LEAP2
Trial question
Is oral lefamulin noninferior to moxifloxacin for early clinical response among adults with bacterial community-acquired pneumonia?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
48.0% female
52.0% male
N = 738
738 patients (351 female, 387 male).
Inclusion criteria: adult patients aged ≥ 18 years with a Pneumonia Outcomes Research Team risk class of II, III, or IV; radiographically documented pneumonia; acute illness; ≥ 3 community-acquired bacterial pneumonia symptoms; and ≥ 2 vital sign abnormalities.
Key exclusion criteria: receipt of > 1 dose of a short-acting oral or intravenous antibacterial for CABP within 72 hours before randomization, hospitalization for ≥ 2 days within 90 days, confirmed or suspected methicillin-resistant S aureus, being at risk for major cardiac events or dysfunction, and significant hepatic disease.
Interventions
N=370 lefamulin (600 mg PO every 12 hours for 5 days).
N=368 moxifloxacin (400 mg PO every 24 hours for 7 days).
Primary outcome
Early clinical response rate at 96 hours after first dose
90.8%
90.8%
90.8 %
68.1 %
45.4 %
22.7 %
0.0 %
Lefamulin
Moxifloxacin
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in early clinical response rate at 96 hours after first dose (90.8% vs. 90.8%; ARD 0.1, 97.5% CI -4.4 to Infinity).
Secondary outcomes
No significant difference in overall early clinical response by baseline community-acquired bacterial pneumonia pathogen in microbiological intent-to-treat population (90.7% vs. 93%; ARD -2.3, 95% CI -8.2 to 3.5).
Safety outcomes
No significant differences in serious adverse events, death at 28 days, adverse events leading to discontinuation of study drug or withdrawal from study.
Significant differences in diarrhea (12.2% vs. 1.1%), nausea (5.2% vs. 1.9%), vomiting (3.3% vs. 0.8%).
Conclusion
In adult patients aged ≥ 18 years with a Pneumonia Outcomes Research Team risk class of II, III, or IV; radiographically documented pneumonia; acute illness; ≥ 3 community-acquired bacterial pneumonia symptoms; and ≥ 2 vital sign abnormalities, lefamulin was noninferior to moxifloxacin with respect to early clinical response rate at 96 hours after first dose.
Reference
Elizabeth Alexander, Lisa Goldberg, Anita F Das et al. Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial. JAMA. 2019 Sep 27;322(17):1661-1671.
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