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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01721408
• Collaborator: (none)
• Enrollment: 470
• Locations: 47
• Arms: 2
• Actual Duration (Months): 35
• Patients Per Site: 10
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Intra-abdominal Infection	Drug: Tigecycline; Drug: Imipenem/cilastatin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 470 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Clinical Response at the Test-of-Cure (TOC) Assessment Within the Clinically Evaluable (CE) Population [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)]

   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).

2. Clinical Response at the TOC Assessment Within the Modified Intent-to-Treat (mITT) Population [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)]

   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).

Secondary Outcome Measures

1. Clinical Response at the TOC Assessment Within the Microbiologically Evaluable (ME) Population [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)]

   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).

2. Microbiological Response at the Subject Level in the ME Population at the TOC Assessment [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)]

   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.

Other Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) by Relationship and Seriousness [From the first dose of study treatment through post therapy follow-up (28 days after the last dose of therapy)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anqing City Hospital	Anqing	Anhui	China	246003
2	Department of Hepatobiliary Surgery, Peking University People's Hospital	Xicheng District	Beijing	China	100044
3	Zhongshan Hospital Xiamen University	Xiamen	Fujian	China	361004
4	Zhangzhou Municipal Hospital of Fujian Province	Zhangzhou	Fujian	China	363000
5	Department of General Surgery, the First Affiliated Hospital Of Guangzhou Medical University	Guangzhou	Guangdong	China	510120
6	The First Affiliated Hospital of JiNan University/General Surgery	GuangZhou	Guangdong	China	510630
7	The First Hospital of Shantou University School of Medicine	Shantou	Guangdong	China	515041
8	Shenzhen Second People's Hosptial/Department of hepatobiliary surgery	Shenzhen	Guangdong	China	518039
9	Affiliated Hospital of Guilin Medical University	Guilin	Guangxi	China	541001
10	HaiKou Municipal People's Hospital	Haikou	Hainan	China	570208
11	Hainan Provincial People's Hospital	Haikou	Hainan	China	570311
12	The Third People's Hospital of Hainan Province/department of general surgery	Sanya	Hainan	China	572000
13	Tongji Medical College, Huazhong University of Science and Technology, The Central Hospital of Wuhan	Wuhan	Hubei	China	430014
14	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei	China	430030
15	Zhongnan Hospital of Wuhan University/Intensive Care Unit	Wuhan	Hubei	China	430071
16	Xiangya Hospital Central-South University/General Surgery	Changsha	Hunan	China	410008
17	The Third Xiangya Hospital of Central South University/Department of General Surgery	Changsha	Hunan	China	410013
18	The Third Hospital of Changsha/Department of Surgery	Changsha	Hunan	China	410015
19	Baotou Central Hospital	Baotou	Inner Mongolia	China	014000
20	The Affiliated Jiangyin Hospital of Southeast University Medical College, General Surgery Department	Jiangyin	Jiangsu	China	214400
21	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China	215004
22	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China	215006
23	Yangzhou No.1 People's Hospital	Yangzhou	Jiangsu	China	225001
24	Jilin Province People's Hospital	Changchun	Jilin	China	130021
25	The First Hospital of Jilin University/Surgery	Changchun	Jilin	China	130021
26	The Second Hospital of Jilin University	Changchun	Jilin	China	130041
27	Qinghai Provincial People's Hospital	Xining	Qinghai	China	810007
28	Binzhou Medical University Hospital	Bin Zhou	Shandong	China	256603
29	Shanghai Fengxian District Central Hospital, Department of Surgery	Shanghai	Shanghai	China	201400
30	Department of General Surgery, Sichuan Provincial People's Hospital	Chengdu	Sichuan	China	610072
31	General Hospital of Chengdu Military Region of PLA	Chengdu	Sichuan	China	610083
32	First people's Hospital of Kunming	Kunming	Yunnan	China	650011
33	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou	Zhejiang	China	310003
34	Taizhou Hospital of Zhejiang Province	Linhai	Zhejiang	China	317000
35	Lishui People's Hospital/Intensive Care Unit	Lishui	Zhejiang	China	323000
36	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang	China	325000
37	China Meitan General Hospital/General Surgery Department	Beijing		China	100028
38	Department of General Surgery,Beijing Shijitan Hospital,Capital Medical University	Beijing		China	100038
39	Navy General Hospital PLA China/Genaral Surgery Department	Beijing		China	100048
40	Peking University Third Hospital	Beijing		China	100191
41	Department of General Surgery, Peking Union Medical College Hospital	Beijing		China	100730
42	Institute of Antibiotics, Hua Shan Hospital, Fudan University	Shanghai		China	200040
43	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai		China	200092
44	Zhongshan Hospital Affiliated to Fudan University Qingpu Branch, Department of Surgery,	Shanghai		China	201700
45	Tianjin Union Medical Center	Tianjin		China	300000
46	Department of General Surgery, Tianjin Medical University General Hospital	Tianjin		China	300052
47	Tianjin Nankai Hospital	Tianjin		China	300100

