Trial Outcomes & Findings for A Study To Determine The Efficacy And Safety Of Tigecycline Compared With Imipenem/Cliastatin to Treat Complicated Intra-Abdominal Infection (NCT NCT01721408)

Last Updated: 2018-04-09

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

470 participants

Primary outcome timeframe

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)

Results posted on

2018-04-09

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Tigecycline 50mg 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.	Imipenem/Cilastatin 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.
Overall Study STARTED	232	231
Overall Study COMPLETED	196	207
Overall Study NOT COMPLETED	36	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Tigecycline 50mg 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.	Imipenem/Cilastatin 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.
Overall Study Adverse Event	6	1
Overall Study Death	1	0
Overall Study Insufficient clinical response	15	6
Overall Study No longer willing to participate study	9	10
Overall Study Protocol Violation	0	2
Overall Study Other	3	3
Overall Study Lost to Follow-up	1	2
Overall Study Does not meet entrance criteria	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tigecycline 50mg n=232 Participants 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.	Imipenem/Cilastatin n=231 Participants 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 n=463 Participants Total of all reporting groups
Age, Continuous	48.4 years STANDARD_DEVIATION 18.1 • n=5 Participants	48.2 years STANDARD_DEVIATION 17.6 • n=7 Participants	48.3 years STANDARD_DEVIATION 17.8 • n=5 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	81 Participants n=7 Participants	164 Participants n=5 Participants
Sex: Female, Male Male	149 Participants n=5 Participants	150 Participants n=7 Participants	299 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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)

Population: 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.

Outcome measures

Outcome measures
Measure	Tigecycline 50mg n=207 Participants 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.	Imipenem/Cilastatin n=205 Participants 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.
Clinical Response at the Test-of-Cure (TOC) Assessment Within the Clinically Evaluable (CE) Population Cure	89.9 percentage of participants Interval 84.9 to 93.6	96.6 percentage of participants Interval 93.1 to 98.6
Clinical Response at the Test-of-Cure (TOC) Assessment Within the Clinically Evaluable (CE) Population Failure	10.1 percentage of participants Interval 6.4 to 15.1	3.4 percentage of participants Interval 1.4 to 6.9

PRIMARY outcome

Timeframe: 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)

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

Outcome measures

Outcome measures
Measure	Tigecycline 50mg n=232 Participants 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.	Imipenem/Cilastatin n=231 Participants 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.
Clinical Response at the TOC Assessment Within the Modified Intent-to-Treat (mITT) Population Cure	82.8 percentage of participants Interval 77.3 to 87.4	88.7 percentage of participants Interval 83.9 to 92.5
Clinical Response at the TOC Assessment Within the Modified Intent-to-Treat (mITT) Population Failure	10.3 percentage of participants Interval 6.7 to 15.0	3.5 percentage of participants Interval 1.5 to 6.7
Clinical Response at the TOC Assessment Within the Modified Intent-to-Treat (mITT) Population Indeterminate	6.9 percentage of participants Interval 4.0 to 11.0	7.8 percentage of participants Interval 4.7 to 12.0

SECONDARY outcome

Timeframe: 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)

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

Outcome measures

Outcome measures
Measure	Tigecycline 50mg n=125 Participants 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.	Imipenem/Cilastatin n=107 Participants 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.
Clinical Response at the TOC Assessment Within the Microbiologically Evaluable (ME) Population Cure	88.0 percentage of participants Interval 81.0 to 93.1	95.3 percentage of participants Interval 89.4 to 98.5
Clinical Response at the TOC Assessment Within the Microbiologically Evaluable (ME) Population Failure	12.0 percentage of participants Interval 6.9 to 19.0	4.7 percentage of participants Interval 1.5 to 10.6

