacerbation (HR 0.73; P = .0650) for those randomized to inhaled ciprofloxacin relative to placebo. The difference in the mean number of exacerbations between patients in the experimental group and the placebo group did not approach significance, which Dr. De Soyza said may have been caused by a lack of protection from antibiotics during the off period.
Ciprofloxacin, which was delivered in a dose of 32.5 mg in a proprietary dry powder inhalation device, was well tolerated. The overall rate of adverse events was similar across the study arms. The rates of discontinuation for adverse events in the 14-day and 28-day arms of ciprofloxacin were 12.5% and 10.6%, respectively. These rates were numerically lower than the 13.9% rate of adverse events that occurred among the patients receiving placebos.
According to previously published data cited by Dr. De Soyza, the proportion of NCFB patients with chronic lung infections is 70%, and approximately 40% of these patients have at least two exacerbations per year. In patients with at least two exacerbations per year, the 4-year mortality rate is 15%, Dr. De Soyza reported.
“There is an urgent medical need for better therapeutic strategies to improve outcome in patients with this disease,” he emphasized.
In this particular study, enrolled patients had relatively advanced NCFB. About 30% had a baseline forced expiratory volume in one second of less than 50% of predicted, about 55% had experienced two or more exacerbations in the past 12 months, 20% had been hospitalized in the last year, and more than 15% were on long-term oral macrolides, Dr. De Soyza reported.
These data will be rendered even more compelling if the similarly designed and nearly completed RESPIRE 2 trial produces similar results, he said. If both studies demonstrate protection from exacerbations, they might lead to “a paradigm shift” in the treatment of NCFB, he added.
In the context of the limited strategies currently available for NCFB, “the punch line is that this is a really exciting outcome,” he said.
Dr. De Soyza has financial relationships with AstraZeneca, Bayer, Chiesi, Forrest Labs, GlaxoSmithKline, Novartis, and Teva.
LONDON – In patients with non–cystic fibrosis bronchiectasis (NCFB), use of inhaled ciprofloxacin on a schedule of 14 days on and 14 days off significantly reduced the rate of exacerbations, in a multicenter placebo-controlled trial. The results were presented at the annual congress of the European Respiratory Society.
“At last, an antibiotic intervention trial [in NCFB] with a positive outcome,” reported Anthony De Soyza, MBChB, PhD, senior lecturer in respiratory medicine, Newcastle (England) University. Dr. De Soyza was the study’s principal investigator.
In this study, called RESPIRE 1, the researchers conducted two placebo-controlled arms simultaneously. In one, patients randomized to inhaled ciprofloxacin or placebo took their assigned treatment twice daily for 14 days on and then 14 days off. In the other, patients took their assigned treatment of ciprofloxacin or placebo twice daily, but for 28 days on and then 28 days off. The on-off schedules were maintained for 48 weeks. The ratio of randomization of active therapy to placebo was 2:1.
There were two co-primary endpoints. One was the number of exacerbations over the 48 weeks of follow-up. Exacerbations were strictly defined as the worsening of at least three respiratory symptoms (dyspnea, wheezing, cough, increased sputum volume over 24 hours, or increased sputum purulence) plus fever with malaise or fatigue, and systemic antibiotic use. The other endpoint was the time to first exacerbation.
When the 111 patients randomized to the 14-day on-off regimen of inhaled ciprofloxacin were compared to 49 placebo patients, the mean number of exacerbations over 48 weeks of follow-up was 0.6 in the active treatment group, versus 1.0 in the placebo group (adjusted hazard ratio of 0.61, P = .0061), according to Dr. De Soyza.
The mean time to first exacerbation approached 1 year in those randomized to the 14-day on-off schedule of inhaled ciprofloxacin. In the two placebo arms (pooled for this analysis), the mean time to first exacerbation was 186 days. This difference was highly significant (HR = 0.53; P = .0005).
On the 28-day schedule, for 174 patients, there was a trend for a delay in the time to first exacerbation (HR 0.73; P = .0650) for those randomized to inhaled ciprofloxacin relative to placebo. The difference in the mean number of exacerbations between patients in the experimental group and the placebo group did not approach significance, which Dr. De Soyza said may have been caused by a lack of protection from antibiotics during the off period.
Ciprofloxacin, which was delivered in a dose of 32.5 mg in a proprietary dry powder inhalation device, was well tolerated. The overall rate of adverse events was similar across the study arms. The rates of discontinuation for adverse events in the 14-day and 28-day arms of ciprofloxacin were 12.5% and 10.6%, respectively. These rates were numerically lower than the 13.9% rate of adverse events that occurred among the patients receiving placebos.
According to previously published data cited by Dr. De Soyza, the proportion of NCFB patients with chronic lung infections is 70%, and approximately 40% of these patients have at least two exacerbations per year. In patients with at least two exacerbations per year, the 4-year mortality rate is 15%, Dr. De Soyza reported.
“There is an urgent medical need for better therapeutic strategies to improve outcome in patients with this disease,” he emphasized.
In this particular study, enrolled patients had relatively advanced NCFB. About 30% had a baseline forced expiratory volume in one second of less than 50% of predicted, about 55% had experienced two or more exacerbations in the past 12 months, 20% had been hospitalized in the last year, and more than 15% were on long-term oral macrolides, Dr. De Soyza reported.
