2519. 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
Authors: Li Junjie , Wei Feng , Xiang Peng , Tang Zhengang , Ding Lianshu , Losada Maria C , Iamboliyska Zlatka , Zhu Mingfen , Guo Xiaodan , Du Xiaoling , Chen Chang , Chen Luke Francis , Zhou Min , Qu Jieming 
Published: November 2023

Abstract

Background
Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. In these patients, there is an unmet need for effective antimicrobial therapy. This study enrolled participants mainly from China to support the regional use of imipenem/cilastatin/relebactam (IMI/REL). The aim of the study was to assess the efficacy and safety of IMI/REL compared with piperacillin/tazobactam (PIP/TAZ) for the treatment of HABP/VABP.

Methods
This study was a Phase 3, randomized trial conducted in 8 countries (NCT03583333). Participants 18–90 years of age with HABP/VABP requiring intravenous (IV) antibiotic treatment were randomized 1:1 to receive either IV IMI/REL (500 mg IMI/250 mg REL) or PIP/TAZ (4000 mg/500 mg) administered every 6 h for 7–14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (excluding patients with only gram-positive cocci at baseline). Secondary endpoints included clinical response rate, microbiological response rate and adverse events (AEs).

Results
In total, 270 patients (IMI/REL, N=134; PIP/TAZ, N=136) were included in the MITT population, with 201 patients from mainland China (IMI/REL, N=106; PIP/TAZ, N=100). Demographics and baseline characteristics were generally comparable for both treatment groups in the MITT population, with the exception of preexisting cerebrovascular conditions which were higher in IMI/REL vs PIP/TAZ group. The median age (range) was 60.0 (19–87) years and 73.3% were male (Table 1). In the MITT population, IMI/REL was non-inferior to PIP/TAZ for day 28 all-cause mortality (11.2% vs 5.9%; adjusted difference [95%CI]: 5.2% [-1.5%, 12.4%],P&lt; 0.024). Results for key secondary endpoints were comparable between treatment groups (Table 2). Overall, the incidence of AEs was comparable between IMI/REL vs PIP/TAZ (Table 3).

Conclusion
In a patient population mainly from China, IMI/REL was non-inferior to PIP/TAZ for the treatment of HABP/VABP assessed by the endpoint of day 28 all-cause mortality and was associated with favorable outcomes regarding clinical and microbiological response.IMI/REL was well tolerated and had a safety profile comparable to PIP/TAZ.

Disclosures
Maria C. Losada, BA, Merck & Co., Inc., Rahway, New Jersey, USA: Employee|Merck & Co., Inc., Rahway, New Jersey, USA: Stocks/Bonds|Merck & Co., Inc., Rahway, New Jersey, USA: Stocks/Bonds Zlatka Iamboliyska, MD, MSD China: Employee|MSD China: Stocks/Bonds Mingfen Zhu, MD, MSD China: Employee|MSD China: Stocks/Bonds Xiaodan Guo, MD, MSD China: Employee|MSD China: Stocks/Bonds Xiaoling Du, n/a, MSD China: Employee|MSD China: Stocks/Bonds Chang Chen, MD, MSD China: Employee|MSD China: Stocks/Bonds Luke Francis Chen, MD, Merck & Co., Inc., Rahway, New Jersey, USA: Employee|Merck & Co., Inc., Rahway, New Jersey, USA: Stocks/Bonds