A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Lefamulin (BC 3781) Versus Moxifloxacin (With or Without Adjunctive Linezolid) in Adults With Community-Acquired Bacterial Pneumonia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 551
- 试验地点
- 99
- 主要终点
- Early Clinical Response (ECR)
研究概览
简要总结
This study evaluates the safety and efficacy of lefamulin, a pleuromutilin, for the treatment of adults with moderate to severe community-acquired bacterial pneumonia.
详细描述
Lefamulin is a potent, semi-synthetic antibacterial belonging to a novel class known as the pleuromutilins. Both the intravenous (IV) and oral dosage forms of lefamulin are under investigation in this study. Lefamulin's in vitro antibacterial profile includes the most important bacterial pathogens causing respiratory tract infection (RTI). The antibacterial spectrum comprises S. pneumoniae, H. influenzae, M. catarrhalis, the atypical respiratory pathogens L. pneumophila, C. pneumoniae, and M. pneumoniae, S. aureus including MRSA and CA-MRSA, ß-haemolytic streptococci including S. pyogenes and S. agalactiae, and Enterococcus faecium including vancomycin-resistant enterococci (VRE). Moreover, as demonstrated in cross-resistance studies, lefamulin remains active against clinical isolates resistant to the following antimicrobial(s) (classes): macrolides, lincosamides, streptogramin B, oxazolidinones, tetracyclines, ß lactams, quinolones, trimethoprim-sulfametoxazole, mupirocin, and vancomycin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be male or female at least 18 years of age.
- •Provide written informed consent and be willing and able to adhere to the study-specified procedures and restrictions.
- •Have an acute illness (7 days duration) with at least 3 of the following symptoms consistent with a lower respiratory tract infection (new or worsening):
- •New or increased cough
- •Purulent sputum production
- •Chest pain due to pneumonia
- •Have at least 2 of the following vital sign abnormalities:
- •Fever (body temperature >38.0°C (100.4°F) measured orally or equivalent temperature from an alternate body site) or hypothermia (body temperature <35.0°C (95.0°F) measured orally or equivalent temperature from an alternate body site)
- •Hypotension (systolic blood pressure <90 mmHg)
- •Tachycardia (heart rate >100 beats/min)
- •Tachypnea (respiratory rate >20 breaths/min)
- •Have at least 1 other clinical sign or laboratory finding of CABP:
- •Hypoxemia (i.e., O2 saturation <90% on room air or while receiving supplemental oxygen at subject's baseline requirement or PaO2 <60 mmHg)
- •Auscultatory and/or percussion findings consistent with pneumonia (e.g., crackles, egophony, dullness)
- •White blood cell (WBC) count >10,000 cells/mm3 or <4500 cells/mm3 or >15% immature neutrophils (bands) regardless of total WBC count
- •Have radiographically-documented pneumonia within 48 hours before enrollment (i.e., infiltrates in a lobar or multilobar distribution or diffuse opacities on chest x-ray or chest computed tomography scan consistent with acute bacterial pneumonia).
- •Have a Pneumonia Outcomes Research Team (PORT) Risk Class ≥III.
排除标准
- •Have received more than a single dose of a short-acting oral or IV antibacterial for CABP within 72 hours before randomization
- •Require concomitant systemic antibacterial therapy potentially effective against CABP pathogens
- •Have been hospitalized for 2 or more days within 90 days prior to the onset of symptoms or have resided in a nursing home or long-term healthcare facility within 30 days prior to the onset of symptoms. NOTE: Residence in an independent living facility is permitted.
- •Have confirmed or suspected CABP caused by a pathogen known to be resistant to any of the study drugs (e.g., Pseudomonas aeruginosa, any pathogen of the Enterobacteriaceae Family) or attributable to etiologies other than community acquired bacterial pathogens (e.g., ventilator associated pneumonia, hospital acquired bacterial pneumonia, bacterial aspiration pneumonia, Pneumocystis jiroveci pneumonia or other fungal pneumonia, viral or mycobacterial infection of the lung).
- •Have a noninfectious cause of pulmonary infiltrates (e.g., pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure, bronchial obstruction, lung cancer, cystic fibrosis).
- •Have confirmed or suspected pleural empyema (does not include sterile parapneumonic effusions).
- •Require mechanical ventilation.
研究组 & 干预措施
Lefamulin
Intravenous lefamulin with potential step-down to oral lefamulin
干预措施: lefamulin (Drug)
Moxifloxacin +/- Linezolid
Intravenous moxifloxacin with potential step-down to oral moxifloxacin +/- linezolid
干预措施: Moxifloxacin (Drug)
Moxifloxacin +/- Linezolid
Intravenous moxifloxacin with potential step-down to oral moxifloxacin +/- linezolid
干预措施: Linezolid (Drug)
结局指标
主要结局
Early Clinical Response (ECR)
时间窗: ECR was assessed 96 +/- 24 hours after the first dose of study drug.
ECR was defined as survival with improvement in at least 2 signs and symptoms of CABP (relative to baseline), no worsening of any CABP sign or symptom, and no use of concomitant antibiotics (other than adjunctive linezolid, as allowed by the study protocol) for the treatment of CABP through the ECR assessment.
次要结局
- Investigator's Assessment of Clinical Response (IACR)(IACR was assessed at the Test of Cure visit, 5 - 10 days after the last dose of study drug.)