A Study To Determine The Efficacy And Safety Of Tigecycline Compared With Imipenem/Cliastatin to Treat Complicated Intra-Abdominal Infection

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.

This is a comparative study of the efficacy and safety of tigecycline to imipenem/cilastatin in hospitalized patients with a complicated intra-abdominal infection.

Study Overview

• Status: Completed
• Conditions: Intra-abdominal Infection
• Intervention / Treatment: Drug: Tigecycline; Drug: Imipenem/cilastatin

• Study Type: Interventional
• Enrollment (Actual): 470
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100028
    • China Meitan General Hospital/General Surgery Department
  • Beijing, China, 100038
    • Department of General Surgery,Beijing Shijitan Hospital,Capital Medical University
  • Beijing, China, 100048
    • Navy General Hospital PLA China/Genaral Surgery Department
  • Beijing, China, 100730
    • Department of General Surgery, Peking Union Medical College Hospital
  • Shanghai, China, 200040
    • Institute of Antibiotics, Hua Shan Hospital, Fudan University
  • Shanghai, China, 200092
    • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Shanghai, China, 201700
    • Zhongshan Hospital Affiliated to Fudan University Qingpu Branch, Department of Surgery,
  • Tianjin, China, 300000
    • Tianjin Union Medical Center
  • Tianjin, China, 300052
    • Department of General Surgery, Tianjin Medical University General Hospital
  • Tianjin, China, 300100
    • Tianjin Nankai Hospital
  • Anhui
    • Anqing, Anhui, China, 246003
      • Anqing City Hospital
  • Beijing
    • Xicheng District, Beijing, China, 100044
      • Department of Hepatobiliary Surgery, Peking University People's Hospital
  • Fujian
    • Xiamen, Fujian, China, 361004
      • Zhongshan Hospital Xiamen University
    • Zhangzhou, Fujian, China, 363000
      • Zhangzhou Municipal Hospital of Fujian Province
  • Guangdong
    • GuangZhou, Guangdong, China, 510630
      • The First Affiliated Hospital of JiNan University/General Surgery
    • Guangzhou, Guangdong, China, 510120
      • Department of General Surgery, the First Affiliated Hospital Of Guangzhou Medical University
    • Shantou, Guangdong, China, 515041
      • The First Hospital of Shantou University School of Medicine
    • Shenzhen, Guangdong, China, 518039
      • Shenzhen Second People's Hosptial/Department of hepatobiliary surgery
  • Guangxi
    • Guilin, Guangxi, China, 541001
      • Affiliated Hospital of Guilin Medical University
  • Hainan
    • Haikou, Hainan, China, 570208
      • HaiKou Municipal People's Hospital
    • Haikou, Hainan, China, 570311
      • Hainan Provincial People's Hospital
    • Sanya, Hainan, China, 572000
      • The Third People's Hospital of Hainan Province/department of general surgery
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430014
      • Tongji Medical College, Huazhong University of Science and Technology, The Central Hospital of Wuhan
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University/Intensive Care Unit
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central-South University/General Surgery
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University/Department of General Surgery
    • Changsha, Hunan, China, 410015
      • The Third Hospital of Changsha/Department of Surgery
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014000
      • Baotou Central Hospital
  • Jiangsu
    • Jiangyin, Jiangsu, China, 214400
      • The Affiliated Jiangyin Hospital of Southeast University Medical College, General Surgery Department
    • Suzhou, Jiangsu, China, 215004
      • The Second Affiliated Hospital of Soochow University
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital Of Soochow University
    • Yangzhou, Jiangsu, China, 225001
      • Yangzhou No.1 People's Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Province People's Hospital
    • Changchun, Jilin, China, 130041
      • The Second Hospital of Jilin University
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University/Surgery
  • Qinghai
    • Xining, Qinghai, China, 810007
      • Qinghai Provincial People's Hospital
  • Shandong
    • Bin Zhou, Shandong, China, 256603
      • Binzhou Medical University Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 201400
      • Shanghai Fengxian District Central Hospital, Department of Surgery
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Department of General Surgery, Sichuan Provincial People's Hospital
    • Chengdu, Sichuan, China, 610083
      • General Hospital of Chengdu Military Region of PLA
  • Yunnan
    • Kunming, Yunnan, China, 650011
      • First people's Hospital of Kunming
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of College of Medicine, Zhejiang University
    • Linhai, Zhejiang, China, 317000
      • Taizhou Hospital of Zhejiang Province
    • Lishui, Zhejiang, China, 323000
      • Lishui People's Hospital/Intensive Care Unit
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hospitalized male or female subjects, at least 18 year of age.
• Complicated intra-abdominal infection is present at most under two weeks duration.
• Minimal clinical criteria at the time of intra-abdominal infection diagnosis or highly suspected intra-abdominal infection.

