Patrick A Flume1, John P Clancy2, George Z Retsch-Bogart3, D Elizabeth Tullis4, Mark Bresnik5, P Alex Derchak6, Sandra A Lewis7, Bonnie W Ramsey8. 1. Medical University of South Carolina, 96 Jonathan Lucas Street, 812-CSB, Charleston, SC 29425, USA. Electronic address: flumepa@musc.edu. 2. Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA. Electronic address: John.clancy@cchmc.org. 3. University of North Carolina at Chapel Hill, Division of Pediatric Pulmonology, 450 MacNider Hall, CB#7217, 333 S. Columbia St., Chapel Hill, NC 27599-7217, USA. Electronic address: gzrb@med.unc.edu. 4. University of Toronto, Division of Respirology, St Michael's Hospital 6-049, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada. Electronic address: TULLISE@smh.ca. 5. Gilead Sciences, 333 Lakeside Dr., Foster City, CA 94404, USA. Electronic address: mark.bresnik@gilead.com. 6. Gilead Sciences, 333 Lakeside Dr., Foster City, CA 94404, USA. Electronic address: alex.derchak@gilead.com. 7. Gilead Sciences, 199 E. Blaine St., Seattle, WA 98102, USA. Electronic address: sandy.lewis@gilead.com. 8. University of Washington, Seattle Children's Hospital, 4800 Sand Point Way NE, Seattle, WA 98105, USA. Electronic address: bonnie.ramsey@seattlechildrens.org.
Abstract
BACKGROUND:Inhaled antibiotics are standard of care for treating chronic pseudomonal respiratory infections in cystic fibrosis patients, initially approved for intermittent administration. However, use of continuous inhaled antibiotic regimens of differing combinations is growing. METHODS: This double-blind trial compared continuous alternating therapy (CAT) to an intermittent treatment regimen. Subjects were treated with 3cycles of 28-days inhaled aztreonam (AZLI) or placebo 3-times daily alternating with 28-days open-label tobramycin inhalation solution (TIS). RESULTS:90 subjects were randomized over 18months. Study enrollment was limited, in part because of evolving practices by clinicians of adopting a CAT regimen in clinical practice; consequently the study was underpowered. AZLI/TIS treatment reduced exacerbation rates by 25.7% (p=0.25; primary endpoint) and rates of respiratory hospitalizations by 35.8% compared with placebo/TIS (p=0.14). AZLI/TIS CAT therapy was well tolerated. CONCLUSIONS: This trial illustrates challenges with studying treatment regimens in a constantly evolving CF care environment. Nonetheless, the results of this trial indicate that AZLI/TIS CAT is well tolerated and may provide additional clinical benefit in CF patients compared with intermittent use of TIS alone. Clinicaltrials.gov: NCT01641822. Copyright Â
RCT Entities:
BACKGROUND: Inhaled antibiotics are standard of care for treating chronic pseudomonal respiratory infections in cystic fibrosispatients, initially approved for intermittent administration. However, use of continuous inhaled antibiotic regimens of differing combinations is growing. METHODS: This double-blind trial compared continuous alternating therapy (CAT) to an intermittent treatment regimen. Subjects were treated with 3cycles of 28-days inhaled aztreonam (AZLI) or placebo 3-times daily alternating with 28-days open-label tobramycin inhalation solution (TIS). RESULTS: 90 subjects were randomized over 18months. Study enrollment was limited, in part because of evolving practices by clinicians of adopting a CAT regimen in clinical practice; consequently the study was underpowered. AZLI/TIS treatment reduced exacerbation rates by 25.7% (p=0.25; primary endpoint) and rates of respiratory hospitalizations by 35.8% compared with placebo/TIS (p=0.14). AZLI/TIS CAT therapy was well tolerated. CONCLUSIONS: This trial illustrates challenges with studying treatment regimens in a constantly evolving CF care environment. Nonetheless, the results of this trial indicate that AZLI/TIS CAT is well tolerated and may provide additional clinical benefit in CFpatients compared with intermittent use of TIS alone. Clinicaltrials.gov: NCT01641822. Copyright Â
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