These data will be rendered even more compelling if the similarly designed and nearly completed RESPIRE 2 trial produces similar results, he said. If both studies demonstrate protection from exacerbations, they might lead to “a paradigm shift” in the treatment of NCFB, he added.
In the context of the limited strategies currently available for NCFB, “the punch line is that this is a really exciting outcome,” he said.
Dr. De Soyza has financial relationships with AstraZeneca, Bayer, Chiesi, Forrest Labs, GlaxoSmithKline, Novartis, and Teva.
LONDON – In patients with non–cystic fibrosis bronchiectasis (NCFB), use of inhaled ciprofloxacin on a schedule of 14 days on and 14 days off significantly reduced the rate of exacerbations, in a multicenter placebo-controlled trial. The results were presented at the annual congress of the European Respiratory Society.
“At last, an antibiotic intervention trial [in NCFB] with a positive outcome,” reported Anthony De Soyza, MBChB, PhD, senior lecturer in respiratory medicine, Newcastle (England) University. Dr. De Soyza was the study’s principal investigator.
In this study, called RESPIRE 1, the researchers conducted two placebo-controlled arms simultaneously. In one, patients randomized to inhaled ciprofloxacin or placebo took their assigned treatment twice daily for 14 days on and then 14 days off. In the other, patients took their assigned treatment of ciprofloxacin or placebo twice daily, but for 28 days on and then 28 days off. The on-off schedules were maintained for 48 weeks. The ratio of randomization of active therapy to placebo was 2:1.
There were two co-primary endpoints. One was the number of exacerbations over the 48 weeks of follow-up. Exacerbations were strictly defined as the worsening of at least three respiratory symptoms (dyspnea, wheezing, cough, increased sputum volume over 24 hours, or increased sputum purulence) plus fever with malaise or fatigue, and systemic antibiotic use. The other endpoint was the time to first exacerbation.
When the 111 patients randomized to the 14-day on-off regimen of inhaled ciprofloxacin were compared to 49 placebo patients, the mean number of exacerbations over 48 weeks of follow-up was 0.6 in the active treatment group, versus 1.0 in the placebo group (adjusted hazard ratio of 0.61, P = .0061), according to Dr. De Soyza.
The mean time to first exacerbation approached 1 year in those randomized to the 14-day on-off schedule of inhaled ciprofloxacin. In the two placebo arms (pooled for this analysis), the mean time to first exacerbation was 186 days. This difference was highly significant (HR = 0.53; P = .0005).
On the 28-day schedule, for 174 patients, there was a trend for a delay in the time to first exacerbation (HR 0.73; P = .0650) for those randomized to inhaled ciprofloxacin relative to placebo. The difference in the mean number of exacerbations between patients in the experimental group and the placebo group did not approach significance, which Dr. De Soyza said may have been caused by a lack of protection from antibiotics during the off period.
Ciprofloxacin, which was delivered in a dose of 32.5 mg in a proprietary dry powder inhalation device, was well tolerated. The overall rate of adverse events was similar across the study arms. The rates of discontinuation for adverse events in the 14-day and 28-day arms of ciprofloxacin were 12.5% and 10.6%, respectively. These rates were numerically lower than the 13.9% rate of adverse events that occurred among the patients receiving placebos.
According to previously published data cited by Dr. De Soyza, the proportion of NCFB patients with chronic lung infections is 70%, and approximately 40% of these patients have at least two exacerbations per year. In patients with at least two exacerbations per year, the 4-year mortality rate is 15%, Dr. De Soyza reported.
“There is an urgent medical need for better therapeutic strategies to improve outcome in patients with this disease,” he emphasized.
In this particular study, enrolled patients had relatively advanced NCFB. About 30% had a baseline forced expiratory volume in one second of less than 50% of predicted, about 55% had experienced two or more exacerbations in the past 12 months, 20% had been hospitalized in the last year, and more than 15% were on long-term oral macrolides, Dr. De Soyza reported.
These data will be rendered even more compelling if the similarly designed and nearly completed RESPIRE 2 trial produces similar results, he said. If both studies demonstrate protection from exacerbations, they might lead to “a paradigm shift” in the treatment of NCFB, he added.
In the context of the limited strategies currently available for NCFB, “the punch line is that this is a really exciting outcome,” he said.
Dr. De Soyza has financial relationships with AstraZeneca, Bayer, Chiesi, Forrest Labs, GlaxoSmithKline, Novartis, and Teva.
AT THE ERS CONGRESS 2016
Key clinical point: An every-14-day regimen of inhaled ciprofloxacin reduced the number of and the rate of exacerbations in non–cystic fibrosis bronchiectasis patients.
Major finding: The rate of exacerbations was reduced by 39% over a 48-week period in those randomized to the inhaled antibiotic relative to placebo.
Data source: A multicenter double-blind, placebo-controlled trial.
Disclosures: Dr. De Soyza has financial relationships with AstraZeneca, Bayer, Chiesi, Forrest Labs, GlaxoSmithKline, Novartis, and Teva.