A Multi-national Phase 3, 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
- 274
- 试验地点
- 68
- 主要终点
- Percentage of Participants With All-cause Mortality Through Day 28 in the Modified Intent to Treat (MITT) Population
研究概览
简要总结
This study will evaluate the efficacy and safety of a FDC of imipenem/cilastatin (IMI) and relebactam (REL) [IMI/REL, MK-7655A] compared to piperacillin/tazobactam (PIP/TAZ) in the treatment of adults diagnosed with Hospital-Acquired Bacterial Pneumonia (HABP) or Ventilator-Associated Bacterial Pneumonia (VABP). The primary hypothesis is that IMI/REL is non-inferior to PIP/TAZ as measured by the incidence rate of all-cause mortality through Day 28 post-randomization.
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 90 Years（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 HABP or VABP
- •Fulfills clinical and radiographic criteria within 48 hours prior to randomization, with onset of criteria occurring after more than 2 days of hospitalization or within 7 days after discharge from a hospital for HABP; or at least 2 days after mechanical ventilation (for VABP)
- •Has an adequate baseline (at or within 2 days of screening) lower respiratory tract specimen obtained for Gram stain and culture
- •Has an infection known or thought to be, in the opinion of the investigator, 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 and long-term storage
- •Males agree to use contraception as detailed in protocol from the time of providing informed consent through completion of the study and refrain from donating sperm during this period
- •Females are not pregnant, not breastfeeding, and are either: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive guidance from the time of providing informed consent through completion of the study
- •If a penicillin skin test is required by local clinical practice, the participant must have a negative skin test result for allergy to penicillin
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 caused by Mycoplasma, Chlamydia, or Legionella, or of viral, fungal, or parasitic etiology
- •Has HABP/VABP caused by an obstructive process, including lung cancer (or other malignancy metastatic to the lungs resulting in pulmonary obstruction) or other known obstruction
- •Has a carcinoid tumor or carcinoid syndrome
- •Has active immunosuppression
- •Is expected to die during the 7- to 14-day treatment period, despite adequate antibiotic therapy
- •Has a concurrent condition or infection that, in the investigator's judgment, would preclude evaluation of therapeutic response
- •Has a history of serious allergy, hypersensitivity, or any serious reaction to any β-lactams or β-lactamase inhibitors
- •Has a history of a seizure disorder which has required ongoing treatment with anticonvulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years
- •Is currently undergoing hemodialysis or peritoneal dialysis
- •A WOCBP who has a positive urine pregnancy test at screening
- •Has received effective antibacterial drug therapy with known coverage of pathogens that cause HABP/VABP for a continuous duration of more than 48 hours during the previous 72 hours
- •Is anticipated to be treated with any of the prohibited medications during the course of study therapy
- •Is currently participating in, or has participated in, any other clinical study involving the administration of investigational or experimental medication (not licensed by regulatory agencies) at the time of the presentation or during the previous 90 days prior to screening or is anticipated to participate in such a clinical study during the course of this trial
- •Has previously participated in this study at any time
研究组 & 干预措施
IMI/REL FDC
Imipenem/cilastatin/relebactam (IMI/REL) administered intravenously (IV) as a fixed-dose combination (FDC) at a dosage of 500 mg IMI/250 mg REL, once every 6 hours for a minimum 7 days, up to 14 days. At the start of IMI/REL treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total.
干预措施: IMI/REL FDC (Drug)
IMI/REL FDC
Imipenem/cilastatin/relebactam (IMI/REL) administered intravenously (IV) as a fixed-dose combination (FDC) at a dosage of 500 mg IMI/250 mg REL, once every 6 hours for a minimum 7 days, up to 14 days. At the start of IMI/REL treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total.
干预措施: Linezolid (Drug)
PIP/TAZ FDC
Piperacillin/tazobactam (PIP/TAZ ) administered IV as a FDC at a dosage of 4000 mg PIP/500 mg TAZ once every 6 hours for a minimum 7 days, up to 14 days. At the start of PIP/TAZ treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total.
干预措施: PIP/TAZ FDC (Drug)
PIP/TAZ FDC
Piperacillin/tazobactam (PIP/TAZ ) administered IV as a FDC at a dosage of 4000 mg PIP/500 mg TAZ once every 6 hours for a minimum 7 days, up to 14 days. At the start of PIP/TAZ treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total.
干预措施: Linezolid (Drug)
结局指标
主要结局
Percentage of Participants With All-cause Mortality Through Day 28 in the Modified Intent to Treat (MITT) Population
时间窗: Up to approximately 28 days
For each participant, survival status was assessed at Day 28 post-randomization and recorded on the electronic Case Report Form. The percentage of participants with all-cause mortality through Day 28 in the MITT population is presented.
次要结局
- Percentage of Participants Achieving a Favorable Clinical Response at Early Follow-up (EFU) Visit in the MITT Population(Up to approximately 27 days)
- Percentage of Participants Achieving a Favorable Clinical Response at EFU Visit in the Clinically Evaluable (CE) Population(Up to approximately 27 days)
- Percentage of Participants Achieving a Favorable Clinical Response at End of Therapy (EOT) Visit in the MITT Population(Up to approximately 14 days)
- Percentage of Participants Achieving a Favorable Clinical Response at EOT Visit in the Clinically Evaluable (CE) Population(Up to approximately 14 days)
- Percentage of Participants Achieving a Favorable Microbiological Response at EOT Visit in Microbiological Modified Intent-To-Treat Population (mMITT) Population(Up to approximately 14 days)
- Percentage of Participants Achieving a Favorable Microbiological Response at EFU Visit in Microbiological-evaluable (ME) Population.(Up to approximately 27 days)
- Percentage of Participants Achieving a Favorable Microbiological Response at EOT Visit in the ME Population(Up to approximately 14 days)
- Percentage of Participants Experiencing Adverse Events (AEs)(Up to approximately 98 days)
- Percentage of Participants Discontinuing Study Drug Due to AEs(Up to approximately 14 days)