Bacterial Infections, Cross Infection, Infection, Intra-abdominal Infections, Pneumonia, Ventilator-Associated, Urinary Tract Infections
Conditions
Keywords
Pneumonia, Ventilator-Associated, Intra-abdominal Infections, Urinary tract Infections, Doripenem, Doribax
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.
Interventions
DRUGDoripenem
Doripenem 500 mg will be administered as 1 or 4 hours intravenous infusion, after every 8 hours up to maximum of 14 days.
Sponsors
Janssen-Cilag Ltd.,Thailand
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligibility Criteria: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
| 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. |
Countries
Thailand
Participant flow
Pre-assignment details
The total number of participants enrolled were 270, out of which 268 participants had adequate information for analysis.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population | 264 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 11 | 1 | 5 |
| Overall Study | Indeterminate Clinical Outcome | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Not Clinically Evaluable | 7 | 1 | 1 |
| Overall Study | Other | 5 | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 64.6 Years STANDARD_DEVIATION 16.5 |
| Sex: Female, Male Female | 118 Participants |
| Sex: Female, Male Male | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 66 / 107 | 22 / 34 | 56 / 127 |
| serious Total, serious adverse events | 45 / 107 | 14 / 34 | 31 / 127 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs
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.
Time frame: Up to 30 days after last dose of study drug
Population: Intent-to-treat population (ITT) included all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nosocomial Pneumonia | Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs | Participants with AEs | 66 Participants |
| Nosocomial Pneumonia | Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs | Participants discontinued because of AEs | 0 Participants |
| Complicated Intra-Abdominal Infections | Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs | Participants with AEs | 22 Participants |
| Complicated Intra-Abdominal Infections | Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs | Participants discontinued because of AEs | 0 Participants |
| Complicated Urinary Tract Infections | Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs | Participants with AEs | 56 Participants |
| Complicated Urinary Tract Infections | Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs | Participants discontinued because of AEs | 2 Participants |
Secondary
Number of Participants With 90-day Mortality
Number of Participants with 90-day mortality was defined as the number of participants who died by Day 90.
Time frame: up to Day 90
Population: The cMITT included all participants who received any dose of study medication and met the clinical definition in the protocol. N signifies those participants who were evaluated for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nosocomial Pneumonia | Number of Participants With 90-day Mortality | 42 Participants |
| Complicated Intra-Abdominal Infections | Number of Participants With 90-day Mortality | 16 Participants |
| Complicated Urinary Tract Infections | Number of Participants With 90-day Mortality | 22 Participants |
Secondary
Percentage of Participants With Clinical Response at 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 & 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.
Time frame: Up to Day 14 (EOT)
Population: Clinical Modified-Intent-to-Treat (cMITT) included all participants who received any dose of study medication. N signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Indeterminate | 18.6 Percentage of participants |
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Cure | 38.1 Percentage of participants |
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Improvement | 30.9 Percentage of participants |
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Failure | 11.3 Percentage of participants |
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Other: Lost to Follow-Up | 1.0 Percentage of participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Improvement | 33.3 Percentage of participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Other: Lost to Follow-Up | 0.0 Percentage of participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Failure | 6.1 Percentage of participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Indeterminate | 3.0 Percentage of participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Cure | 57.6 Percentage of participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Cure | 71.2 Percentage of participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Improvement | 20.8 Percentage of participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Indeterminate | 5.6 Percentage of participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Other: Lost to Follow-Up | 0.8 Percentage of participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at End-of-Treatment (EOT) | Failure | 1.6 Percentage of participants |
Secondary
Percentage of Participants With Clinical Response at Test-of-Cure (TOC)
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).
Time frame: Up to Day 14 after End-of-Treatment (EOT)
Population: The cMITT included all participants who received any dose of study medication. N signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Cure | 56.96 Percentage of Participants |
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Improvement | 0.00 Percentage of Participants |
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Failure | 5.06 Percentage of Participants |
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Indeterminate | 15.19 Percentage of Participants |
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Other: Lost to Follow-Up | 1.27 Percentage of Participants |
| Nosocomial Pneumonia | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Not evaluable | 21.52 Percentage of Participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Not evaluable | 11.11 Percentage of Participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Cure | 66.67 Percentage of Participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Indeterminate | 14.81 Percentage of Participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Other: Lost to Follow-Up | 0.00 Percentage of Participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Improvement | 0.00 Percentage of Participants |
| Complicated Intra-Abdominal Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Failure | 7.41 Percentage of Participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Improvement | 0.00 Percentage of Participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Failure | 6.25 Percentage of Participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Not evaluable | 3.13 Percentage of Participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Indeterminate | 5.21 Percentage of Participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Cure | 85.42 Percentage of Participants |
| Complicated Urinary Tract Infections | Percentage of Participants With Clinical Response at Test-of-Cure (TOC) | Other: Lost to Follow-Up | 0.00 Percentage of Participants |