A Multicenter, Randomized, Double-blind, Parallel-group, Clinical Study of S-649266 Compared With Meropenem for the Treatment of Hospital-acquired Bacterial Pneumonia, Ventilator-associated Bacterial Pneumonia, or Healthcare-associated Bacterial Pneumonia Caused by Gram-negative Pathogens
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- All-cause Mortality Rate at Day 14
研究概览
简要总结
The primary objective of this study is to compare all-cause mortality at Day 14 in participants receiving cefiderocol with participants receiving the comparator, meropenem, in adults with hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or healthcare-associated bacterial pneumonia (HCABP) caused by Gram-negative pathogens.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Subjects 18 years or older at the time of signing informed consent
- •Subjects who have provided written informed consent or their informed consent has been provided by a legally authorized representative
- •Subjects who meet the clinical diagnosis criteria for hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or healthcare-associated bacterial pneumonia (HCABP)
- •All subjects must fulfill at least 1 of the following clinical criteria at screening:
- •New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea, tachypnea (eg, respiratory rate > 25 breaths/minute), expectorated sputum production, or requirement for mechanical ventilation
- •Hypoxemia (eg, a partial pressure of oxygen [PaO2] < 60 mm Hg while the subject is breathing room air, as determined by arterial blood gas [ABG], or worsening of the ratio of the PaO2 to the fraction of inspired oxygen [PaO2/FiO2])
- •Need for acute changes in the ventilator support system to enhance oxygenation, as determined by worsening oxygenation (ABG or PaO2/FiO2) or needed changes in the amount of positive end-expiratory pressure
- •New onset of or increase in (quantity or characteristics) suctioned respiratory secretions, demonstrating evidence of inflammation and absence of contamination
- •All subjects must have at least 1 of the following signs:
- •Documented fever (ie, core body temperature [tympanic, rectal, esophageal] ≥ 38°C [100.4°F], oral temperature ≥ 37.5°C, or axillary temperature ≥ 37°C)
- •Hypothermia (ie, core body temperature [tympanic, rectal, esophageal] ≤ 35°C [95.0°F], oral temperature ≤ 35.5°C and axillary temperature ≤ 36°C)
- •Leukocytosis with a total peripheral white blood cell (WBC) count ≥ 10,000 cells/mm³
- •Leukopenia with total peripheral WBC count ≤ 4500 cells/mm³
- •Greater than 15% immature neutrophils (bands) noted on peripheral blood smear
- •All subjects must have a chest radiograph during screening showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia. A computed tomography (CT) scan in the same time window showing the same findings could also be acceptable
- •All subjects must have a suspected Gram-negative infection involving the lower respiratory tract
排除标准
- •Subjects who have known or suspected community-acquired bacterial pneumonia (CABP), atypical pneumonia, viral pneumonia, or chemical pneumonia (including aspiration of gastric contents, inhalation injury)
- •Other exclusions based on the prescribing information of meropenem or linezolid, prior antibiotic usage, age, and pregnancy.
研究组 & 干预措施
Cefiderocol
Participants will receive 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
干预措施: Cefiderocol (Drug)
Cefiderocol
Participants will receive 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
干预措施: Linezolid (Drug)
Meropenem
Participants will receive 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
干预措施: Meropenem (Drug)
Meropenem
Participants will receive 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
干预措施: Linezolid (Drug)
结局指标
主要结局
All-cause Mortality Rate at Day 14
时间窗: From first dose of study drug to Day 14
The all-cause mortality (ACM) rate at Day 14 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from the first infusion of study drug up to Day 14. The Modified Intent-to-Treat Population included all randomized participants who met either of the following criteria: * Evidence of Gram-negative infection of the lower respiratory tract based on a culture, Gram-stain, or other diagnostic test * Evidence of a lower respiratory tract infection but culture or other diagnostic tests did not provide a microbiologic diagnosis
次要结局
- Percentage of Participants With Microbiologic Eradication at Early Assessment(Early Assessment, Days 3 to 4)
- Percentage of Participants With Clinical Cure at Test of Cure(Test of cure (7 days after the end of treatment; equivalent to Study Day 14 to 21))
- Percentage of Participants With Clinical Cure at Early Assessment (EA)(Early assessment (Day 3-4 after the start of treatment))
- Percentage of Participants With Microbiologic Eradication at End of Treatment(End of treatment, Day 7 to 14)
- Percentage of Participants With Clinical Cure at End of Treatment (EOT)(End of treatment (Day 7 to 14))
- All-cause Mortality Rate at the End of Study(From first dose of study drug through end of study (28 days after end of treatment, up to 42 days))
- Number of Participants With Treatment-Emergent Adverse Events(From first dose of study drug through the end of study, up to 42 days.)
- Total Hospitalization Time(From first dose of study drug to test of cure (7 days after end of treatment; equivalent to Study Day 14 to 21) and to follow-up (14 days after the end of treatment; Day 21 to 28))
- All-cause Mortality Rate at Day 28(From first dose of study drug to Day 28)
- Percentage of Participants With Microbiologic Eradication at Test of Cure (TOC)(Test of cure (7 days after end of treatment; equivalent to Study Day 14 to 21))
- Percentage of Participants With Sustained Clinical Cure at Follow-up (FU)(Follow-up (14 days after the end of treatment; Day 21 to 28))
- Percentage of Participants With Sustained Microbiologic Eradication at Follow-up(Follow-up (14 days after the end of treatment, Days 21 to 28))