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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.
Int J Antimicrob Agents. 2017 05; 49(5):579-588.IJ

Abstract

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.

Authors+Show Affiliations

Zhongshan Hospital affiliated to Fudan University, Shanghai, China.Viet-Duc Hospital, Hanoi, Viet Nam.Korea University Anam Hospital, Seoul, Republic of Korea.Fuzhou General Hospital of Nanjing Military Region, Fuzhou, China.Gia Dinh People Hospital, Ho Chi Minh, Viet Nam.Affiliated Hospital of Guilin Medical University, Guangxi, China.Global Medicines Development, AstraZeneca, 199 Liangjing Road, Zhangjiang Hi-tech Park, Shanghai 201203, China. Electronic address: jie.song2@astrazeneca.com.Statistical Services Unit, University of Sheffield, Sheffield, UK.AstraZeneca, Waltham, MA, USA.AstraZeneca, Wilmington, DE, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

28363526

Citation

Qin, Xinyu, et al. "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." International Journal of Antimicrobial Agents, vol. 49, no. 5, 2017, pp. 579-588.
Qin X, Tran BG, Kim MJ, et al. 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. Int J Antimicrob Agents. 2017;49(5):579-588.
Qin, X., Tran, B. G., Kim, M. J., Wang, L., Nguyen, D. A., Chen, Q., Song, J., Laud, P. J., Stone, G. G., & Chow, J. W. (2017). 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. International Journal of Antimicrobial Agents, 49(5), 579-588. https://doi.org/10.1016/j.ijantimicag.2017.01.010
Qin X, et al. 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. Int J Antimicrob Agents. 2017;49(5):579-588. PubMed PMID: 28363526.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2017/03/29/ PY - 2016/08/23/received PY - 2016/12/22/revised PY - 2017/01/06/accepted PY - 2017/4/2/pubmed PY - 2018/1/18/medline PY - 2017/4/2/entrez KW - Asia KW - Ceftazidime/avibactam KW - Complicated intra-abdominal infection KW - Efficacy KW - Phase 3 KW - Safety SP - 579 EP - 588 JF - International journal of antimicrobial agents JO - Int J Antimicrob Agents VL - 49 IS - 5 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. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/28363526/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(17)30096-1 DB - PRIME DP - Unbound Medicine ER -