A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP)
Objectives: Imipenem/cilastatin/relebactam (IMI/REL) is a β-lactam/β-lactamase inhibitor combination effective against gram-negative pathogens. Efficacy and safety of IMI/REL were studied in critically ill adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pn...
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Elsevier
2025-04-01
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| Series: | International Journal of Infectious Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1201971224004326 |
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| author | Junjie Li Feng Wei Peng Xiang Zhengang Tang Lianshu Ding Luke Francis Chen Maria Losada Zlatka Iamboliyska Fang Sun Mingfen Zhu Xiaodan Guo Xiaoling Du Chang Chen Christopher Bruno Sandra Koseoglu Katherine Young Min Zhou Jieming Qu |
| author_facet | Junjie Li Feng Wei Peng Xiang Zhengang Tang Lianshu Ding Luke Francis Chen Maria Losada Zlatka Iamboliyska Fang Sun Mingfen Zhu Xiaodan Guo Xiaoling Du Chang Chen Christopher Bruno Sandra Koseoglu Katherine Young Min Zhou Jieming Qu |
| author_sort | Junjie Li |
| collection | DOAJ |
| description | Objectives: Imipenem/cilastatin/relebactam (IMI/REL) is a β-lactam/β-lactamase inhibitor combination effective against gram-negative pathogens. Efficacy and safety of IMI/REL were studied in critically ill adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). Methods: In this phase III, double-blind, multinational, randomized trial (NCT03583333), adults with HABP/VABP were randomized 1:1 to receive intravenous IMI/REL (500 mg/250 mg) or piperacillin/tazobactam (PIP/TAZ; 4000 mg/500 mg) every 6 h for 7-14 days. The primary endpoint was 28-day all-cause mortality (ACM). Secondary endpoints were clinical response (CR), microbiological response (MR), and adverse event (AE) incidence. Results: In the modified intention-to-treat population (N = 270 [IMI/REL: n = 134; PIP/TAZ: n = 136]), demographics and baseline characteristics were comparable between treatment groups. Most patients were from China. IMI/REL was noninferior to PIP/TAZ for 28-day ACM (11.2% vs 5.9%; adjusted difference [95% confidence interval]: 5.2% [−1.5 to 12.4]). Secondary outcomes were comparable between treatment groups, including favorable CR and MR. AEs resulting in death were generally consistent with pre-existing or underlying illness. Conclusions: IMI/REL met noninferiority criteria vs PIP/TAZ for 28-day ACM, and safety profiles were comparable. This trial could support the use of IMI/REL to treat adults with HABP/VABP, including regional use in China. |
| format | Article |
| id | doaj-art-19044a097f6c4ce2b76527463c51de01 |
| institution | Kabale University |
| issn | 1201-9712 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj-art-19044a097f6c4ce2b76527463c51de012025-01-23T05:26:28ZengElsevierInternational Journal of Infectious Diseases1201-97122025-04-01153107357A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP)Junjie Li0Feng Wei1Peng Xiang2Zhengang Tang3Lianshu Ding4Luke Francis Chen5Maria Losada6Zlatka Iamboliyska7Fang Sun8Mingfen Zhu9Xiaodan Guo10Xiaoling Du11Chang Chen12Christopher Bruno13Sandra Koseoglu14Katherine Young15Min Zhou16Jieming Qu17Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Institute of Respiratory Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, The First People's Hospital of Nanning, Nanning, ChinaDepartment of Neurosurgery, Changsha Central Hospital, Changsha, Hunan, ChinaDepartment of Neurosurgery, Shiyan Renmin Hospital, Hubei University of Medicine, Shiyan, ChinaDepartment of Neurosurgery, The Affiliated Huai'an First Hospital of Nanjing Medical University, Huai'an, ChinaMerck & Co., Inc., Rahway, New Jersey, USAMerck & Co., Inc., Rahway, New Jersey, USAMerck & Co., Inc., Rahway, New Jersey, USAMSD (China) Co., Ltd., Shanghai, ChinaMSD (China) Co., Ltd., Shanghai, ChinaMSD (China) Co., Ltd., Beijing, ChinaMSD (China) Co., Ltd., Shanghai, ChinaMSD (China) Co., Ltd., Beijing, ChinaMerck & Co., Inc., Rahway, New Jersey, USAMerck & Co., Inc., Rahway, New Jersey, USAMerck & Co., Inc., Rahway, New Jersey, USADepartment of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Corresponding author: Jieming Qu, No. 197 Rujin 2nd Road, Huangpu District, Shanghai, China.Objectives: Imipenem/cilastatin/relebactam (IMI/REL) is a β-lactam/β-lactamase inhibitor combination effective against gram-negative pathogens. Efficacy and safety of IMI/REL were studied in critically ill adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). Methods: In this phase III, double-blind, multinational, randomized trial (NCT03583333), adults with HABP/VABP were randomized 1:1 to receive intravenous IMI/REL (500 mg/250 mg) or piperacillin/tazobactam (PIP/TAZ; 4000 mg/500 mg) every 6 h for 7-14 days. The primary endpoint was 28-day all-cause mortality (ACM). Secondary endpoints were clinical response (CR), microbiological response (MR), and adverse event (AE) incidence. Results: In the modified intention-to-treat population (N = 270 [IMI/REL: n = 134; PIP/TAZ: n = 136]), demographics and baseline characteristics were comparable between treatment groups. Most patients were from China. IMI/REL was noninferior to PIP/TAZ for 28-day ACM (11.2% vs 5.9%; adjusted difference [95% confidence interval]: 5.2% [−1.5 to 12.4]). Secondary outcomes were comparable between treatment groups, including favorable CR and MR. AEs resulting in death were generally consistent with pre-existing or underlying illness. Conclusions: IMI/REL met noninferiority criteria vs PIP/TAZ for 28-day ACM, and safety profiles were comparable. This trial could support the use of IMI/REL to treat adults with HABP/VABP, including regional use in China.http://www.sciencedirect.com/science/article/pii/S1201971224004326Gram-negative bacteriaMultidrug resistanceNosocomial infectionPneumonia |
| spellingShingle | Junjie Li Feng Wei Peng Xiang Zhengang Tang Lianshu Ding Luke Francis Chen Maria Losada Zlatka Iamboliyska Fang Sun Mingfen Zhu Xiaodan Guo Xiaoling Du Chang Chen Christopher Bruno Sandra Koseoglu Katherine Young Min Zhou Jieming Qu A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) International Journal of Infectious Diseases Gram-negative bacteria Multidrug resistance Nosocomial infection Pneumonia |
| title | A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) |
| title_full | A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) |
| title_fullStr | A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) |
| title_full_unstemmed | A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) |
| title_short | A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) |
| title_sort | phase iii randomized controlled noninferiority trial to study the efficacy and safety of imipenem cilastatin relebactam imi rel vs piperacillin tazobactam pip taz in patients with hospital acquired bacterial pneumonia habp or ventilator associated bacterial pneumonia vabp |
| topic | Gram-negative bacteria Multidrug resistance Nosocomial infection Pneumonia |
| url | http://www.sciencedirect.com/science/article/pii/S1201971224004326 |
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