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01721408
• Other Study ID Numbers: B1811185
• First Posted: Nov 4, 2012
• Last Update Posted: Apr 9, 2018
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Infections; Communicable Diseases; Intraabdominal Infections; Imipenem; Tigecycline; Cilastatin

Study Results

Participant Flow

Pre-assignment Detail	Of the total of 470 participants randomized, 235 were randomized to each treatment group. Seven participants (4 in tigecycline group and 3 in imipenem/cilastatin group) did not receive study treatment. One participant was randomized to imipenem/cilastatin group but received tigecycline and was reported and analyzed under the tigecycline group.

Arm/Group Title	Tigecycline 50mg	Imipenem/Cilastatin
Arm/Group Description	Participants were administered with tigecycline every 12 hours (an initial intravenous [IV] dose of 100 mg followed by 50 mg twice a day [BID] approximately every 12 hours) and placebo (100-mL of normal saline) IV doses every 12 hours beginning 6 hours after the initial IV dose of tigecycline.	Participants were administered with imipenem/cilastatin (approximately 100-mL IV infusion) intravenously approximately every 6 hours. IV placebo (100 mL of normal saline) was required to be dosed immediately After the first dose of imipenem/cilastatin.
Period Title: Overall Study
STARTED	232	231
COMPLETED	196	207
NOT COMPLETED	36	24

Baseline Characteristics

Arm/Group Title	Tigecycline 50mg	Imipenem/Cilastatin	Total
Arm/Group Description	Participants were administered with tigecycline every 12 hours (an initial intravenous [IV] dose of 100 mg followed by 50 mg twice a day [BID] approximately every 12 hours) and placebo (100-mL of normal saline) IV doses every 12 hours beginning 6 hours after the initial IV dose of tigecycline.	Participants were administered with imipenem/cilastatin (approximately 100-mL IV infusion) intravenously approximately every 6 hours. IV placebo (100 mL of normal saline) was required to be dosed immediately After the first dose of imipenem/cilastatin.	Total of all reporting groups
Overall Participants	232	231	463
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.4 (18.1)	48.2 (17.6)	48.3 (17.8)
Sex: Female, Male (Count of Participants)
Female	83 35.8%	81 35.1%	164 35.4%
Male	149 64.2%	150 64.9%	299 64.6%

Outcome Measures

1. Primary Outcome

Title	Clinical Response at the Test-of-Cure (TOC) Assessment Within the Clinically Evaluable (CE) Population
Description	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).
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The CE population was defined as all clinical modified intent-to-treat (c-mITT) participants who satisfied clinical evaluability criteria and had no major protocol violations.

Arm/Group Title	Tigecycline 50mg	Imipenem/Cilastatin
Arm/Group Description	Participants were administered with tigecycline every 12 hours (an initial intravenous [IV] dose of 100 mg followed by 50 mg twice a day [BID] approximately every 12 hours) and placebo (100-mL of normal saline) IV doses every 12 hours beginning 6 hours after the initial IV dose of tigecycline.	Participants were administered with imipenem/cilastatin (approximately 100-mL IV infusion) intravenously approximately every 6 hours. IV placebo (100 mL of normal saline) was required to be dosed immediately After the first dose of imipenem/cilastatin.
Measure Participants	207	205
Cure	89.9 38.8%	96.6 41.8%
Failure	10.1 4.4%	3.4 1.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tigecycline 50mg, Imipenem/Cilastatin
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assuming that the 2 treatments were equally effective, with cure rates of 75 % at the TOC assessment, the study was powered to ensure with 90% probability that the lower limit of a 2-sided 95% confidence interval (CI) for the true difference (tigecycline minus imipenem/cilastatin) in cure rates was greater than -15%.
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	See method of CI
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-6.7
	Confidence Interval	(2-Sided) 95%; -12.0 to -1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Used the asymptotic method corrected for continuity with normal distribution approximation. Non-inferiority test was conducted on the CE population. If non-inferiority was concluded, superiority test was conducted on both the CE and mITT populations.

