A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Subjects With Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 537
- 主要终点
- Percentage of Participants With All-cause Mortality (ACM) Through Day 28 in the Modified Intention-to-treat (MITT) Population
研究概览
简要总结
This study aims to compare treatment with a fixed-dose combination (FDC) of imipenem/relebactam/cilastatin (IMI/REL) with a FDC of piperacillin/tazobactam (PIP/TAZ) in participants with hospital-acquired or ventilator-associated bacterial pneumonia (HABP or VAPB, respectively). The primary hypothesis is that IMI/REL is non-inferior to PIP/TAZ in the incidence rate of all-cause mortality.
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
- Double (Participant, 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
- •Requires treatment with IV antibiotic therapy for hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP)
- •Fulfills clinical and radiographic criteria, with onset of criteria occurring after more than 48 hours of hospitalization or within 7 days after discharge from a hospital (for HABP); or at least 48 hours after mechanical ventilation (for VABP)
- •Has an adequate baseline lower respiratory tract specimen obtained for Gram stain and culture
- •Has an infection known or thought to be caused by microorganisms susceptible to the IV study therapy
- •Agrees to allow any bacterial isolates obtained from protocol-required specimens related to the current infection to be provided to the Central Microbiology Reference Laboratory for study-related microbiological testing, long term storage, and other future testing
- •Is not of reproductive potential; or if of reproductive potential agrees to avoid impregnating a partner or avoid becoming pregnant, by practicing abstinence or using acceptable contraception
排除标准
- •Has a baseline lower respiratory tract specimen Gram stain that shows the presence of Gram-positive cocci only
- •Has confirmed or suspected community-acquired bacterial pneumonia (CABP)
- •Has confirmed or suspected pneumonia of viral, fungal or parasitic origin
- •Has HABP/VABP caused by an obstructive process, including lung cancer or other known obstruction
- •Has a carcinoid tumor or carcinoid syndrome
- •Has active immunosuppression defined as either receiving immunosuppressive medications or having a medical condition associated with immunodeficiency
- •Is expected to survive for less than 72 hours
- •Has a concurrent condition or infection that would preclude evaluation of therapeutic response
- •Has received effective antibacterial drug therapy for the index infection of HABP/VABP for more than 24 hours continuously, during the previous 72 hours
- •Has a history of serious allergy, hypersensitivity or a serious reaction to any penicillin or beta-lactamase inhibitors
- •Female is pregnant, expecting to conceive, is breastfeeding or plans to breastfeed
- •Has a history of seizure disorder requiring ongoing prior treatment with anti-convulsive therapy within the last 3 years
- •Anticipates treatment with the following: valproic acid or divalproex sodium, serotonin re-uptake inhibitors, tricyclic antidepressants, or serotonin receptor antagonists, meperidine, buspirone, concomitant systemic antibacterial agents, antifungal or antiviral therapy for the index infection of HABP/VABP
- •Is currently undergoing hemodialysis or peritoneal dialysis
- •Is currently participating in, has participated in during the previous 30 days, or anticipates to participate in any other clinical study involving the administration of experimental medication
- •Has previously participated in this study
研究组 & 干预措施
IMI/REL
Imipenem 500 mg + relebactam 250 mg + cilastatin 500 mg as a FDC administered intravenously (IV) every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.
干预措施: Cilastatin (Drug)
IMI/REL
Imipenem 500 mg + relebactam 250 mg + cilastatin 500 mg as a FDC administered intravenously (IV) every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.
干预措施: Imipenem (Drug)
IMI/REL
Imipenem 500 mg + relebactam 250 mg + cilastatin 500 mg as a FDC administered intravenously (IV) every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.
干预措施: Relebactam (Drug)
IMI/REL
Imipenem 500 mg + relebactam 250 mg + cilastatin 500 mg as a FDC administered intravenously (IV) every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.
干预措施: Linezolid (Drug)
PIP/TAZ
Piperacillin 4000 mg + tazobactam 500 mg as a FDC administered IV every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.
干预措施: Piperacillin (Drug)
PIP/TAZ
Piperacillin 4000 mg + tazobactam 500 mg as a FDC administered IV every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.
干预措施: Tazobactam (Drug)
PIP/TAZ
Piperacillin 4000 mg + tazobactam 500 mg as a FDC administered IV every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.
干预措施: Linezolid (Drug)
结局指标
主要结局
Percentage of Participants With All-cause Mortality (ACM) Through Day 28 in the Modified Intention-to-treat (MITT) Population
时间窗: Up to 28 days
The percentage of participants in the MITT population with mortality due to any cause from randomization through Day 28 was determined for each arm.
次要结局
- Percentage of Participants in the MITT Population With a Favorable Clinical Response (FCR) at Early Follow-up (EFU) Visit(Up to 16 days after end of therapy (up to 30 days))
- Percentage of Participants Discontinuing Study Therapy Due to an AE(Up to 14 days)
- Percentage of Participants With ACM in the Microbiological Modified Intention-to-treat (mMITT) Population(Up to 28 days)
- Percentage of Participants in the Clinically Evaluable (CE) Population With a FCR at On-therapy Visit 1 (OTX1) [Day 3](Day 3 (OTX1))
- Percentage of Participants in the MITT Population With a FCR at OTX3 (Day 10)(Day 10 (OTX3))
- Percentage of Participants With ≥1 Adverse Event (AE)(Up to 30 days)
- Percentage of Participants With ACM at EFU in the MITT Population(Up to 16 days after end of therapy (up to 30 days))
- Percentage of Participants in the CE Population With a FCR at OTX3 (Day 10)(Day 10 (OTX3))
- Percentage of Participants in the CE Population With a FCR at EOT Visit(From Day 7 to Day 14)
- Percentage of Participants in the CE Population With a FCR at Day 28(Day 28)
- Percentage of Participants in the MITT Population With a FCR at OTX1 (Day 3)(Day 3 (OTX1))
- Percentage of Participants in the MITT Population With a FCR at OTX2 (Day 6)(Day 6 (OTX2))
- Percentage of Participants in the mMITT Population With a Favorable Microbiological Response (FMR) at End of Treatment (EOT) Visit(From Day 7 to Day 14)
- Percentage of Participants With ACM at EFU in the mMITT Population(Up to 16 days after end of therapy (up to 30 days))
- Percentage of Participants in the CE Population With a FCR at OTX2 (Day 6)(Day 6 (OTX2))
- Percentage of Participants in the MITT Population With a FCR at Day 28(Day 28)
- Percentage of Participants in the Microbiologically Evaluable (ME) Population With a FMR at EOT Visit(From Day 7 to Day 14)
- Percentage of Participants in the ME Population With a FMR at EFU Visit(Up to 16 days after end of therapy (up to Day 30))
- Percentage of Participants in the CE Population With a FCR at EFU Visit(Up to 16 days after end of therapy (up to Day 30))
- Percentage of Participants in the MITT Population With a FCR at EOT(From Day 7 to Day 14)
- Percentage of Participants in the mMITT Population With a FMR at EFU Visit(Up to 16 days after end of therapy (up to Day 30))