For patients with bronchiectasis of non-cystic fibrosis, an inhaled powder form under investigation of ciprofloxacin may significantly reduce the frequency of exacerbations, phase 3 results of the RESPIRE 1 test.
“This is the first double-blind randomized inhaled antibiotic trial to suggest efficacy in bronchiectasis of non-cystic fibrosis,” said lead researcher Kevin Winthrop, MD, of the University of Oregon Health & Science in Portland. “I’m very encouraged.”
“There is a tremendous unmet need for this orphan disease because there are no approved therapies for its treatment,” he said here at Post 2016: American College of Chest Physicians Annual Meeting.
“Many of these patients develop resistant bacteria over time that make outpatient treatment of exacerbations difficult,” said Neil Freedman, MD, of the NorthShore University Health System in Evanston, Ill., Who is chair of the program’s scientific committee CHEST.
“At present, there are only a few inhaled antibiotics, and availability is limited by the cost. An additional inhaled antibiotic would be very useful for physicians who treat this patient population,” he said.
Dr. Winthrop and his colleagues randomly assigned 416 adults to one of three groups for 48 weeks: twice-daily inhaled ciprofloxacin administered in 12 14-day, 14-day rest periods; ciprofloxacin twice daily given in six 28 day cycles, 28 days rest; and placebo.
All study participants had been treated for at least two exacerbations in the previous 12 months and all had a positive culture for one of seven organisms: Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Stenotrophomonas maltophilia and Burkholderia cepacia .
The criteria for assessing the exacerbation were a combination of three criteria: fever; need for systemic antibiotics; and the worsening of three signs and symptoms, such as dyspnoea, cough and wheezing.
During the 48-week study period, the number of exacerbations was significantly lower with the 14-day regimen than with placebo (adjusted risk ratio [HR], 0.53; P = .0005). The number was also lower with the 28-day regimen than with the placebo, but the difference was not significant (HR, 0.73, P = 0.0650).
Exacerbations were 39% less frequent with the 14-day regimen than with placebo (P = 0.0061), but the difference in frequency between the 28-day regimen and placebo was not significant.
“In terms of safety and tolerability, we are very happy,” Dr. Winthrop reported. “Sometimes these therapies may be difficult to tolerate, but that does not seem to be the case in BREATHE 1.”
Serious adverse event rates in serious treatment were similar with the 14-day regimen, 28-day regimen, and placebo (16.9% vs 19.9% vs 23.4%). The discontinuation rates related to these events were low and evenly distributed among the three groups.
Data on respiratory adverse events – including bronchospasm and hemoptysis – were also encouraging, he said. Interruption rates due to respiratory adverse events were similar: 6% for clustered ciprofloxacin groups and about 8% for placebo.
“There were no cases of tendonitis or tendon rupture that we thought were related to treatment,” Dr. Winthrop said.
“This is a specially formulated version of ciprofloxacin,” he explained. “About 40%, once inhaled, reaches the alveolar space and there is very little systemic absorption. I would not expect to see this, and we have not seen it to date.”
A “very necessary” treatment option
“BREATHE 1, a large randomized controlled trial, demonstrates the clinical efficacy and tolerability of inhaled ciprofloxacin,” said Charlotte Suppli Ulrik, MD, of Hvidovre Hospital and University of Copenhagen, Denmark.
“Management of frequent exacerbations in bronchiectasis does not [cystic fibrosis] is a challenge, with very limited evidence of the various treatment options,” said Dr. Ulrik, who was involved in a recent systematic review of antibiotic therapy for non-cystic fibrosis stable Bronchiectasis (Chron Respir Dis Posted online August 9, 2016).
Studies that add to these very promising findings could lead to “the implementation of a much-needed treatment option in clinical practice for this relatively large group of patients,” Medscape Medical News said.
Several previous trials have not shown benefit for patients with bronchiectasis of non-cystic fibrosis, “so this is exciting,” Dr. Winthrop told Medscape Medical News. The results of phase 3 of the RESPIRE 2 trial are expected soon, he reported.
The study was sponsored by Bayer. Dr Winthrop reports receiving consulting fees from Bayer and Raptor. Dr. Ulrik has disclosed no relevant financial relationship.