Trial Outcomes & Findings for Study Comparing Tigecycline Versus Ceftriaxone Sodium Plus Metronidazole in Complicated Intra-abdominal Infection (cIAI) (NCT NCT00230971)

Last Updated: 2013-02-25

Results Overview

CE population were those who completed TOC assessment of cure or failure (but not indeterminate) or, in case of premature discontinuation due to lack of efficacy, had completed end of treatment assessment such that assessment of clinical response could be made. Clinical response was assigned by investigator per protocol-specified guidelines and defined as: test article and initial intervention (operative and/or radiologically controlled drainage procedure) resolved the intra-abdominal infection. TOC performed 10-28 days after last dose of study drug.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

473 participants

Primary outcome timeframe

up to 6 weeks

Results posted on

2013-02-25

Participant Flow

Patients were recruited worldwide from November 2005 to July 2008.

Patients were screened according to the inclusion/exclusion criteria. Once informed consent was obtained, the patient was enrolled into the study and assigned a randomization number and a treatment regimen.

Participant milestones

Participant milestones
Measure	Tigecycline Tigecycline administered IV every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).	Ceftriaxone Ceftriaxone sodium 2 g administered IV once daily plus metronidazole 1 to 2 g daily in divided IV doses.
Randomization STARTED	235	238
Randomization COMPLETED	232	235
Randomization NOT COMPLETED	3	3
Baseline Participants STARTED	232	235
Baseline Participants COMPLETED	210	216
Baseline Participants NOT COMPLETED	22	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Tigecycline Tigecycline administered IV every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).	Ceftriaxone Ceftriaxone sodium 2 g administered IV once daily plus metronidazole 1 to 2 g daily in divided IV doses.
Randomization No study drug administered	3	3
Baseline Participants Lost to Follow-up	5	12
Baseline Participants Death	6	5
Baseline Participants Withdrawal by Subject	7	1
Baseline Participants Adverse Event	1	0
Baseline Participants No bacteria observed	1	0
Baseline Participants Failure to return	1	1
Baseline Participants Reintervention	1	0

Baseline Characteristics

Study Comparing Tigecycline Versus Ceftriaxone Sodium Plus Metronidazole in Complicated Intra-abdominal Infection (cIAI)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tigecycline n=232 Participants Tigecycline administered IV every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).	Ceftriaxone n=235 Participants Ceftriaxone sodium 2 g administered IV once daily plus metronidazole 1 to 2 g daily in divided IV doses.	Total n=467 Participants Total of all reporting groups
Age Continuous	48.55 years STANDARD_DEVIATION 18.37 • n=5 Participants	46.81 years STANDARD_DEVIATION 18.38 • n=7 Participants	47.67 years STANDARD_DEVIATION 18.37 • n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	72 Participants n=7 Participants	152 Participants n=5 Participants
Sex: Female, Male Male	152 Participants n=5 Participants	163 Participants n=7 Participants	315 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 6 weeks

Population: All patients who received at least 1 dose of study drug who had clinical evidence of a complicated intra-abdominal infection (cIAI) and completed the test-of-cure (TOC) assessment of cure or failure within 8 to 44 days after the last administration of study article. Patients with an indeterminate assessment were excluded.

Outcome measures

Outcome measures
Measure	Tigecycline n=198 Participants Tigecycline administered IV every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).	Ceftriaxone n=189 Participants Ceftriaxone sodium 2 g administered IV once daily plus metronidazole 1 to 2 g daily in divided IV doses.
Number of Clinically Evaluable (CE) Patients With Clinical Response of Cure at the Test-of-Cure (TOC) Visit	162 participants	150 participants

SECONDARY outcome

Timeframe: up to 6 weeks

Population: All patients who received ≥1 dose, had clinical evidence of complicated intra-abdominal infection, met all inclusion/exclusion criteria, completed TOC assessment within 8-44 days after last dose, and had a baseline culture with ≥1 identified isolate that was susceptible to both study drugs. Patients with an indeterminate assessment were excluded.

ME population were subjects who were clinically evaluable and had baseline culture with at least 1 identified isolate that was susceptible to study drug and comparator. The clinical response was assigned by the investigator according to the protocol-specified guidelines. A clinical response of cure was defined as: the test article and the initial intervention (operative and/or radiologically controlled drainage procedure) resolved the intra-abdominal infection.

Outcome measures

Outcome measures
Measure	Tigecycline n=119 Participants Tigecycline administered IV every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).	Ceftriaxone n=108 Participants Ceftriaxone sodium 2 g administered IV once daily plus metronidazole 1 to 2 g daily in divided IV doses.
Number of Microbiologically Evaluable (ME) Patients With a Clinical Response of Cure at Test-of-Cure (TOC) Visit	97 participants	86 participants

SECONDARY outcome

Timeframe: up to 6 weeks

Microbiological response was assessed at patient level was the combined responses for all baseline isolates identified in intra-abdominal and blood cultures. Eradication=baseline isolate not recovered from primary infection site/blood; Presumed Eradication=No sample for culture, clinical response was cure; Persistence=baseline isolate recovered from primary infection site/blood; Presumed Persistence=No sample available for culture, clinical response was failure; Superinfection=culture from primary infection site with new isolate not identified at baseline, clinical response was failure.

