A Safety and Efficacy Study of Doripenem in Participants With Nosocomial Pneumonia, Complicated Intra-Abdominal Infections and Urinary Tract Infections

Phase 4

Completed

• Conditions: Intra-abdominal Infections; Infection; Cross Infection; Bacterial Infections; Pneumonia, Ventilator-Associated; Urinary Tract Infections
• Interventions: Drug: Doripenem

• Registration Number: NCT00965848
• Lead Sponsor: Janssen-Cilag Ltd.,Thailand

Brief Summary

The purpose of this study is to assess the safety and efficacy of doripenem in participants with nosocomial pneumonia (inflammation of the lungs in which the lungs become heavy; pneumonia occurring at least 48 hours after hospital admission), complicated intra-abdominal (in belly) infections and complicated urinary tract infections (bladder infections).

Detailed Description

This is an open-label (all people involved know the identity of the intervention), multi-center (conducted in more than 1 center) study, to evaluate the safety and effectiveness of doripenem in treating Thai participants with nosocomial pneumonia, complicated intra-abdominal and urinary tract infections. The study consists of 4 visits: Visit 1 (Baseline), Visit 2 (End-of-Treatment \[EOT\], up to Day 14), Visit 3 (Phone visit, Test-of-Cure \[TOC\], up to Day 14 after EOT) and Visit 4 (Phone visit, Day 90). Participants will receive 500 milligram (mg) of doripenem as intravenous infusion (directly into the vein) every 8 hours for at least 3 days after clinical response and extended up to 14 days. Efficacy will primarily be evaluated by determination of clinical response. Participants' safety will be monitored throughout the study.

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-08-24
• Study First Submitted QC: 2009-08-25
• Study First Posted: 2009-08-26
• Primary Completion: 2010-07
• Study Completion: 2010-07
• Results First Submitted: 2013-03-12
• Results First Submitted QC: 2013-07-25
• Results First Posted: 2013-08-28
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-27
• Last Update Posted: 2013-10-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

• Male or female participants with 18 years old age and above
• Diagnosed nosocomial pneumonia, complicated intra-abdominal infections and complicated urinary tract infections
• Must have evidence of a systemic inflammatory response syndrome with at least one of the these: fever (body temperature greater than 38 degree celcius) or hypothermia (body temperature less than 36 degree celcius) or elevated total peripheral white blood cell count greater than or equal to 12,000 cells per cubic millimeter or leukopenia with less than 4,000 cells per cubic millimeter or decrease in blood pressure relative to Baseline of greater than 15 millimeter of mercury systolic or increased pulse greater than 100 beats per minute (bpm) and respiratory rates greater than 20 bpm
• Candidate for treatment with carbapenems, with at least one of these conditions: Empirical therapy; suspected infection caused by carbapenem susceptible P. aeruginosa or carbapenem-susceptible A. baumannii or MDR gram negative bacteria or nosocomial infection with failure of previous treatment or modified therapy; known pathogens with resistance to cephalosporins,aminoglycosides, fluoroquinolones or beta-lactam/ batalactamase intibitor and susceptible to carbapenem or known infection caused by gram negative bacteria
• Signed informed consent

Exclusion Criteria

• Pregnant or lactating female participants
• History of severe allergies to antibiotics such as penicillins, cephalosporins and carbapenems
• Hypersensitivity to doripenem and/or excipients
• Previous use of carbapenems within 7 days of study entry
• Participants in terminal stage of malignancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nosocomial Pneumonia	Doripenem	Doripenem will be administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with nosocomial pneumonia up to maximum of 14 days.
Complicated Intra-Abdominal Infections	Doripenem	Doripenem will be administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated intra-abdominal infections up to maximum of 14 days.
Complicated Urinary Tract Infections	Doripenem	Doripenem will be administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated urinary tract infections up to maximum of 10 days.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs	Up to 30 days after last dose of study drug	An adverse event is any untoward medical occurrence in a participant administered with a pharmaceutical product. An adverse event does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The number of participants discontinued because of AEs were also reported.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Response at Test-of-Cure (TOC)	Up to Day 14 after End-of-Treatment (EOT)	Clinical response was defined as cure, improvement, failure and indeterminate. Cure=All signs/symptoms resolved/improved/lack of progression of all abnormalities; Improvement=Signs/symptoms of disease improved/resolved/ no modification in antibiotic therapy required and no worsening/appearance of new signs \& symptoms of disease; Failure=Persistence or worsening of signs/symptoms of disease or emergence of new signs/symptoms \& require any other antimicrobial therapy; \& Indeterminate=Insufficient data for treatment evaluation. The TOC visit (up to Day 14 after EOT) was conducted by phone. Participants who were assessed as cure or improvement at EOT will be evaluated for clinical response at TOC (up to Day 14 after EOT).
Percentage of Participants With Clinical Response at End-of-Treatment (EOT)	Up to Day 14 (EOT)	Clinical response was defined as cure, improvement, failure and indeterminate. Cure=All signs/symptoms resolved/improved/lack of progression of all abnormalities; Improvement=Signs/symptoms of disease improved/resolved/ no modification in antibiotic therapy required \& no worsening/appearance of new signs \& symptoms of disease; Failure=Persistence or worsening of signs/symptoms of disease or emergence of new signs/symptoms and require any other antimicrobial therapy; and Indeterminate=Insufficient data for treatment evaluation. 2 subjects were lost to follow-up.
Number of Participants With 90-day Mortality	up to Day 90	Number of Participants with 90-day mortality was defined as the number of participants who died by Day 90.