Trial Outcomes & Findings for Study Comparing Tigecycline Versus Ceftriaxone Sodium Plus Metronidazole in Complicated Intra-abdominal Infection (NCT NCT00195351)
NCT ID: NCT00195351
Last Updated: 2013-02-25
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
467 participants
Primary outcome timeframe
10-21 days after the last dose of test article
Results posted on
2013-02-25
Participant Flow
Subjects were recruited worldwide from September 2005 to February 2008.
Subjects were screened up to two days.
Participant milestones
| Measure |
Tigecycline
Administered intravenously every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).
|
Ceftriaxone Sodium + Metronidazole
Ceftriaxone sodium 2 g administered intravenously once daily plus metronidazole 1 g to 2 g daily in divided IV doses.
|
|---|---|---|
|
Overall Study
STARTED
|
236
|
231
|
|
Overall Study
COMPLETED
|
215
|
215
|
|
Overall Study
NOT COMPLETED
|
21
|
16
|
Reasons for withdrawal
| Measure |
Tigecycline
Administered intravenously every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).
|
Ceftriaxone Sodium + Metronidazole
Ceftriaxone sodium 2 g administered intravenously once daily plus metronidazole 1 g to 2 g daily in divided IV doses.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
9
|
9
|
|
Overall Study
Withdrawal by Subject
|
6
|
3
|
|
Overall Study
Protocol Deviation
|
3
|
2
|
|
Overall Study
Death
|
3
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
Baseline Characteristics
Study Comparing Tigecycline Versus Ceftriaxone Sodium Plus Metronidazole in Complicated Intra-abdominal Infection
Baseline characteristics by cohort
| Measure |
Tigecycline
n=236 Participants
Administered intravenously every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).
|
Ceftriaxone Sodium + Metronidazole
n=231 Participants
Ceftriaxone sodium 2 g administered intravenously once daily plus metronidazole 1 g to 2 g daily in divided IV doses.
|
Total
n=467 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
48.17 years
STANDARD_DEVIATION 18.05 • n=93 Participants
|
48.79 years
STANDARD_DEVIATION 17.46 • n=4 Participants
|
48.48 years
STANDARD_DEVIATION 17.74 • n=27 Participants
|
|
Sex: Female, Male
Female
|
93 Participants
n=93 Participants
|
72 Participants
n=4 Participants
|
165 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
143 Participants
n=93 Participants
|
159 Participants
n=4 Participants
|
302 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
163 participants
n=93 Participants
|
169 participants
n=4 Participants
|
332 participants
n=27 Participants
|
|
Region of Enrollment
Mexico
|
1 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Region of Enrollment
Canada
|
39 participants
n=93 Participants
|
25 participants
n=4 Participants
|
64 participants
n=27 Participants
|
|
Region of Enrollment
Argentina
|
4 participants
n=93 Participants
|
2 participants
n=4 Participants
|
6 participants
n=27 Participants
|
|
Region of Enrollment
Brazil
|
23 participants
n=93 Participants
|
23 participants
n=4 Participants
|
46 participants
n=27 Participants
|
|
Region of Enrollment
Chile
|
6 participants
n=93 Participants
|
12 participants
n=4 Participants
|
18 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 10-21 days after the last dose of test articlePopulation: All patients who received ≥1 dose of study drug, who had clinical evidence of complicated intra-abdominal infection, met all inclusion and exclusion criteria, and completed TOC assessment within 8-44 days after last dose of study drug. Patients with an indeterminate assessment were excluded.
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
| Measure |
Tigecycline
n=189 Participants
Administered intravenously every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).
|
Ceftriaxone Sodium + Metronidazole
n=187 Participants
Ceftriaxone sodium 2 g administered intravenously once daily plus metronidazole 1 g to 2 g daily in divided IV doses.
|
|---|---|---|
|
Number of Clinically Evaluable Patients With Clinical Response of Cure at Test-of-Cure (TOC) Visit.
|
133 participants
|
139 participants
|
SECONDARY outcome
Timeframe: 10-21 days after the last dose of test articlePopulation: 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.
