Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex
CONVERT trial design and results
Design
Prospective, open-label, randomised study
Treatment
Daily amikacin liposome inhalation suspension added to guideline-based therapy
Control
Guideline-based therapy alone
Population
336 patients with treatment-refractory Mycobacterium avium complex lung disease, mean age 64.7 years and 69.3% female; 62.5% had underlying bronchiectasis, 14.3% COPD and 11.9% both
Follow-up
6 months
Primary endpoint
Culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by month 6
Result
Culture conversion was achieved by 65 of 224 (29.0%) with amikacin liposome inhalation suspension plus guideline-based therapy versus 10 of 112 (8.9%) with guideline-based therapy alone — odds ratio 4.22 (95% CI 2.08 to 8.57, p<0.001), hazard ratio 3.90 (2.00 to 7.60). Respiratory adverse events, chiefly dysphonia, cough and dyspnoea, occurred in 87.4% versus 50.0%, while serious treatment-emergent adverse events were comparable at 20.2% and 17.9%.
Secondary endpoints
Durability of conversion, respiratory adverse events, serious adverse events
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.
The trial authors, in the published abstract
How it has aged
The only randomised evidence in a genuinely difficult disease, and the basis for licensing in refractory infection. Two caveats travel with it: the trial is open-label, and culture conversion is a microbiological endpoint rather than a clinical one — 87% of treated patients had respiratory adverse events, which is the trade patients actually experience.
Publications
Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study
Griffith DE, Eagle G, Thomson R, et al. Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study. Am J Respir Crit Care Med 2018 Dec 15;198(12):1559-1569.
Culture conversion by month 6 in 29.0% versus 8.9% with guideline-based therapy alone
Respiratory adverse events in 87.4% versus 50.0%
Comparable rates of serious treatment-emergent adverse events
Open-label design with a microbiological primary endpoint