A multicenter, double-blind, randomized, comparison study of the efficacy and safety of tigecycline to imipenem/cilastatin to treat complicated intra-abdominal infections in hospitalized subjects in China
Authors Chen Y, Zhu D, Zhang Y, Zhao Y, Chen G, Li P, Xu L, Yan P, Hickman MA, Xu X, Tawadrous M, Wible M
Received 20 April 2018
Accepted for publication 22 September 2018
Published 30 November 2018 Volume 2018:14 Pages 2327—2339
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 3
Editor who approved publication: Professor Deyun Wang
Yijian Chen,1,2,* Demei Zhu,1,2,* Yingyuan Zhang,1,2 Yongjie Zhao,3 Gang Chen,4 Ping Li,5 Lihong Xu,6 Ping Yan,6 M Anne Hickman,7 Xiajun Xu,6 Margaret Tawadrous,7 Michele Wible7
1Institute of Antibiotics, Huashan Hospital Fudan University, Shanghai, China; 2Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China; 3Department of General Surgery, Tianjin Union Medical Center, Tianjin, China; 4Department of Hepatobiliary Surgery, First People’s Hospital of Kunming, Kunming, China; 5Department of General Surgery, Sichuan Provincial People’s Hospital, Chengdu, China; 6Pfizer (China) Research & Development Co, Ltd, Shanghai, China; 7Pfizer Inc., Collegeville, PA, USA
*These authors contributed equally to this work
Purpose: To assess the efficacy and safety of tigecycline in treating complicated intra-abdominal infections (cIAIs) in hospitalized patients in China.
Patients and methods: A Phase IV, multicenter, randomized, double-blinded, active-controlled, non-inferiority study was conducted. Hospitalized cIAI patients ≥18 years of age were randomized (1:1) to receive intravenous tigecycline (initial dose 100 mg, then 50 mg q12h) or imipenem/cilastatin (500 mg/500 mg or adjusted for renal dysfunction, q6h) for 5–14 days. The primary end point was clinical response for clinically evaluable (CE) subjects at test-of-cure (TOC) assessment.
Results: Four hundred and seventy subjects were randomized; 232 in the tigecycline and 231 in the imipenem/cilastatin group were treated. Tigecycline was non-inferior to imipenem/cilastatin with respect to clinical response at TOC for all CE subjects, ie, the lower bound of the two-sided 95% CI (−12.0%, −1.4%) for the treatment difference in cure rate, tigecycline (89.9%) minus imipenem/cilastatin (96.6%), was >−15%. As non-inferiority was concluded in the CE population, superiority of tigecycline over imipenem/cilastatin and superiority of imipenem/cilastatin over tigecycline were tested on the CE and the modified intent-to-treat (mITT) populations according to pre-specified statistical criteria, and neither could be demonstrated (the cure rate was 82.8% vs 88.7%, difference -6.0% [−12.8%, 0.8%], for the mITT population). The subject-level microbiological response rate at TOC for the microbiologically evaluable population was 88.0% (110/125) vs 95.3% (102/107, difference -7.3% [−15.2%, 0.5%]). Nausea, drug ineffectiveness, postoperative wound infection, vomiting, and pyrexia were the most common adverse events in tigecycline-treated subjects; pyrexia, nausea, vomiting, and increased alanine aminotransferase and aspartate aminotransferase levels were most common in imipenem/cilastatin-treated subjects; none were unanticipated.
Conclusion: Tigecycline was non-inferior to imipenem/cilastatin in treating hospitalized adult patients with cIAI. Superiority of tigecycline over imipenem/cilastatin or imipenem/cilastatin over tigecycline could not be demonstrated. Safety was consistent with the known profile for tigecycline.
ClinicalTrials.gov identifier: NCT01721408.
Keywords: tigecycline, imipenem/cilastatin, complicated intra-abdominal infections, non-inferiority
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