A Prospective, Randomized, Double-Blind, Multicenter, Phase 3 Study to Assess the Safety and Efficacy of Intravenous Ceftolozane/Tazobactam Compared With Meropenem in Adult Patients With Ventilated Nosocomial Pneumonia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 726
- 主要终点
- Percentage of Participants With All Cause Mortality in the Intent-to-Treat (ITT) Population - Day 28
研究概览
简要总结
This is a phase 3, multicenter, prospective, randomized study of intravenous (IV) ceftolozane/tazobactam versus IV meropenem in the treatment of adult participants with either ventilator-associated bacterial pneumonia (VABP) or ventilated hospital-acquired bacterial pneumonia (HABP). The primary objective is to demonstrate the non-inferiority of ceftolozane/tazobactam versus meropenem in adult participants with ventilated nosocomial pneumonia (VNP) based on the difference in Day 28 all-cause mortality rates in the Intent-to-treat (ITT) population using a non-inferiority margin of 10%.
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
- •Adult participants diagnosed with either VABP or ventilated HABP requiring IV antibiotic therapy;
- •Intubated and on mechanical ventilation at the time of randomization;
- •New or progressive infiltrate on chest radiography consistent with pneumonia;
- •Presence of clinical criteria consistent with a diagnosis of ventilated nosocomial pneumonia.
排除标准
- •History of moderate or severe hypersensitivity reactions to beta-lactam antibiotics;
- •Prior non-study antibiotics for > 24 hours;
- •Gram stain of lower respiratory tract specimen showing only gram positive bacteria;
- •Active immunosuppression;
- •End-stage renal disease or requirement for dialysis;
- •Expected survival < 72 hours;
- •Severe confounding respiratory condition (i.e., chest trauma with paradoxical respiration);
- •Known or suspected community-acquired bacterial pneumonia.
- •Anticipated concomitant use of any of the following medications during the course of study therapy: valproic acid or divalproex sodium. Anticipated concomitant use of serotonin re-uptake inhibitors, tricyclic antidepressants, or serotonin 5-HT1 receptor agonists (triptans), meperidine, or buspirone during the course of linezolid treatment.
- •Receipt of a monoamine oxidase inhibitor within 14 days prior to the first dose of study drug or anticipated concomitant use during the course of linezolid therapy.
研究组 & 干预措施
Meropenem
Participants receive 1000 mg meropenem IV every 8 hours for 8-14 days.
干预措施: Meropenem (Drug)
Ceftolozane/tazobactam
Participants receive 3000 mg ceftolozane/tazobactam intravenous IV (comprising 2000 mg ceftolozane and 1000 mg tazobactam) every 8 hours for 8-14 days.
干预措施: Ceftolozane/tazobactam (Drug)
结局指标
主要结局
Percentage of Participants With All Cause Mortality in the Intent-to-Treat (ITT) Population - Day 28
时间窗: Day 28
To demonstrate the non-inferiority of ceftolozane/tazobactam versus meropenem in stratified adult participants with ventilated nosocomial pneumonia (VNP) (participants with either ventilator-associated bacterial pneumonia \[VABP\] or ventilated hospital-acquired bacterial pneumonia \[HABP\]) based on the difference in all-cause mortality rates in the intent to treat (ITT) population using a non-inferiority margin of 10%. The estimated adjusted percentage was a weighted average across all strata, constructed using Mehrotra-Railkar continuity-corrected minimum risk (MRc) stratum weights.
次要结局
- Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Intent-to-Treat (ITT) Population(7 to 14 days after last dose of study drug (Up to ~Day 30))
- Percentage of Participants With All Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population - Day 28(Day 28)
- Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population(7 to 14 days after last dose of study drug (Up to ~Day 30))
- Percentage of Participants With Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the Test-of-Cure (TOC) Visit in the Microbiologically Evaluable (ME) Population (>=10 Isolates at Baseline)(7 to 14 days after last dose of study drug (Up to ~Day 30))
- Percentage of Participants With Per-Participant Microbiological Response of Cure or Presumed Cure at the End-of-Therapy (EOT) Visit in the Microbiologically Evaluable (ME) Population(Within 24 hours after last dose of study drug (Up to ~Day 15))
- Percentage of Participants With Per-Participant Microbiological Response of Cure or Presumed Cure at the Test-of-Cure (TOC) Visit in the Microbiologically Evaluable (ME) Population(7 to 14 days after last dose of study drug (Up to ~Day 30))
- Percentage of Participants With All-Cause Mortality in the Intent-to-Treat (ITT) Population - Day 14(Day 14)
- Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population(Within 24 hours after last dose of study drug (Up to ~Day 15))
- Percentage of Participants Who Report 1 or More Adverse Event (AE)(Up to 35 days after last dose of study drug (Up to ~Day 50))
- Percentage of Participants With Clinical Response of Clinical Cure at the Late Follow-up (LFU) Visit in the Clinically Evaluable (CE) Population(28 to 35 days after the last dose of study drug (Up to ~Day 50))
- Percentage of Participants With Any Serious Adverse Event (SAE)(Up to 35 days after last dose of study drug (Up to ~Day 50))
- Percentage of Participants Discontinuing Study Drug Due to an Adverse Event (AE)(Up to 14 days after the first dose of study drug (Up to ~Day 15))