Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT) a prospective, open-label, randomized study

David E. Griffith, Gina Eagle, Rachel Thomson, Timothy 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 & 4 others Jakko Van Ingen, Chris Coulter, James Nezamis, Kevin L. Winthrop

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 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. 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 (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 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. 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.

Original languageEnglish (US)
Pages (from-to)1559-1569
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume198
Issue number12
DOIs
StatePublished - Dec 15 2018

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Mycobacterium avium Complex
Amikacin
Liposomes
Inhalation
Lung Diseases
Suspensions
Guidelines
Therapeutics
Sputum
Confidence Intervals
Dysphonia

Keywords

  • ALIS
  • Culture conversion
  • Guideline-based therapy
  • Liposomal amikacin for inhalation
  • Nontuberculous mycobacteria

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT) a prospective, open-label, randomized study. / Griffith, David E.; Eagle, Gina; Thomson, Rachel; Aksamit, Timothy; 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.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 198, No. 12, 15.12.2018, p. 1559-1569.

Research output: Contribution to journalArticle

Griffith, DE, Eagle, G, Thomson, R, Aksamit, T, Hasegawa, N, Morimoto, K, Addrizzo-Harris, DJ, O'Donnell, AE, Marras, TK, Flume, PA, Loebinger, MR, Morgan, L, Codecasa, LR, Hill, AT, Ruoss, SJ, Yim, JJ, Ringshausen, FC, Field, SK, Philley, JV, Wallace, RJ, Van Ingen, J, Coulter, C, Nezamis, J & Winthrop, KL 2018, 'Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT) a prospective, open-label, randomized study', American Journal of Respiratory and Critical Care Medicine, vol. 198, no. 12, pp. 1559-1569. https://doi.org/10.1164/rccm.201807-1318OC
Griffith, David E. ; Eagle, Gina ; Thomson, Rachel ; Aksamit, Timothy ; 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. / Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT) a prospective, open-label, randomized study. In: American Journal of Respiratory and Critical Care Medicine. 2018 ; Vol. 198, No. 12. pp. 1559-1569.
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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 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. 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 (odds ratio, 4.22; 95{\%} confidence interval, 2.08-8.57; P < 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. 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.",
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T1 - Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT) a prospective, open-label, randomized study

AU - Griffith, David E.

AU - Eagle, Gina

AU - Thomson, Rachel

AU - Aksamit, Timothy

AU - Hasegawa, Naoki

AU - Morimoto, Kozo

AU - Addrizzo-Harris, Doreen J.

AU - O'Donnell, Anne E.

AU - Marras, Theodore K.

AU - Flume, Patrick A.

AU - Loebinger, Michael R.

AU - Morgan, Lucy

AU - Codecasa, Luigi R.

AU - Hill, Adam T.

AU - Ruoss, Stephen J.

AU - Yim, Jae Joon

AU - Ringshausen, Felix C.

AU - Field, Stephen K.

AU - Philley, Julie V.

AU - Wallace, Richard J.

AU - Van Ingen, Jakko

AU - Coulter, Chris

AU - Nezamis, James

AU - Winthrop, Kevin L.

PY - 2018/12/15

Y1 - 2018/12/15

N2 - 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 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. 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 (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 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. 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.

AB - 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 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. 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 (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 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. 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.

KW - ALIS

KW - Culture conversion

KW - Guideline-based therapy

KW - Liposomal amikacin for inhalation

KW - Nontuberculous mycobacteria

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DO - 10.1164/rccm.201807-1318OC

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