Title |
Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study
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Published in |
American Journal of Respiratory & Critical Care Medicine, September 2018
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DOI | 10.1164/rccm.201807-1318oc |
Pubmed ID | |
Authors |
David E Griffith, Gina Eagle, Rachel Thomson, Timothy R Aksamit, Naoki Hasegawa, Kozo Morimoto, Doreen J Addrizzo-Harris, Anne E O'Donnell, Theodore K Marras, Patrick A Flume, Michael R Loebinger, Lucy Morgan, Luigi R Codecasa, Adam T Hill, Stephen J Ruoss, Jae-Joon Yim, Felix C Ringshausen, Stephen K Field, Julie V Philley, Richard J Wallace, Jakko van Ingen, Chris Coulter, James Nezamis, Kevin L Winthrop |
Abstract |
Rationale Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives 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. Methods Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite ≥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 3 consecutive monthly MAC-negative sputum cultures by month 6. Measurements and Main Results Enrolled patients (ALIS+GBT, n=224; GBT-alone, n=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 (OR, 4.22; 95% CI [2.08, 8.57]; P<0.001). Patients in the ALIS+GBT arm vs GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% CI, [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. Conclusions 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 registration available at www.clinicaltrials.gov, ID NCT02344004. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 5 | 24% |
United Kingdom | 2 | 10% |
Japan | 2 | 10% |
Germany | 1 | 5% |
France | 1 | 5% |
Sweden | 1 | 5% |
Unknown | 9 | 43% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 15 | 71% |
Practitioners (doctors, other healthcare professionals) | 3 | 14% |
Scientists | 2 | 10% |
Science communicators (journalists, bloggers, editors) | 1 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 213 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 36 | 17% |
Student > Ph. D. Student | 20 | 9% |
Student > Master | 19 | 9% |
Student > Bachelor | 15 | 7% |
Other | 13 | 6% |
Other | 34 | 16% |
Unknown | 76 | 36% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 59 | 28% |
Pharmacology, Toxicology and Pharmaceutical Science | 20 | 9% |
Biochemistry, Genetics and Molecular Biology | 11 | 5% |
Immunology and Microbiology | 6 | 3% |
Agricultural and Biological Sciences | 5 | 2% |
Other | 32 | 15% |
Unknown | 80 | 38% |