Amikacin Liposome Inhalation Suspension for Refractory Mycobacterium avium Complex Lung Disease: Sustainability and Durability of Culture Conversion and Safety of Long-term Exposure

Chest. 2021 Sep;160(3):831-842. doi: 10.1016/j.chest.2021.03.070. Epub 2021 Apr 19.

Abstract

Background: In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex lung disease (ALIS plus GBT, 29% [65/224] vs GBT alone, 8.9% [10/112]; P < .0001).

Research question: In patients who achieved culture conversion by month 6 in the CONVERT study, was conversion sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for 3 months after treatment) and were there any additional safety signals associated with a full treatment course of 12 months after conversion?

Study design and methods: Adults were randomized 2:1 to receive ALIS plus GBT or GBT alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation.

Results: More patients randomized to ALIS plus GBT (intention-to-treat population) achieved conversion that was both sustained and durable 3 months after treatment vs patients randomized to GBT alone (ALIS plus GBT, 16.1% [36/224] vs GBT alone, 0% [0/112]; P < .0001). Of the patients who achieved culture conversion by month 6, 55.4% of converters (36/65) in the ALIS plus GBT treated arm vs no converters (0/10) in the GBT alone arm achieved sustained and durable conversion (P = .0017). Relapse rates through 3 months after treatment were 9.2% (6/65) in the ALIS plus GBT arm and 30.0% (3/10) in the GBT alone arm. Common adverse events among ALIS plus GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) occurred mainly within the first 8 months of treatment.

Interpretation: In a refractory population, conversion was sustained and durable in more patients treated with ALIS plus GBT for 12 months after conversion than in those treated with GBT alone. No new safety signals were associated with 12 months of treatment after conversion.

Trial registry: ClinicalTrials.gov; No.: NCT02344004; URL: www.clinicaltrials.gov.

Keywords: ALIS; Mycobacterium avium complex; culture conversion; durability; nontuberculous mycobacteria.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Amikacin* / administration & dosage
  • Amikacin* / adverse effects
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Bacteriological Techniques / methods
  • Drug Monitoring / methods*
  • Female
  • Humans
  • Liposomes
  • Long Term Adverse Effects* / classification
  • Long Term Adverse Effects* / diagnosis
  • Lung Diseases* / diagnosis
  • Lung Diseases* / drug therapy
  • Lung Diseases* / microbiology
  • Male
  • Mycobacterium avium Complex / isolation & purification*
  • Mycobacterium avium-intracellulare Infection* / diagnosis
  • Mycobacterium avium-intracellulare Infection* / drug therapy
  • Mycobacterium avium-intracellulare Infection* / physiopathology
  • Sputum / microbiology
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Liposomes
  • Amikacin

Associated data

  • ClinicalTrials.gov/NCT02344004