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
| Measure |
Tigecycline
n=138 Participants
Administered intravenously every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).
|
Ceftriaxone Sodium + Metronidazole
n=137 Participants
Ceftriaxone sodium 2 g administered intravenously once daily plus metronidazole 1 g to 2 g daily in divided IV doses.
|
|---|---|---|
|
Number of Microbiologically Evaluable Patients With a Clinical Response of Cure at Test-of-Cure (TOC) Visit.
|
91 participants
|
96 participants
|
SECONDARY outcome
Timeframe: 10-21 days after the last dose of test articlePopulation: 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 baseline culture with ≥1 identified isolate that was susceptible to both study drugs. Patients with an indeterminate assessment were excluded.
Microbiologic response assessed at patient level was combined microbiologic responses for all baseline isolates identified in intra-abdominal/blood cultures. Eradication=baseline isolate not recovered from primary infection site/blood; Presumed Eradication=no material available for culture but response was cure; Persistence=baseline isolate recovered from primary infection site/blood; Presumed Persistence=no material available for culture but response was failure; Superinfection=culture from primary infection site was positive for new isolate not identified at baseline \& response was failure.
Outcome measures
| Measure |
Tigecycline
n=138 Participants
Administered intravenously every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).
|
Ceftriaxone Sodium + Metronidazole
n=137 Participants
Ceftriaxone sodium 2 g administered intravenously once daily plus metronidazole 1 g to 2 g daily in divided IV doses.
|
|---|---|---|
|
Number of Patients by Microbiologic Response at Test-of-Cure (TOC) Visit.
Eradication and presumed eradication
|
94 participants
|
98 participants
|
|
Number of Patients by Microbiologic Response at Test-of-Cure (TOC) Visit.
Persistence and presumed persistence
|
44 participants
|
39 participants
|
|
Number of Patients by Microbiologic Response at Test-of-Cure (TOC) Visit.
Superinfection
|
7 participants
|
3 participants
|
Adverse Events
Tigecycline
Serious events: 51 serious events
Other events: 195 other events
Deaths: 0 deaths
Ceftriaxone Sodium + Metronidazole
Serious events: 49 serious events
Other events: 189 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tigecycline
Administered intravenously every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).
|
Ceftriaxone Sodium + Metronidazole
Ceftriaxone sodium 2 g administered intravenously once daily plus metronidazole 1 g to 2 g daily in divided IV doses.
|
|---|---|---|
|
General disorders
Abscess
|
7.6%
18/236
|
5.6%
13/231
|
|
General disorders
Infection
|
1.3%
3/236
|
1.7%
4/231
|
|
General disorders
Abdominal pain
|
1.3%
3/236
|
1.3%
3/231
|
|
General disorders
Lymphocele
|
0.00%
0/236
|
1.7%
4/231
|
|
General disorders
Peritonitis
|
0.42%
1/236
|
0.87%
2/231
|
|
General disorders
Sepsis
|
0.00%
0/236
|
1.3%
3/231
|
|
General disorders
Chest pain
|
0.42%
1/236
|
0.43%
1/231
|
|
General disorders
Septic shock
|
0.85%
2/236
|
0.00%
0/231
|
|
General disorders
Hemoperitoneum
|
0.00%
0/236
|
0.43%
1/231
|
|
General disorders
Mesenteric fibrosis
|
0.42%
1/236
