RESPIRE 2: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis

Eur Respir J. 2018 Jan 25;51(1):1702053. doi: 10.1183/13993003.02053-2017. Print 2018 Jan.

Abstract

We evaluated the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis, two or more exacerbations in the previous year and predefined sputum bacteria.Patients were randomised 2:1 to twice-daily ciprofloxacin DPI 32.5 mg or placebo in 14- or 28-day on/off treatment cycles for 48 weeks. Primary end-points were time to first exacerbation and frequency of exacerbations. Enrolling countries and α level split (0.049 and 0.001 for 14- and 28-day cycles, respectively) differed from RESPIRE 1.Patients were randomised to ciprofloxacin DPI (14 days on/off (n=176) or 28 days on/off (n=171)) or placebo (14 days on/off (n=88) or 28 days on/off (n=86)). The exacerbation rate was low across treatment arms (mean±sd 0.6±0.9). Active treatment showed trends to prolonged time to first exacerbation (ciprofloxacin DPI 14 days on/off: hazard ratio 0.87, 95.1% CI 0.62-1.21; p=0.3965; ciprofloxacin DPI 28 days on/off: hazard ratio 0.71, 99.9% CI 0.39-1.27; p=0.0511) and reduced frequency of exacerbations (ciprofloxacin DPI 14 days on/off: incidence rate ratio 0.83, 95.1% CI 0.59-1.17; p=0.2862; ciprofloxacin DPI 28 days on/off: incidence rate ratio 0.55, 99.9% CI 0.30-1.02; p=0.0014), although neither achieved statistical significance. Ciprofloxacin DPI was well tolerated.Trends towards clinical benefit were seen with ciprofloxacin DPI, but primary end-points were not met.

Trial registration: ClinicalTrials.gov NCT02106832.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Bronchiectasis / drug therapy*
  • Ciprofloxacin / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule*
  • Dry Powder Inhalers*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Powders*
  • Proportional Hazards Models
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / drug effects
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Powders
  • Ciprofloxacin

Associated data

  • ClinicalTrials.gov/NCT02106832