title: Randomized Trial of Liposomal Amikacin for Inhalation in Nontuberculous Mycobacterial Lung Disease.
abstract: Lengthy, multidrug, toxic, and low-efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease.
  
  
  
  In this phase II study, we investigated the efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease.
  
  
  
  During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute-walk distance, and adverse events.
  
  
  
  The modified intention-to-treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. The primary endpoint was not achieved (P = 0.072); however, a greater proportion of the LAI group demonstrated at least one negative sputum culture (14 [32%] of 44 vs. 4 [9%] of 45; P = 0.006) and improvement in 6-minute-walk test (+20.6 m vs. -25.0 m; P = 0.017) at Day 84. A treatment effect was seen predominantly in patients without cystic fibrosis with MAC and was sustained 1 year after LAI. Most adverse events were respiratory, and in some patients it led to drug discontinuation.
  
  
  
  Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6-minute-walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research in this area is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01315236).
authors.affiliation: 1 National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kenneth N
authors.identifier: 0000-0001-8200-255X
authors.initials: KN
authors.lastname: Olivier
authors.affiliation: 2 The University of Texas Health Science Center at Tyler, Tyler, Texas.
authors.forename: David E
authors.initials: DE
authors.lastname: Griffith
authors.affiliation: 3 Insmed Incorporated, Bridgewater, New Jersey.
authors.forename: Gina
authors.initials: G
authors.lastname: Eagle
authors.affiliation: 3 Insmed Incorporated, Bridgewater, New Jersey.
authors.forename: John P
authors.initials: JP
authors.lastname: McGinnis
authors.affiliation: 3 Insmed Incorporated, Bridgewater, New Jersey.
authors.forename: Liza
authors.initials: L
authors.lastname: Micioni
authors.affiliation: 3 Insmed Incorporated, Bridgewater, New Jersey.
authors.forename: Keith
authors.initials: K
authors.lastname: Liu
authors.affiliation: 4 National Jewish Health, Denver, Colorado.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Daley
authors.affiliation: 5 Oregon Health & Science University, Portland, Oregon.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Winthrop
authors.affiliation: 6 Stanford University School of Medicine, Stanford, California.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ruoss
authors.affiliation: 7 New York University School of Medicine, New York, New York.
authors.forename: Doreen J
authors.initials: DJ
authors.lastname: Addrizzo-Harris
authors.affiliation: 8 Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Flume
authors.affiliation: 9 Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dorgan
authors.affiliation: 10 Leonard M. Miller School of Medicine, University of Miami, Miami, Florida; and.
authors.forename: Matthias
authors.initials: M
authors.lastname: Salathe
authors.affiliation: 2 The University of Texas Health Science Center at Tyler, Tyler, Texas.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Brown-Elliott
authors.affiliation: 3 Insmed Incorporated, Bridgewater, New Jersey.|11 Global Biopharma, Moorestown, New Jersey.
authors.forename: Renu
authors.initials: R
authors.lastname: Gupta
authors.affiliation: 2 The University of Texas Health Science Center at Tyler, Tyler, Texas.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wallace
mesh_terms: D000280:Administration, Inhalation; D000583:Amikacin / Q000008:administration & dosage / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy*; D009170:Nontuberculous Mycobacteria / Q000187:drug effects*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000583:Amikacin
keywords: culture conversion; efficacy; nontuberculous mycobacteria; safety