Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study

Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by complex (MAC). To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients wi...

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Published in:American journal of respiratory and critical care medicine Vol. 198; no. 12; pp. 1559 - 1569
Main Authors: Griffith, David E., Eagle, Gina, Thomson, Rachel, Aksamit, Timothy R., Hasegawa, Naoki, Morimoto, Kozo, Addrizzo-Harris, Doreen J., O’Donnell, Anne E., Marras, Theodore K., Flume, Patrick A., Loebinger, Michael R., Morgan, Lucy, Codecasa, Luigi R., Hill, Adam T., Ruoss, Stephen J., Yim, Jae-Joon, Ringshausen, Felix C., Field, Stephen K., Philley, Julie V., Wallace, Richard J., van Ingen, Jakko, Coulter, Chris, Nezamis, James, Winthrop, Kevin L.
Format: Journal Article
Language:English
Published: United States American Thoracic Society 15.12.2018
Subjects:
Administration, Inhalation
Amikacin - administration & dosage
Amikacin - therapeutic use
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - therapeutic use
Antibiotics
Bacteriology
Chronic obstructive pulmonary disease
Confidence intervals
Female
Humans
Infectious diseases
Life Sciences
Liposomes
Lung diseases
Lung Diseases - drug therapy
Lung Diseases - microbiology
Male
Microbiology and Parasitology
Middle Aged
Mycobacterium avium Complex
Mycobacterium avium-intracellulare Infection - drug therapy
Prospective Studies
Treatment Outcome
Tuberculosis
Australia
Europe
nontuberculous mycobacteria
liposomal amikacin for inhalation
ALIS
culture conversion
guideline-based therapy
ISSN:1073-449X, 1535-4970, 1535-4970
Online Access:Get full text
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Summary:Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by complex (MAC). To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by Month 6. Enrolled patients (ALIS + GBT,  = 224; GBT-alone,  = 112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS + GBT and 10 of 112 (8.9%) with GBT alone (odds ratio, 4.22; 95% confidence interval, 2.08-8.57;  < 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 2.00-7.60). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004).
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ISSN:1073-449X
1535-4970
1535-4970
DOI:10.1164/rccm.201807-1318OC