A phase III randomized controlled non-inferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) versus piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP).
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
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引用次数: 0
Abstract
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 non-inferior 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 non-inferiority criteria versus 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.
期刊介绍:
International Journal of Infectious Diseases (IJID)
Publisher: International Society for Infectious Diseases
Publication Frequency: Monthly
Type: Peer-reviewed, Open Access
Scope:
Publishes original clinical and laboratory-based research.
Reports clinical trials, reviews, and some case reports.
Focuses on epidemiology, clinical diagnosis, treatment, and control of infectious diseases.
Emphasizes diseases common in under-resourced countries.