2. Secondary Outcome

Title	Clinical Response at the TOC Assessment Within the Microbiologically Evaluable (ME) Population
Description	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).
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The ME population was defined as all CE participants who satisfied the pre-specified ME evaluable criteria.

Arm/Group Title	Tigecycline 50mg	Imipenem/Cilastatin
Arm/Group Description	Participants were administered with tigecycline every 12 hours (an initial intravenous [IV] dose of 100 mg followed by 50 mg twice a day [BID] approximately every 12 hours) and placebo (100-mL of normal saline) IV doses every 12 hours beginning 6 hours after the initial IV dose of tigecycline.	Participants were administered with imipenem/cilastatin (approximately 100-mL IV infusion) intravenously approximately every 6 hours. IV placebo (100 mL of normal saline) was required to be dosed immediately After the first dose of imipenem/cilastatin.
Measure Participants	125	107
Cure	88.0 37.9%	95.3 41.3%
Failure	12.0 5.2%	4.7 2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tigecycline 50mg, Imipenem/Cilastatin
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was concluded if the lower limit of the 2-sided CI for the difference in cure rates between treatment groups (tigecycline minus imipenem/cilastatin) was greater than -15%.
Statistical Test of Hypothesis	p-Value	0.0277
	Comments
	Method	See method of CI
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-7.3
	Confidence Interval	(2-Sided) 95%; -15.2 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	CIs and p-values for between-group treatment difference in cure rate were calculated by the asymptotic method corrected for continuity with normal distribution approximation.

3. Secondary Outcome

Title	Microbiological Response at the Subject Level in the ME Population at the TOC Assessment
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The ME population was defined as all CE participants who satisfied the pre-specified ME evaluable criteria. n=number of participants with each microbiological response.

Arm/Group Title	Tigecycline 50mg	Imipenem/Cilastatin
Arm/Group Description	Participants were administered with tigecycline every 12 hours (an initial intravenous [IV] dose of 100 mg followed by 50 mg twice a day [BID] approximately every 12 hours) and placebo (100-mL of normal saline) IV doses every 12 hours beginning 6 hours after the initial IV dose of tigecycline.	Participants were administered with imipenem/cilastatin (approximately 100-mL IV infusion) intravenously approximately every 6 hours. IV placebo (100 mL of normal saline) was required to be dosed immediately After the first dose of imipenem/cilastatin.
Measure Participants	125	107
Eradication (N=125, 107)	88.0 37.9%	95.3 41.3%
Documented Eradication (N=110, 102)	2.7 1.2%	0.0 0%
Presumed Eradication (N=110, 102)	97.3 41.9%	100.0 43.3%
Persistence (N=125, 107)	10.4 4.5%	4.7 2%
Documented Persistence (N=13, 5)	7.7 3.3%	20.0 8.7%
Presumed Persistence (N=13, 5)	92.3 39.8%	80.0 34.6%
Superinfection (N=125, 107)	1.6 0.7%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tigecycline 50mg, Imipenem/Cilastatin
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was concluded if the lower limit of the 2-sided CI for the difference in eradication rates between treatment groups (tigecycline minus imipenem/cilastatin) was greater than -15%.
Statistical Test of Hypothesis	p-Value	0.0277
	Comments
	Method	See method of CI
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-7.3
	Confidence Interval	(2-Sided) 95%; -15.2 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	CIs and p-values for between-group treatment difference in eradication rates were calculated by the asymptotic method corrected for continuity with normal distribution approximation.

4. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) by Relationship and Seriousness
Description	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.
Time Frame	From the first dose of study treatment through post therapy follow-up (28 days after the last dose of therapy)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of investigational product. There was 1 participant (who was included in the safety population) had 7 AEs including 1 SAE which were identified after database release and were not reflected in the table.

Arm/Group Title	Tigecycline 50mg	Imipenem/Cilastatin
Arm/Group Description	Participants were administered with tigecycline every 12 hours (an initial intravenous [IV] dose of 100 mg followed by 50 mg twice a day [BID] approximately every 12 hours) and placebo (100-mL of normal saline) IV doses every 12 hours beginning 6 hours after the initial IV dose of tigecycline.	Participants were administered with imipenem/cilastatin (approximately 100-mL IV infusion) intravenously approximately every 6 hours. IV placebo (100 mL of normal saline) was required to be dosed immediately After the first dose of imipenem/cilastatin.
Measure Participants	232	231
Number (#) of Participants with AEs	131 56.5%	108 46.8%
# of Participants with Treatment-Related AEs	53 22.8%	29 12.6%
# of Participants with SAEs	32 13.8%	15 6.5%
# of Participants with Treatment-Related SAEs	19 8.2%	7 3%

5. Primary Outcome

Title	Clinical Response at the TOC Assessment Within the Modified Intent-to-Treat (mITT) Population
Description	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).
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The MITT population was defined as all randomized participants who received at least 1 dose of investigational product.

