Inhaled liposomal amikacin added to standard therapy raised culture conversion in newly diagnosed MAC lung disease

Design

Phase 3b, randomised, double-blind, placebo-controlled superiority trial (ENCORE)

Population

425 adults with newly diagnosed MAC lung disease, median age 68 years, 79% women

Primary outcome

Change in Respiratory Symptom Score from baseline to month 13

Effect

Treatment difference 3.11 points (P = 0.0299); culture conversion 82.4% vs 55.6%; durable conversion 76.2% vs 47.6%

ENCORE was a double-blind, placebo-controlled phase 3b superiority trial in 425 adults with newly diagnosed Mycobacterium avium complex lung disease who had not started antibiotics. Participants received azithromycin and ethambutol daily for 12 months with either inhaled liposomal amikacin (590 mg daily) or placebo. The median age was 68 years and 79% were women.

The primary endpoint, change in a respiratory symptom score at month 13, favoured the amikacin arm by 3.11 points (17.77 against 14.66; P = 0.0299), with the difference widening to 4.80 points at month 15. Sputum culture conversion by month 13 was 82.4% against 55.6%, and durable conversion at month 15 was 76.2% against 47.6% (both P < 0.0001). No new safety signals were reported in the abstract.

The symptom gain is modest, while the culture conversion gain is large. The drug is approved elsewhere for refractory disease, and use in new disease would be an extension. In India, cost and availability are practical limits, and the trial population (mostly White, mostly women) differs from Indian patients, so the results need caution.

• Confirm the diagnosis with the usual microbiological and radiological criteria and consider whether treatment is needed now
• The comparator in the trial was azithromycin and ethambutol alone; check your regimen against current guidelines
• Culture conversion rose substantially, but the symptom benefit was modest
• Check availability, cost and local regulatory status before planning inhaled amikacin
• Monitor for respiratory adverse effects of inhaled therapy

Why it matters

Standard three-drug therapy for MAC has long had disappointing results, and this tests adding an inhaled agent from the start.

Don't overread it

The trial shows better culture conversion and a modest symptom gain, not a survival or lung function benefit, and it has not changed guidelines.

The statistics, in plain English

Culture conversion of 82.4% against 55.6% means about 27 more patients per 100 cleared their sputum cultures. The symptom difference of 3.11 points is statistically significant but small relative to the scale, so its clinical meaning is less clear. Median ages and demographics differ from Indian practice.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.