Outcome measures

Outcome measures
Measure	Tigecycline n=119 Participants Tigecycline administered IV every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).	Ceftriaxone n=108 Participants Ceftriaxone sodium 2 g administered IV once daily plus metronidazole 1 to 2 g daily in divided IV doses.
Number of Microbiologically Evaluable (ME) Patients by Microbiological Response at Test-of-Cure (TOC) Visit Eradication + Presumed Eradication	98 participants	86 participants
Number of Microbiologically Evaluable (ME) Patients by Microbiological Response at Test-of-Cure (TOC) Visit Persistence + Presumed Persistence	21 participants	22 participants
Number of Microbiologically Evaluable (ME) Patients by Microbiological Response at Test-of-Cure (TOC) Visit Superinfection	3 participants	0 participants

SECONDARY outcome

Timeframe: up to 6 weeks

Population: All patients who received at least 1 dose of study drug.

Healthcare resource utilization assessment included days of overall inpatient hospitalization, days of primary inpatient hospitalization, days of Intensive Care Unit (ICU) treatment and days of non-ICU inpatient hospitalization

Outcome measures

Outcome measures
Measure	Tigecycline n=232 Participants Tigecycline administered IV every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).	Ceftriaxone n=235 Participants Ceftriaxone sodium 2 g administered IV once daily plus metronidazole 1 to 2 g daily in divided IV doses.
Number of Days of Inpatient Healthcare Resource Utilization on or Before Test-of-Cure Inpatient hospitalization, non-ICU	11.09 days Standard Deviation 9.21	10.80 days Standard Deviation 7.93
Number of Days of Inpatient Healthcare Resource Utilization on or Before Test-of-Cure Overall inpatient hospitalization	13.03 days Standard Deviation 12.45	12.69 days Standard Deviation 10.25
Number of Days of Inpatient Healthcare Resource Utilization on or Before Test-of-Cure Primary inpatient hospitalization	12.62 days Standard Deviation 12.28	12.16 days Standard Deviation 9.75
Number of Days of Inpatient Healthcare Resource Utilization on or Before Test-of-Cure ICU treatment	8.24 days Standard Deviation 9.47	6.14 days Standard Deviation 8.70

Adverse Events

Tigecycline

Serious events: 37 serious events

Other events: 173 other events

Deaths: 0 deaths

Ceftriaxone

Serious events: 38 serious events

Other events: 155 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tigecycline n=232 participants at risk Tigecycline administered IV every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).	Ceftriaxone n=235 participants at risk Ceftriaxone sodium 2 g administered IV once daily plus metronidazole 1 to 2 g daily in divided IV doses.
Gastrointestinal disorders Nausea	21.1% 49/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	21.3% 50/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Vomiting	17.2% 40/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	13.2% 31/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Diarrhea	11.6% 27/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	7.2% 17/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Constipation	1.3% 3/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	3.4% 8/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Infection	7.8% 18/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	6.4% 15/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Metabolism and nutrition disorders Hypokalemia	3.4% 8/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	5.5% 13/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Metabolism and nutrition disorders Alkaline phosphatase increased	3.4% 8/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Nervous system disorders Insomina	1.7% 4/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	3.0% 7/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Blood and lymphatic system disorders Thrombocythemia	3.0% 7/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	2.6% 6/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Injury, poisoning and procedural complications Local reacation to procedure	3.9% 9/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	2.6% 6/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.

Additional Information

U. S. Contact Center

Wyeth

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Tigecycline n=232 participants at risk Tigecycline administered IV every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).	Ceftriaxone n=235 participants at risk Ceftriaxone sodium 2 g administered IV once daily plus metronidazole 1 to 2 g daily in divided IV doses.
General disorders Infection	3.0% 7/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	1.7% 4/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Sepsis	1.7% 4/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	2.1% 5/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Abscess	1.3% 3/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	1.3% 3/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Septic shock	1.7% 4/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Peritonitis	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Abdominal pain	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Fever	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Pain	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Scleroderma	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
General disorders Traumatic hematoma	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Gastrointestinal hemorrhage	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Intestinal perforation	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Colitis	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Diarrhea	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Duodenal ulcer hemorrhage	0.86% 2/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Vomiting	0.86% 2/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Blood in stool	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Cholelithiasis	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Gastrointestinal disorder	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Intestinal necrosis	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Jaundice	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Large intestine perforation	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Liver function tests abnormal	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Gastrointestinal disorders Nausea	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonia	2.6% 6/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	1.3% 3/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory distress syndrome	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Lung edema	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Metabolism and nutrition disorders Healing abnormal	2.6% 6/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	2.1% 5/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Metabolism and nutrition disorders Acidosis	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Metabolism and nutrition disorders Amylase increased	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Metabolism and nutrition disorders Dehydration	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Vascular disorders Pulmonary embolus	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	1.3% 3/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Vascular disorders Shock	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Cardiac disorders Atrial fibrillation	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Vascular disorders Cerebral ischemia	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Vascular disorders Cerebrovascular accident	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Vascular disorders Deep vein thrombosis	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Cardiac disorders Left heart failure	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Vascular disorders Peripheral vascular disease	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Cardiac disorders Ventricular fibrillation	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Renal and urinary disorders Acute kidney failure	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Renal and urinary disorders Kidney function abnormal	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Renal and urinary disorders Urolithiasis	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Injury, poisoning and procedural complications Local reaction to procedure	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.85% 2/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Blood and lymphatic system disorders Disseminated vascular coagulation	0.43% 1/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.00% 0/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.
Blood and lymphatic system disorders International normalized ratio increased	0.00% 0/232 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.	0.43% 1/235 Total # Affected patients includes duplicate patients that had more than one non-serious adverse events.