Arm/Group Title	Tigecycline 50mg	Imipenem/Cilastatin
Arm/Group Description	Participants were administered with tigecycline every 12 hours (an initial intravenous [IV] dose of 100 mg followed by 50 mg twice a day [BID] approximately every 12 hours) and placebo (100-mL of normal saline) IV doses every 12 hours beginning 6 hours after the initial IV dose of tigecycline.	Participants were administered with imipenem/cilastatin (approximately 100-mL IV infusion) intravenously approximately every 6 hours. IV placebo (100 mL of normal saline) was required to be dosed immediately After the first dose of imipenem/cilastatin.
Measure Participants	232	231
Cure	82.8 35.7%	88.7 38.4%
Failure	10.3 4.4%	3.5 1.5%
Indeterminate	6.9 3%	7.8 3.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tigecycline 50mg, Imipenem/Cilastatin
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was concluded if the lower limit of the 2-sided CI for the difference in cure rates between treatment groups (tigecycline minus imipenem/cilastatin) was greater than -15%.
Statistical Test of Hypothesis	p-Value	0.0040
	Comments
	Method	See method of CI
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) 95%; -12.8 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Used the asymptotic method corrected for continuity with normal distribution approximation. Non-inferiority test was conducted on the CE population. If non-inferiority was concluded, superiority test was conducted on both the CE and mITT populations.

Adverse Events

Time Frame	From the first dose of study treatment (for non-serious AEs)/the time that the subject provided informed consent (for SAEs) through post therapy follow-up (28 days after the last dose of therapy)
Arm/Group Title	Tigecycline 50mg		Imipenem/Cilastatin
Arm/Group Description	Participants were administered with tigecycline every 12 hours (an initial intravenous [IV] dose of 100 mg followed by 50 mg twice a day [BID] approximately every 12 hours) and placebo (100-mL of normal saline) IV doses every 12 hours beginning 6 hours after the initial IV dose of tigecycline.		Participants were administered with imipenem/cilastatin (approximately 100-mL IV infusion) intravenously approximately every 6 hours. IV placebo (100 mL of normal saline) was required to be dosed immediately After the first dose of imipenem/cilastatin.
All Cause Mortality
	Tigecycline 50mg		Imipenem/Cilastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tigecycline 50mg		Imipenem/Cilastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/232 (13.8%)		16/232 (6.9%)
Cardiac disorders
Atrial fibrillation	1/232 (0.4%)		0/232 (0%)
Gastrointestinal disorders
Abdominal pain	0/232 (0%)		1/232 (0.4%)
Pancreatitis acute	1/232 (0.4%)		0/232 (0%)
General disorders
Drug ineffective	21/232 (9.1%)		9/232 (3.9%)
Sudden death	1/232 (0.4%)		0/232 (0%)
Hepatobiliary disorders
Bile duct stone	0/232 (0%)		1/232 (0.4%)
Cholecystitis acute	1/232 (0.4%)		0/232 (0%)
Hepatic failure	1/232 (0.4%)		0/232 (0%)
Jaundice cholestatic	0/232 (0%)		1/232 (0.4%)
Infections and infestations
Abdominal infection	1/232 (0.4%)		0/232 (0%)
Lung infection	3/232 (1.3%)		0/232 (0%)
Postoperative wound infection	7/232 (3%)		2/232 (0.9%)
Injury, poisoning and procedural complications
Postoperative fever	1/232 (0.4%)		0/232 (0%)
Investigations
Amylase increased	0/232 (0%)		1/232 (0.4%)
Psychiatric disorders
Delirium	0/232 (0%)		1/232 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/232 (0%)		1/232 (0.4%)
Other (Not Including Serious) Adverse Events
	Tigecycline 50mg		Imipenem/Cilastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/232 (24.6%)		34/232 (14.7%)
Gastrointestinal disorders
Nausea	24/232 (10.3%)		10/232 (4.3%)
Vomiting	19/232 (8.2%)		10/232 (4.3%)
General disorders
Pyrexia	18/232 (7.8%)		20/232 (8.6%)
Infections and infestations
Postoperative wound infection	14/232 (6%)		1/232 (0.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.