|
0.00%
0/231
|
|
General disorders
Retroperitoneal hemorrhage
|
0.00%
0/236
|
0.43%
1/231
|
|
General disorders
Traumatic hematoma
|
0.42%
1/236
|
0.00%
0/231
|
|
Gastrointestinal disorders
Ileus
|
1.3%
3/236
|
1.3%
3/231
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.85%
2/236
|
1.3%
3/231
|
|
Gastrointestinal disorders
Gastrointestinal carcinoma
|
0.85%
2/236
|
0.43%
1/231
|
|
Gastrointestinal disorders
Cholestatic jaundice
|
0.85%
2/236
|
0.00%
0/231
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/236
|
0.43%
1/231
|
|
Gastrointestinal disorders
Diarrhea
|
0.42%
1/236
|
0.00%
0/231
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/236
|
0.43%
1/231
|
|
Gastrointestinal disorders
Gastrointestinal hemorrhage
|
0.42%
1/236
|
0.00%
0/231
|
|
Gastrointestinal disorders
Hematemesis
|
0.00%
0/236
|
0.43%
1/231
|
|
Gastrointestinal disorders
Intestinal necrosis
|
0.42%
1/236
|
0.00%
0/231
|
|
Gastrointestinal disorders
Melena
|
0.00%
0/236
|
0.43%
1/231
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.85%
2/236
|
2.2%
5/231
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.42%
1/236
|
1.3%
3/231
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonia
|
0.42%
1/236
|
0.43%
1/231
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress syndrome
|
0.00%
0/236
|
0.87%
2/231
|
|
Respiratory, thoracic and mediastinal disorders
Carcinoma of the lung
|
0.42%
1/236
|
0.00%
0/231
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/236
|
0.43%
1/231
|
|
Cardiac disorders
Pulmonary embolus
|
1.3%
3/236
|
0.43%
1/231
|
|
Cardiac disorders
Atrial fibrillation
|
0.85%
2/236
|
0.00%
0/231
|
|
Vascular disorders
Deep vein thrombosis
|
0.85%
2/236
|
0.00%
0/231
|
|
Cardiac disorders
Hypotension
|
0.42%
1/236
|
0.43%
1/231
|
|
Cardiac disorders
Myocardial infarct
|
0.00%
0/236
|
0.87%
2/231
|
|
Vascular disorders
Cerebral ischemia
|
0.42%
1/236
|
0.00%
0/231
|
|
Vascular disorders
Cerebrovascular accident
|
0.42%
1/236
|
0.00%
0/231
|
|
Cardiac disorders
Congestive heart failure
|
0.00%
0/236
|
0.43%
1/231
|
|
Cardiac disorders
Coronary artery disorder
|
0.00%
0/236
|
0.43%
1/231
|
|
Cardiac disorders
Heart arrest
|
0.42%
1/236
|
0.00%
0/231
|
|
Vascular disorders
Hemorrhage
|
0.42%
1/236
|
0.00%
0/231
|
|
Vascular disorders
Mesenteric venous occousion
|
0.42%
1/236
|
0.00%
0/231
|
|
Metabolism and nutrition disorders
Healing abdominal
|
1.3%
3/236
|
0.43%
1/231
|
|
Metabolism and nutrition disorders
Acidosis
|
0.00%
0/236
|
0.43%
1/231
|
|
Metabolism and nutrition disorders
Blood urea nitrogen increased
|
0.00%
0/236
|
0.43%
1/231
|
|
Blood and lymphatic system disorders
Thrombocythemia
|
0.85%
2/236
|
0.00%
0/231
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/236
|
0.43%
1/231
|
|
Blood and lymphatic system disorders
International normalized ratio increased
|
0.42%
1/236
|
0.00%
0/231
|
|
Renal and urinary disorders
Acute kidney failure
|
0.00%
0/236
|
0.43%
1/231
|
|
Renal and urinary disorders
Pyelonephritis
|
0.42%
1/236
|
0.00%
0/231
|
|
Renal and urinary disorders
Urinary retention
|
0.42%
1/236
|
0.00%
0/231
|
|
General disorders
Trauma
|
0.00%
0/236
|
0.43%
1/231
|
Other adverse events
| Measure |
Tigecycline
Administered intravenously every 12 hours (an initial dose of 100 mg followed by 50 mg every 12 hours).
