Cargando…

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

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 reg...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10678407/
http://dx.doi.org/10.1093/ofid/ofad500.2137
_version_ 1785150354109759488
author 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
author_facet 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
author_sort Li, Junjie
collection PubMed
description 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). [Figure: see text] 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< 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). [Figure: see text] [Figure: see text] 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
format Online
Article
Text
id pubmed-10678407
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-106784072023-11-27 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 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 Open Forum Infect Dis 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). [Figure: see text] 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< 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). [Figure: see text] [Figure: see text] 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 Oxford University Press 2023-11-27 /pmc/articles/PMC10678407/ http://dx.doi.org/10.1093/ofid/ofad500.2137 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstract
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
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10678407/
http://dx.doi.org/10.1093/ofid/ofad500.2137
work_keys_str_mv AT lijunjie 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT weifeng 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT xiangpeng 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT tangzhengang 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT dinglianshu 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT losadamariac 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT iamboliyskazlatka 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT zhumingfen 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT guoxiaodan 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT duxiaoling 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT chenchang 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT chenlukefrancis 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT zhoumin 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia
AT qujieming 2519amultinationalphase3randomizeddoubleblindactivecomparatorcontrolledclinicaltrialtostudythesafetytolerabilityandefficacyofimipenemcilastatinrelebactammk7655aversuspiperacillintazobactaminsubjectswithhospitalacquiredbacterialpneumoniaorventilatorassocia