Study Comparing Tigecycline Versus Ceftriaxone Sodium Plus Metronidazole in Complicated Intra-abdominal Infection - Study Results

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Single Group Assignment
Conditions:	Appendicitis Cholecystitis Cross Infection Diverticulitis Peritonitis
Interventions:	Drug: tigecycline Drug: ceftriaxone sodium + metronidazole

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were recruited worldwide from September 2005 to February 2008.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects were screened up to two days.

Reporting Groups

	Description
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.

Participant Flow: Overall Study

	Tigecycline	Ceftriaxone Sodium + Metronidazole
STARTED	236	231
COMPLETED	215	215
NOT COMPLETED	21	16
Lost to Follow-up	9	9
Withdrawal by Subject	6	3
Protocol Deviation	3	2
Death	3	1
Lack of Efficacy	0	1

Baseline Characteristics

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Reporting Groups

	Description
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.

Baseline Measures

	Tigecycline	Ceftriaxone Sodium + Metronidazole	Total
Number of Participants [units: participants]	236	231	467
Age [units: years] Mean ± Standard Deviation	48.17 ± 18.05	48.79 ± 17.46	48.48 ± 17.74
Gender [units: participants]
Female	93	72	165
Male	143	159	302
Region of Enrollment [units: participants]
United States	163	169	332
Mexico	1	0	1
Canada	39	25	64
Argentina	4	2	6
Brazil	23	23	46
Chile	6	12	18

Outcome Measures

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1. Primary:

Number of Clinically Evaluable Patients With Clinical Response of Cure at Test-of-Cure (TOC) Visit. [ 10-21 days after the last dose of test article ]

Measure Type	Primary
Measure Title	Number of Clinically Evaluable Patients With Clinical Response of Cure at Test-of-Cure (TOC) Visit.
Measure Description	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.
Time Frame	10-21 days after the last dose of test article
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.

Measured Values

	Tigecycline	Ceftriaxone Sodium + Metronidazole
Number of Participants Analyzed [units: participants]	189	187
Number of Clinically Evaluable Patients With Clinical Response of Cure at Test-of-Cure (TOC) Visit. [units: participants]	133	139

Statistical Analysis 1 for Number of Clinically Evaluable Patients With Clinical Response of Cure at Test-of-Cure (TOC) Visit.

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	0.009
Risk Difference (RD) ^[4]	-4.0
95% Confidence Interval	( -13.1 to 5.1 )

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2. Secondary:

Number of Microbiologically Evaluable Patients With a Clinical Response of Cure at Test-of-Cure (TOC) Visit. [ 10-21 days after the last dose of test article ]

Measure Type	Secondary
Measure Title	Number of Microbiologically Evaluable Patients With a Clinical Response of Cure at Test-of-Cure (TOC) Visit.
Measure Description	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.
Time Frame	10-21 days after the last dose of test article
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.

Measured Values

	Tigecycline	Ceftriaxone Sodium + Metronidazole
Number of Participants Analyzed [units: participants]	138	137
Number of Microbiologically Evaluable Patients With a Clinical Response of Cure at Test-of-Cure (TOC) Visit. [units: participants]	91	96

Statistical Analysis 1 for Number of Microbiologically Evaluable Patients With a Clinical Response of Cure at Test-of-Cure (TOC) Visit.

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	0.020
Risk Difference (RD) ^[4]	-3.4
95% Confidence Interval	( -14.5 to 7.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
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[2]	Other relevant information, such as adjustments or degrees of freedom:
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[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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3. Secondary:

Number of Patients by Microbiologic Response at Test-of-Cure (TOC) Visit. [ 10-21 days after the last dose of test article ]

Measure Type	Secondary
Measure Title	Number of Patients by Microbiologic Response at Test-of-Cure (TOC) Visit.
Measure Description	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.
Time Frame	10-21 days after the last dose of test article
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.

Measured Values

	Tigecycline	Ceftriaxone Sodium + Metronidazole
Number of Participants Analyzed [units: participants]	138	137
Number of Patients by Microbiologic Response at Test-of-Cure (TOC) Visit. [units: participants]
Eradication and presumed eradication	94	98
Persistence and presumed persistence	44	39
Superinfection	7	3

Statistical Analysis 1 for Number of Patients by Microbiologic Response at Test-of-Cure (TOC) Visit.

Groups ^[1]	All groups
Method ^[2]	Method of Mehrotra and Railkar
P Value ^[3]	0.015
Risk Difference (RD) ^[4]	-2.9
95% Confidence Interval	( -13.9 to 8.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
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[2]	Other relevant information, such as adjustments or degrees of freedom:
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[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4]	Other relevant estimation information:
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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: U. S. Contact Center
Organization: Wyeth
e-mail: clintrialresults@wyeth.com

No publications provided

Responsible Party:	Wyeth ( Wyeth (Registry Contact: Clinical Trial Registry Specialist) )
Study ID Numbers:	3074A1-400
Study First Received:	September 12, 2005
Results First Received:	February 27, 2009
Last Updated:	November 19, 2009
ClinicalTrials.gov Identifier:	NCT00195351 History of Changes
Health Authority:	Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica; Brazil: National Committee of Ethics in Research; Canada: Health Canada; Chile: Instituto de Salud Publica de Chile; Mexico: National Council of Science and Technology; United States: Institutional Review Board