Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial.

Title

Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial.

Creator

File TM; Goldberg L; Das A; Sweeney C; Saviski J; Gelone SP; Seltzer E; Paukner S; Wicha WW; Talbot GH; Gasink LB

Publisher

Clinical Infectious Diseases

Date

2019
2019-11-13

Description

BACKGROUND: Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP. METHODS: In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours. After 6 doses, patients could be switched to an oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, either linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US Food and Drug Administration primary endpoint was an early clinical response (ECR) 96 ± 24 hours after the first dose of the study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The European Medicines Agency co-primary endpoints were an investigator assessment of clinical response (IACR) 5-10 days after the last dose of the study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%). RESULTS: There were 551 patients randomized (n = 276 lefamulin; n = 275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%, respectively; difference -2.9%, 95% confidence interval [CI] g -8.5 to 2.8) and IACR (mITT, 81.7% vs 84.2%, respectively; difference -2.6%, 95% CI -8.9 to 3.9; CE, 86.9% vs 89.4%, respectively; difference -2.5%, 95% CI -8.4 to 3.4). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin. CONCLUSIONS: Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated. CLINICAL TRIALS REGISTRATION: NCT02559310.

Subject

Aged; Humans; Male; Adult; Female; Middle Aged; Double-Blind Method; Administration Intravenous; Microbial Sensitivity Tests; pneumonia; Randomized Controlled Trials as Topic; antibiotic; lefamulin; moxifloxacin; pleuromutilin; Anti-Bacterial Agents/administration & dosage/adverse effects/therapeutic use; Diterpenes/administration & dosage/adverse effects/therapeutic use; Linezolid/adverse effects/therapeutic use; Moxifloxacin/administration & dosage/adverse effects/therapeutic use; Pneumonia Bacterial/drug therapy/metabolism; Polycyclic Compounds/administration & dosage/adverse effects/therapeutic use; Thioglycolates/administration & dosage/adverse effects/therapeutic use

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Pages

1856-1867

Issue

11

Volume

69

ISSN

1537-6591 1058-4838 1058-4838

Update Year & Number

Hospital List

Citation

File TM; Goldberg L; Das A; Sweeney C; Saviski J; Gelone SP; Seltzer E; Paukner S; Wicha WW; Talbot GH; Gasink LB, “Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial.,” NEOMED Bibliography Database, accessed June 13, 2021, https://neomed.omeka.net/items/show/11412.

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