Amikacin Liposome Inhalation Suspension in Newly Diagnosed Mycobacterium avium Complex Lung Disease: A Phase 3b, Double-blind, Randomized Clinical Trial (ENCORE)
In brief
Inhaled amikacin raised culture conversion from 56% to 82% in MAC lung disease
In 425 adults newly diagnosed with Mycobacterium avium complex lung disease, adding inhaled amikacin to multidrug therapy raised culture conversion at month 13 from 55.6% to 82.4%; more patients also maintained conversion at month 15. Respiratory symptoms improved more with amikacin, though the difference was modest, and the 12-month trial found no new safety signals.
- Journal
- American journal of respiratory and critical care medicine (Q1)
- Published
- 30 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Charles L Daley, Kozo Morimoto, Rachel Thomson, Eva Van Braeckel, Naoki Hasegawa, David E Griffith, et al.
- PMID
- 42814876
- DOI
- 10.1093/ajrccm/aamag530
Why clinicians should know about it
- Picked for Microbiology (medical) (top studies of the week, 4 October 2026): High-quality evidence in a top journal
- Picked for Pulmonary and Respiratory Medicine (top studies of the week, 4 October 2026): ALIS superior for respiratory symptom improvement and culture conversion
Abstract
RATIONALE: Current recommended front-line multidrug therapy (MDT) for Mycobacterium avium complex lung disease (MACLD) produces suboptimal outcomes. Amikacin liposome inhalation suspension (ALIS) with MDT is approved for refractory MACLD; however, clinical trial evidence in newly diagnosed MACLD is lacking. OBJECTIVES: To evaluate efficacy and safety of ALIS with MDT in the phase 3b, randomized, double-blind, placebo-controlled superiority trial in adults newly diagnosed with MACLD who have not initiated antibiotics (ENCORE NCT04677569). METHODS: Patients (N = 425) were randomized 1:1 to receive ALIS 590 mg (n = 213) or placebo (n = 212) plus azithromycin 250 mg and ethambutol 15 mg/kg once daily for 12 months. Primary endpoint was change from baseline to month 13 in Respiratory Symptom Score (RSS). Pre-specified secondary endpoints included culture conversion (CC) at clinically important timepoints, durable culture conversion (DCC), and safety. RESULTS: Median age was 68.0 years, 62.8% were White, and 79.3% were female. Significantly greater improvements in RSS were observed in the ALIS versus comparator arm at 1 month post-treatment (month 13; LS mean change: 17.77 vs 14.66 points; treatment difference 3.11 points; P=0.0299), with improvements sustained at 3 months post-treatment (month 15; treatment arm difference 4.80 points; nominal P=0.0015). Significantly greater proportions of patients achieved CC by month 13 and DCC at month 15 in the ALIS arm versus comparator arm (82.4% vs 55.6% and 76.2% vs 47.6%, respectively; both P<0.0001). No new safety signals were observed. CONCLUSIONS: ALIS with MDT was superior to the comparator arm for improving respiratory symptoms and CC in patients newly diagnosed with MACLD.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.