AT CHEST 2016
LOS ANGELES (FRONTLINE MEDICAL NEWS) – Long-term inhaled ciprofloxacin therapy appears to be a safe and effective treatment option in patients with bronchiectasis, results from an international phase III trial showed.
“This is really exciting; it’s the first large study of an inhaled antibiotic to show a benefit in this population,” study investigator Kevin Winthrop, MD, said in an interview prior to the annual meeting of the American College of Chest Physicians. “There’s a tremendous unmet need and a lot of these patients have daily struggles and their quality of life is low. To have something that would improve that would be a benefit for patients and physicians alike.”
In a phase III trial sponsored by Bayer known as RESPIRE 1, Dr. Winthrop and his associates enrolled adult patients with non–cystic fibrosis bronchiectasis who had at least two exacerbations in the prior 12 months and positive bacterial sputum culture for predefined bacteria. Exacerbations were defined as presence of three criteria: systemic antibiotic treatment; worsening of at least three signs and symptoms for at least 48 hours (dyspnea, wheezing, cough, 24-hour sputum volume, or sputum purulence); and fever or malaise/fatigue. A total of 416 patients in Canada, Germany, Spain, the United Kingdom, and the United States were randomized 2:1 to ciprofloxacin 32.5 mg or placebo administered twice per day using a pocket-sized inhaler as a cyclical regimen of either 14 days on/off drug or 28 days on/off drug, for 48 weeks. The primary endpoints were time to first exacerbation and frequency of exacerbation.
Compared with patients in the placebo arm, those in the ciprofloxacin dry powder for inhalation (DPI) 14-day on/off arm experienced a significantly prolonged time to first exacerbation (a mean of 336 days versus 186 days, respectively; adjusted hazard ratio, 0.53; P = .0005) and a significantly reduced exacerbation frequency over 48 weeks (a mean of 0.78 vs. 1.42; adjusted incident rate of 0.61; P = .0061). A nonsignificant trend in favor of ciprofloxacin DPI was observed for both primary endpoints among patients in the 28-day on/off arm (time to first exacerbation: HR, 0.73; P = .065; frequency of exacerbations: adjusted incidence rate ratio, 0.98; P = .89).
Treatment-emergent adverse events and adverse events leading to discontinuation were similar across treatment groups (82% in the ciprofloxacin DPI 14-day on/off arm, 83% in the ciprofloxacin DPI 28-day on/off arm, and 83% in the pooled placebo arm. The rates of serious adverse events were also similar in the three treatment groups (17%, 20%, and 23%, respectively). “Tolerability markers like hoarseness, bronchospasm, shortness of breath, or increased cough didn’t seem to happen with any more frequency in the ciprofloxacin arms,” said Dr. Winthrop, who is an infectious diseases specialist at Oregon Health and Science University, Portland. “The safety profile looks really good. There were no typical fluoroquinolone types of problems such as tendinopathy reported.”
A follow-up trial known as RESPIRE 2 is ongoing. RESPIRE 1 was funded by Bayer. Dr. Winthrop disclosed that he is a consultant for the company.