Study Evaluating Tigecycline Versus Ceftriaxone In Complicated Intra-Abdominal Infections & Community Acquired Pneumonia

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to compare the safety of tigecycline versus a ceftriaxone regimen in pediatric subjects (aged 8 to 17 years) with complicated intra-abdominal infections (cIAI) and community acquired pneumonia (CAP).

Official Title
-----------------
Multicenter, Randomized, And Double-Blind Study To Evaluate The Safety Of Tigecycline Versus A Ceftriaxone Regimen In The Treatment Of Complicated Intra-Abdominal Infections And Community-Acquired Pneumonia In Subjects Of 8-17 Years

Conditions
-----------------
Community Acquired Bacterial Pneumonia, Complicated Intra-Abdominal Infection

Intervention / Treatment
-----------------
* Drug: Tigecycline
* Drug: Tigecycline
* Drug: cIAI: Ceftriaxone with metronidazole, plus if applicable aminoglycoside
* Drug: CAP: Ceftriaxone, plus if applicable oral clarithromycin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects 8 to 17 years old. Children with bone maturation less than 8 years old should be enrolled with caution due to potential risk of tooth discoloration. Have a diagnosis of a serious infection (complicated intra-abdominal infections [cIAI] or community acquired pneumonia [CAP] as applicable) requiring hospitalization and administration of IV antibiotic therapy. Criteria related indication (cIAI or CAP - as applicable), e.g., sign of systemic infection, signs and symptom. Exclusion Criteria: Subject with any concomitant illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and/or completion of the study, or could preclude the evaluation of the subject's response (e.g., life expectancy <30 days).

Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A. Tigecycline<br> | Drug: Tigecycline<br>* Subject with cIAI: Dosing information for subjects 8 to 11 years old is currently under investigation and will be determined later. Subjects 12 to 17 years old will receive tigecycline 50 mg IV every 12 hours, metronidazole placebo IV will be administered every 8 hours. In addition, at the discretion of the investigator, an aminoglycoside placebo IV may also be administered.<br>* Other names: Tygacil;Drug: Tigecycline<br>* Subject with CAP: IV therapy period: Dosing information for subjects 8 to 11 years old is currently under investigation and will be determined later. Subjects 12 to 17 years old will receive tigecycline 50 mg IV every 12h. At the discretion of the investigator oral clarithromycin placebo may be given every 12h. Oral therapy period: If oral switch criteria are met, on or after Day 4 amoxicillin/clavulanate may be prescribed (40 mg/kg per day divided into 3 equal doses, maximum of 500 mg/dose to subjects weighing less than 40 kg and 500 mg every 8h to subjects weighing 40 kg or greater). In addition, if oral clarithromycin or placebo had been given during the IV period, oral clarithromycin may be given every 12h (7.5 mg/kg, maximum dose 500 mg for subjects 8 to 11 years old, 500 mg for subjects 12 to 17 years old).<br>* Other names: Tygacil;|
| Active Comparator: B. Ceftriaxone regimen<br> | Drug: cIAI: Ceftriaxone with metronidazole, plus if applicable aminoglycoside<br>* Subject with cIAI: Subjects will receive ceftriaxone 35 mg/kg (maximum of 1 g/dose) IV every 12 hours, metronidazole 10 mg/kg (maximum of 1 g/dose) IV will be administered every 8 hours. In addition, at the discretion of the investigator, an aminoglycoside IV (adjusted dose if necessary) may also be given.<br>Drug: CAP: Ceftriaxone, plus if applicable oral clarithromycin<br>* Subject with CAP: IV therapy period: Subjects will receive ceftriaxone 35 mg/kg (maximum of 1 g/dose) IV every 12h. At the discretion of the investigator, oral clarithromycin may be given every 12h (7.5 mg/kg, maximum dose 500 mg for subjects 8 to 11 years old, 500 mg for subjects 12 to 17 years old). Oral therapy period: If oral switch criteria are met, on or after Day 4 amoxicillin/clavulanate may be prescribed (40 mg/kg per day divided into 3 equal doses, maximum of 500 mg/dose to subjects weighing less than 40 kg and 500 mg every 8h to subjects weighing 40 kg or greater). In addition, if oral clarithromycin or placebo had been given during the IV period, oral clarithromycin may be given every 12h (7.5 mg/kg, maximum dose 500 mg for subjects 8 to 11 years old, 500 mg for subjects 12 to 17 years old).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy response (cure, failure, or indeterminate) at the test of cure (TOC) visit for 2 co-primary populations: the clinically evaluable (CE) and clinical modified Intent-to-Treat (c-mITT) populations |  | 2 to 7 weeks for cIAI and 2 to 5 weeks for CAP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response at the IV last day of therapy (LDOT) for co-primary populations: the CE and c-mITT populations |  | 5 days to 4 weeks for cIAI and 5 days to 2 weeks for CAP | 
| Clinical response at follow up (FUP) visits for co-primary populations: the CE and c-mITT populations |  | 5 to 9 weeks for cIAI and 5 to 7 weeks for CAP | 
| Microbiological response at the subject and the pathogen level |  | 5 to 9 weeks for cIAI and 5 to 7 weeks for CAP | 
| Response rate by pathogen and minimum inhibitory concentration (MIC) value |  | 5 to 9 weeks for cIAI and 5 to 7 weeks for CAP | 
| Response rates for polymicrobial/monomicrobial infections, and susceptibility evaluations |  | 5 to 9 weeks for cIAI and 5 to 7 weeks for CAP | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
children, pediatry, pneumonia, intra-abdominal, infection