|
Ceftriaxone Sodium + Metronidazole
Ceftriaxone sodium 2 g administered intravenously once daily plus metronidazole 1 g to 2 g daily in divided IV doses.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
38.6%
91/236
|
27.7%
64/231
|
|
Gastrointestinal disorders
Vomiting
|
23.3%
55/236
|
17.7%
41/231
|
|
Gastrointestinal disorders
Diarrhea
|
17.8%
42/236
|
17.3%
40/231
|
|
Gastrointestinal disorders
Constipation
|
5.9%
14/236
|
6.1%
14/231
|
|
Gastrointestinal disorders
Ileus
|
3.4%
8/236
|
6.9%
16/231
|
|
Gastrointestinal disorders
Abdominal distension
|
2.1%
5/236
|
4.8%
11/231
|
|
Gastrointestinal disorders
Dyspepsia
|
3.8%
9/236
|
1.7%
4/231
|
|
Gastrointestinal disorders
Oral moniliasis
|
3.4%
8/236
|
0.43%
1/231
|
|
General disorders
Abdominal pain
|
9.3%
22/236
|
6.9%
16/231
|
|
General disorders
Abscess
|
9.7%
23/236
|
6.5%
15/231
|
|
General disorders
Headache
|
5.9%
14/236
|
9.5%
22/231
|
|
General disorders
Fever
|
7.2%
17/236
|
7.8%
18/231
|
|
General disorders
Infection
|
7.2%
17/236
|
3.9%
9/231
|
|
General disorders
Generalized edema
|
0.42%
1/236
|
3.0%
7/231
|
|
Metabolism and nutrition disorders
Hypokalemia
|
6.8%
16/236
|
9.1%
21/231
|
|
Metabolism and nutrition disorders
Healing abdominal
|
3.8%
9/236
|
3.5%
8/231
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
3.8%
9/236
|
3.5%
8/231
|
|
Metabolism and nutrition disorders
Peripheral edema
|
3.8%
9/236
|
3.0%
7/231
|
|
Metabolism and nutrition disorders
Hypoproteinemia
|
4.7%
11/236
|
1.7%
4/231
|
|
Metabolism and nutrition disorders
Amylase increased
|
3.4%
8/236
|
1.7%
4/231
|
|
Metabolism and nutrition disorders
Hypophophatemia
|
1.3%
3/236
|
3.9%
9/231
|
|
Metabolism and nutrition disorders
SGPT increased
|
3.0%
7/236
|
2.2%
5/231
|
|
Nervous system disorders
Insomina
|
9.7%
23/236
|
10.4%
24/231
|
|
Nervous system disorders
Anxiety
|
3.0%
7/236
|
5.2%
12/231
|
|
Nervous system disorders
Confusion
|
3.4%
8/236
|
0.87%
2/231
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
3.8%
9/236
|
3.5%
8/231
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.5%
6/236
|
4.3%
10/231
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary physical findings
|
3.0%
7/236
|
2.6%
6/231
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.1%
5/236
|
3.0%
7/231
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.7%
4/236
|
3.0%
7/231
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/236
|
3.0%
7/231
|
|
Blood and lymphatic system disorders
Thrombocythemia
|
5.5%
13/236
|
6.5%
15/231
|
|
Blood and lymphatic system disorders
Anemia
|
6.8%
16/236
|
3.5%
8/231
|
|
Blood and lymphatic system disorders
Leukocytosis
|
8.1%
19/236
|
1.7%
4/231
|
|
Cardiac disorders
Hypertension
|
3.8%
9/236
|
4.8%
11/231
|
|
Vascular disorders
Deep vein thrombosis
|
3.4%
8/236
|
0.43%
1/231
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.5%
13/236
|
5.2%
12/231
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.7%
4/236
|
3.0%
7/231
|
|
Surgical and medical procedures
Local reaction to procedure
|
7.6%
18/236
|
6.1%
14/231
|
|
General disorders
Taste perversion
|
0.85%
2/236
|
3.9%
9/231
|
Additional Information
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