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Tigecycline 50mg n=125 Participants 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.	Imipenem/Cilastatin n=107 Participants 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.
Microbiological Response at the Subject Level in the ME Population at the TOC Assessment Presumed Persistence (N=13, 5)	92.3 percentage of participants Interval 64.0 to 99.8	80.0 percentage of participants Interval 28.4 to 99.5
Microbiological Response at the Subject Level in the ME Population at the TOC Assessment Eradication (N=125, 107)	88.0 percentage of participants Interval 81.0 to 93.1	95.3 percentage of participants Interval 89.4 to 98.5
Microbiological Response at the Subject Level in the ME Population at the TOC Assessment Documented Eradication (N=110, 102)	2.7 percentage of participants Interval 0.6 to 7.8	0.0 percentage of participants Interval 0.0 to 3.6
Microbiological Response at the Subject Level in the ME Population at the TOC Assessment Presumed Eradication (N=110, 102)	97.3 percentage of participants Interval 92.2 to 99.4	100.0 percentage of participants Interval 96.4 to 100.0
Microbiological Response at the Subject Level in the ME Population at the TOC Assessment Persistence (N=125, 107)	10.4 percentage of participants Interval 5.7 to 17.1	4.7 percentage of participants Interval 1.5 to 10.6
Microbiological Response at the Subject Level in the ME Population at the TOC Assessment Documented Persistence (N=13, 5)	7.7 percentage of participants Interval 0.2 to 36.0	20.0 percentage of participants Interval 0.5 to 71.6
Microbiological Response at the Subject Level in the ME Population at the TOC Assessment Superinfection (N=125, 107)	1.6 percentage of participants Interval 0.2 to 5.7	0.0 percentage of participants Interval 0.0 to 3.4

OTHER_PRE_SPECIFIED outcome

Timeframe: From the first dose of study treatment through post therapy follow-up (28 days after the last dose of therapy)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Tigecycline 50mg n=232 Participants 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.	Imipenem/Cilastatin n=231 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Relationship and Seriousness Number (#) of Participants with AEs	131 participants	108 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Relationship and Seriousness # of Participants with SAEs	32 participants	15 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Relationship and Seriousness # of Participants with Treatment-Related AEs	53 participants	29 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Relationship and Seriousness # of Participants with Treatment-Related SAEs	19 participants	7 participants

Adverse Events

Tigecycline 50mg

Serious events: 32 serious events

Other events: 57 other events

Deaths: 0 deaths

Imipenem/Cilastatin

Serious events: 16 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tigecycline 50mg n=232 participants at risk 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.	Imipenem/Cilastatin n=232 participants at risk 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.
Gastrointestinal disorders Nausea	10.3% 24/232 • 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)	4.3% 10/232 • 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)
Gastrointestinal disorders Vomiting	8.2% 19/232 • 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)	4.3% 10/232 • 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)
General disorders Pyrexia	7.8% 18/232 • 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)	8.6% 20/232 • 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)
Infections and infestations Postoperative wound infection	6.0% 14/232 • 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)	0.43% 1/232 • 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)

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Tigecycline 50mg n=232 participants at risk 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.	Imipenem/Cilastatin n=232 participants at risk 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.
Cardiac disorders Atrial fibrillation	0.43% 1/232 • 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)	0.00% 0/232 • 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)
Gastrointestinal disorders Abdominal pain	0.00% 0/232 • 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)	0.43% 1/232 • 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)
Gastrointestinal disorders Pancreatitis acute	0.43% 1/232 • 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)	0.00% 0/232 • 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)
General disorders Drug ineffective	9.1% 21/232 • 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)	3.9% 9/232 • 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)
General disorders Sudden death	0.43% 1/232 • 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)	0.00% 0/232 • 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)
Hepatobiliary disorders Bile duct stone	0.00% 0/232 • 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)	0.43% 1/232 • 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)
Hepatobiliary disorders Cholecystitis acute	0.43% 1/232 • 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)	0.00% 0/232 • 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)
Hepatobiliary disorders Hepatic failure	0.43% 1/232 • 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)	0.00% 0/232 • 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)
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/232 • 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)	0.43% 1/232 • 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)
Infections and infestations Abdominal infection	0.43% 1/232 • 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)	0.00% 0/232 • 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)
Infections and infestations Lung infection	1.3% 3/232 • 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)	0.00% 0/232 • 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)
Infections and infestations Postoperative wound infection	3.0% 7/232 • 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)	0.86% 2/232 • 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)
Injury, poisoning and procedural complications Postoperative fever	0.43% 1/232 • 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)	0.00% 0/232 • 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)
Investigations Amylase increased	0.00% 0/232 • 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)	0.43% 1/232 • 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)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/232 • 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)	0.43% 1/232 • 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)
Psychiatric disorders Delirium	0.00% 0/232 • 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)	0.43% 1/232 • 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)