Lefamulin efficacy and safety in a pooled phase 3 clinical trial population with community-acquired bacterial pneumonia and common clinical comorbidities
| Autor: | Christian Sandrock, Susanne Paukner, Thomas M. File, Anita Das, Elizabeth Alexander, Gregory J. Moran, Lisa Goldberg |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Respiratory System Moxifloxacin Phases of clinical research Administration Oral Pleuromutilin Comorbidity Cardiorespiratory Medicine and Haematology Cardiovascular 0302 clinical medicine 80 and over 030212 general & internal medicine Lung Aged 80 and over 0303 health sciences education.field_of_study Bacterial Middle Aged Anti-Bacterial Agents Infectious Diseases 6.1 Pharmaceuticals Thioglycolates Administration Respiratory Administration Intravenous Female Diterpenes Intravenous Infection medicine.drug Fluoroquinolones Pulmonary and Respiratory Medicine Oral Adult medicine.medical_specialty Adolescent Population Clinical Trials and Supportive Activities Microbial Sensitivity Tests 03 medical and health sciences Young Adult Diseases of the respiratory system Double-Blind Method Clinical Research Internal medicine Diabetes mellitus medicine Pneumonia Bacterial Humans Polycyclic Compounds education Asthma Aged RC705-779 030306 microbiology business.industry Prevention Research Bacterial pneumonia Antibiotic Evaluation of treatments and therapeutic interventions Pneumonia medicine.disease United States Good Health and Well Being Heart failure Clinical response business Lefamulin |
| Zdroj: | BMC Pulmonary Medicine, Vol 21, Iss 1, Pp 1-10 (2021) BMC Pulmonary Medicine BMC pulmonary medicine, vol 21, iss 1 |
| ISSN: | 1471-2466 |
| Popis: | Background Lefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management. Methods In LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin. Results Lefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference − 1.1%; 95% CI − 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified. Conclusions Lefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities. Trial registration ClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016). |
| Databáze: | OpenAIRE |
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