Exclusion Criteria:

• Anticipated length of antibiotic therapy less than 5 days or the likelihood that the subject will not complete the course of treatment.
• Intra-abdominal infection known to be caused by 1 or more bacterial pathogens not susceptible to both of the study drugs.
• Had accepted non-study antibiotics more than 24 hr within 72 hrs before enrollment except for subjects declared prior failures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Drug: Tigecycline; every 12 hours (an initial intravenous dose of 100 mg followed by 50 mg twice a day approximately every 12 hours) and placebo intravenous doses every 12 hours beginning 6 hours after the initial intravenous dose of tigecycline for at least for 5 days and up to 14 days.
Active Comparator: Group B	Drug: Imipenem/cilastatin; every 6 hours intravenously, and the imipenem/cilastatin will be dosed by 500mg/500mg for the subjects with creatinine clearance equal or above 71ml/min/1.73m2 or dose will be adjusted by Schedule of Study Drug Administration for Subjects with Renal Impairment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response at the Test-of-Cure (TOC) Assessment Within the Clinically Evaluable (CE) Population	The clinical response was to be determined by the investigator and was classified as 1 of the following: cure (relevant clinical signs and symptoms of infection at baseline disappeared or recovered to normal and relevant non microbiological results of laboratory tests returned to normal level or the resolution of signs and symptoms so that at no further therapy was required), failure (participant required additional surgical or radiologic intervention and/or received additional anti-infection therapy to cure the infection since administration of study drug until TOC; or death after study Day 2 due to the infection or a treatment related AE or discontinuation due to a treatment related AE or received greater than 120% of the prescribed number of investigational product doses), or indeterminate (lost to follow-up; or died within 2 days after the first dose of study drug for any reason; or died after study Day 2 but prior to the TOC assessment because of non infection related reasons).	Day 3, Day 14 or last day of therapy (treatment duration was at least 5 days and up to 14 days), and TOC (14-21 days after the last dose of therapy)
Clinical Response at the TOC Assessment Within the Modified Intent-to-Treat (mITT) Population	The clinical response was to be determined by the investigator and was classified as 1 of the following: cure (relevant clinical signs and symptoms of infection at baseline disappeared or recovered to normal and relevant non microbiological results of laboratory tests returned to normal level or the resolution of signs and symptoms so that at no further therapy was required), failure (participant required additional surgical or radiologic intervention and/or received additional anti-infection therapy to cure the infection since administration of study drug until TOC; or death after study Day 2 due to the infection or a treatment related AE or discontinuation due to a treatment related AE or received greater than 120% of the prescribed number of investigational product doses), or indeterminate (lost to follow-up; or died within 2 days after the first dose of study drug for any reason; or died after study Day 2 but prior to the TOC assessment because of non infection related reasons).	Day 3, Day 14 or last day of therapy (treatment duration was at least 5 days and up to 14 days), and TOC (14-21 days after the last dose of therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response at the TOC Assessment Within the Microbiologically Evaluable (ME) Population	The clinical response was to be determined by the investigator and was classified as 1 of the following: cure (relevant clinical signs and symptoms of infection at baseline disappeared or recovered to normal and relevant non microbiological results of laboratory tests returned to normal level or the resolution of signs and symptoms so that at no further therapy was required), failure (participant required additional surgical or radiologic intervention and/or received additional anti-infection therapy to cure the infection since administration of study drug until TOC; or death after study Day 2 due to the infection or a treatment related AE or discontinuation due to a treatment related AE or received greater than 120% of the prescribed number of investigational product doses), or indeterminate (lost to follow-up; or died within 2 days after the first dose of study drug for any reason; or died after study Day 2 but prior to the TOC assessment because of non infection related reasons).	Day 3, Day 14 or last day of therapy (treatment duration was at least 5 days and up to 14 days), and TOC (14-21 days after the last dose of therapy)
Microbiological Response at the Subject Level in the ME Population at the TOC Assessment	The microbiological response at the subject level was described according to the following definitions of efficacy. Eradication (documented or presumed): none of the baseline pathogens were present in repeat intra-abdominal cultures from the original site of infection taken during the study or a clinical response of cure precluded the necessity of a repeat intra-abdominal culture. Persistence (documented or presumed): documented: any baseline intra-abdominal pathogen was present in the cultures obtained from the original site of the intra-abdominal abscess, peritonitis, or surgical wound infection during the study; Presumed: repeat microbiological data were not obtained for a participant with a clinical response of failure. Superinfection: Emergence of a new pathogen during therapy, at the site of infection with emergence or worsening of clinical signs and symptoms of infection.	Day 3, Day 14 or last day of therapy (treatment duration was at least 5 days and up to 14 days), and TOC (14-21 days after the last dose of therapy)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Relationship and Seriousness	An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both AEs and Non-SAEs.	From the first dose of study treatment through post therapy follow-up (28 days after the last dose of therapy)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Chen Y, Zhu D, Zhang Y, Zhao Y, Chen G, Li P, Xu L, Yan P, Hickman MA, Xu X, Tawadrous M, Wible M. 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. Ther Clin Risk Manag. 2018 Nov 30;14:2327-2339. doi: 10.2147/TCRM.S171821. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: October 31, 2012
• First Submitted That Met QC Criteria: November 1, 2012
• First Posted (Estimate): November 4, 2012

Study Record Updates

• Last Update Posted (Actual): April 9, 2018
• Last Update Submitted That Met QC Criteria: September 14, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Intraabdominal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protease Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Imipenem; Cilastatin; Tigecycline
• Other Study ID Numbers: B1811185