TY - JOUR
T1 - A randomised, double-blind, phase 3 study comparing the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem for complicated intra-abdominal infections in hospitalised adults in Asia
AU - Qin, Xinyu
AU - Tran, Binh Giang
AU - Kim, Min Ja
AU - Wang, Lie
AU - Nguyen, Dung Anh
AU - Chen, Qian
AU - Song, Jie
AU - Laud, Peter J.
AU - Stone, Gregory G.
AU - Chow, Joseph W.
N1 - Funding Information:
The authors would like to thank the patients, their families and all investigators involved in this study. The authors also thank Niwat Montreewasuwat for involvement in data collection and analysis. Medical writing support, including assisting authors with the development of the outline and initial draft, incorporation of comments, fact checking, referencing, figure preparation, proofreading and submission, was provided by Catherine Savage, PhD, and editorial support, including fact checking and proofreading was provided by Valerie Moss, PhD, CMPP, both of Prime (Knutsford, UK) supported by AstraZeneca and Pfizer according to Good Publication Practice guidelines (http://annals.org/aim/article/2424869/good-publication-practice-communicating-company-sponsored-medical-research-gpp3). Ceftazidime/avibactam is being developed by Pfizer and Allergan Inc. The study sponsor (AstraZeneca) managed data collection and analysed the data. All authors had full access to all trial data and take responsibility for the integrity of the data and the accuracy of the data analysis.
Publisher Copyright:
© 2017 The Authors
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Ceftazidime/avibactam comprises the broad-spectrum cephalosporin ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam. This phase 3, randomised, double-blind study (NCT01726023) assessed the efficacy and safety of ceftazidime/avibactam plus metronidazole compared with meropenem in patients with complicated intra-abdominal infection (cIAI) in Asian countries. Subjects aged 18–90 years and hospitalised with cIAI requiring surgical intervention were randomised 1:1 to receive every 8 h either: ceftazidime/avibactam (2000/500 mg, 2-h infusion) followed by metronidazole (500 mg, 60-min infusion); or meropenem (1000 mg, 30-min infusion). Non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was concluded if the lower limit of the 95% confidence interval (CI) for the between-group difference in clinical cure rate was greater than −12.5% at the test-of-cure (TOC) visit (28–35 days after randomisation) in the clinically evaluable (CE) population. Safety was also evaluated. Of 441 subjects randomised, 432 received at least one dose of study medication (ceftazidime/avibactam plus metronidazole, n = 215; meropenem, n = 217). In the CE population at the TOC visit, non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was demonstrated, with clinical cure reported for 93.8% (166/177) and 94.0% (173/184) of subjects, respectively (between-group difference, −0.2, 95% CI −5.53 to 4.97). The clinical cure rate with ceftazidime/avibactam plus metronidazole was comparable in subjects with ceftazidime-non-susceptible and ceftazidime-susceptible isolates (95.7% vs. 92.1%, respectively). Adverse events were similar between the study groups. Ceftazidime/avibactam plus metronidazole was non-inferior to meropenem in the treatment of cIAIs in Asian populations and was effective against ceftazidime-non-susceptible pathogens. No new safety concerns were identified.
AB - Ceftazidime/avibactam comprises the broad-spectrum cephalosporin ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam. This phase 3, randomised, double-blind study (NCT01726023) assessed the efficacy and safety of ceftazidime/avibactam plus metronidazole compared with meropenem in patients with complicated intra-abdominal infection (cIAI) in Asian countries. Subjects aged 18–90 years and hospitalised with cIAI requiring surgical intervention were randomised 1:1 to receive every 8 h either: ceftazidime/avibactam (2000/500 mg, 2-h infusion) followed by metronidazole (500 mg, 60-min infusion); or meropenem (1000 mg, 30-min infusion). Non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was concluded if the lower limit of the 95% confidence interval (CI) for the between-group difference in clinical cure rate was greater than −12.5% at the test-of-cure (TOC) visit (28–35 days after randomisation) in the clinically evaluable (CE) population. Safety was also evaluated. Of 441 subjects randomised, 432 received at least one dose of study medication (ceftazidime/avibactam plus metronidazole, n = 215; meropenem, n = 217). In the CE population at the TOC visit, non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was demonstrated, with clinical cure reported for 93.8% (166/177) and 94.0% (173/184) of subjects, respectively (between-group difference, −0.2, 95% CI −5.53 to 4.97). The clinical cure rate with ceftazidime/avibactam plus metronidazole was comparable in subjects with ceftazidime-non-susceptible and ceftazidime-susceptible isolates (95.7% vs. 92.1%, respectively). Adverse events were similar between the study groups. Ceftazidime/avibactam plus metronidazole was non-inferior to meropenem in the treatment of cIAIs in Asian populations and was effective against ceftazidime-non-susceptible pathogens. No new safety concerns were identified.
KW - Asia
KW - Ceftazidime/avibactam
KW - Complicated intra-abdominal infection
KW - Efficacy
KW - Phase 3
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=85017371968&partnerID=8YFLogxK
U2 - 10.1016/j.ijantimicag.2017.01.010
DO - 10.1016/j.ijantimicag.2017.01.010
M3 - Article
C2 - 28363526
AN - SCOPUS:85017371968
SN - 0924-8579
VL - 49
SP - 579
EP - 588
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 5
ER -
