Tobramycin inhalation powder for P. aeruginosa infection in cystic fibrosis: the EVOLVE trial.
Tobramycin inhalation solution is used to treat chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients. We evaluated the efficacy and safety of a novel, light-porous particle, dry-powder formulation of tobramycin, which was developed to improve delivery efficiency to the airways and substantially reduce the delivery time. In this randomized, double-blind study, patients with CF (age 6-21 years) received tobramycin inhalation powder (112 mg tobramycin) twice daily (n = 46) or placebo (n = 49) via the T-326 Inhaler for one cycle, followed by two open-label cycles (all patients). Cycles were 28 days on, 28 days off treatment. The primary endpoint was change in forced expiratory volume in 1 sec (FEV1) % predicted from baseline to Day 28 of Cycle 1. The study was terminated early based on positive results in the interim analysis. Tobramycin inhalation powder significantly improved FEV1 % predicted versus placebo at Day 28 (difference 13.3, 95% CI: 5.31-21.28; P = 0.0016). Similar changes in FEV1 were seen in patients switching from placebo to tobramycin inhalation powder in Cycle 2; improvements were maintained over time. Tobramycin inhalation powder also reduced sputum P. aeruginosa density, respiratory-related hospitalization and antipseudomonal antibiotic use versus placebo. The most common adverse event was cough; the frequency of cough was higher in patients receiving placebo (26.5%) versus tobramycin inhalation powder (13.0%) in Cycle 1. Tobramycin inhalation powder was not associated with ototoxicity or nephrotoxicity. Administration time was between 4 and 6 min. In conclusion, tobramycin inhalation powder was effective and well tolerated in CF patients, and may offer an important treatment option to decrease the treatment burden of CF pseudomonas lung infections.
Konstan
Michael W
MW
Rainbow Babies and Children's Hospital, and Case Western Reserve University School of Medicine, Cleveland, Ohio. michael.konstan@uhhospitals.org.
Geller
David E
DE
Minić
Predrag
P
Brockhaus
Florian
F
Zhang
Jie
J
Angyalosi
Gerhild
G
D000280:Administration, Inhalation; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D011208:Powders; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000209:etiology*; D011550:Pseudomonas aeruginosa; D014031:Tobramycin / Q000008:administration & dosage*; D055815:Young Adult
D000900:Anti-Bacterial Agents; D011208:Powders; D014031:Tobramycin