Bacterial Pneumonia, Infections, Nosocomial, Pneumonia, Ventilator-Associated Pneumonia
Conditions
Keywords
Pneumonia, Lung Infection, Bacterial Infection, Hospital-Acquired Infection, Ventilator Infection, Antibiotic Therapy
Brief summary
The purpose of this study is to evaluate the effectiveness and safety of doripenem monohydrate in the treatment of patients with nosocomial (hospital-acquired) pneumonia.
Detailed description
Nosocomial pneumonia (NP) accounts for approximately 15% of all hospital-acquired infections. The incidence of NP rises in patients who are on breathing machines. The death rate for NP can be as high as 30%. NP caused by bacteria, such as Pseudomonas aeruginosa, has been associated with an increased death rate compared to other pathogens. Prompt use of appropriate antibiotics is essential. Compounding the issue of nosocomial infections is the increasing rate to which bacteria develop resistance to antibiotics. This hospital based trial is studying doripenem in patients who have nosocomial pneumonia to see if it is effective against bacteria associated with this serious bacterial infection. The duration of treatment can be anywhere from 8 to 14 days. Safety evaluations, such as vital signs and laboratory tests will be performed upon enrollment, after 4 days on therapy, after 9 days on therapy for those on greater than 8 days, at the end of therapy, 7 to 14 days after the end of therapy, and 28 to 35 days after the end of therapy. Adverse events will be collected throughout the study. Clinical response to doripenem therapy will be assessed 7 to 14 days after the end of therapy and the long-term clinical response to doripenem therapy will be assessed 28 to 35 days after the end of therapy. Doripenem IV will be administered for a duration of treatment from 8 to 14 days.
Interventions
DRUGdoripenem
1g i.v. infused over 4 hours every 8 hours for 8 to 14 days
Sponsors
PriCara, Unit of Ortho-McNeil, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients suffering from Nosocomial Pneumonia or Ventilator-Associated Pneumonia * All patients must be hospitalized throughout the treatment period * Patients must have microbiological samples (respiratory secretions) suitable for culture and microscopy
Exclusion criteria
* Known or suspected severe kidney impairment * Known or suspected liver dysfunction * Treatment with any investigational drug or device within 30 days before enrollment * Patients with one or more of the following: cystic fibrosis, lung abscess, active tuberculosis * Women who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response Rates and 95% Confidence Intervals at the Test-of-Cure Assessment. | 5 to 21 days after the last dose of study therapy, or at early termination. | The table below shows the percentage of subjects who had a clinical response of clinical cure at the Late Follow-up Visit as assigned by the medical monitor. A clinical response of clinical cure is defined as no further antibacterial therapy needed for treatment of the infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response Rates at the Late Follow-up Assessment. | 28 to 35 days after last dose of study therapy | The table below shows the percentage of subjects who had a clinical response of clinical cure at the Late Follow-up Visit as assigned by the medical monitor. A clinical response of clinical cure is defined as no further antibacterial therapy needed for treatment of the infection. |
Countries
Argentina, Canada, Chile, Croatia, France, India, Russia, Ukraine, United States
Participant flow
Pre-assignment details
Two enrolled subjects didn't take study medication and weren't qualified for safety population.
Participants by arm
| Arm | Count |
|---|---|
| Doripenem 1g i.v. infused over 4 hours every 8 hours from day 1 to day 8 to 14, depending on length of treatment | 183 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| End of Therapy to Test of Cure | Death | 3 |
| End of Therapy to Test of Cure | Lost to Follow-up | 2 |
| End of Therapy to Test of Cure | OTHER | 2 |
| End of Therapy to Test of Cure | Withdrawal by Subject | 1 |
| Treatment Period | Adverse Event | 7 |
| Treatment Period | Death | 14 |
| Treatment Period | OTHER | 30 |
| Treatment Period | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Doripenem |
|---|---|
| Age Continuous | 56 years STANDARD_DEVIATION 20.23 |
| BMI | 27.4 kg/m^2 STANDARD_DEVIATION 8.63 |
| ethnicity HISPANIC OR LATINO | 20 participants |
| ethnicity NOT HISPANIC OR LATINO | 158 participants |
| ethnicity OTHER | 5 participants |
| race AMERICAN INDIAN OR ALASKA | 2 participants |
| race ASIAN | 14 participants |
| race BLACK OR AFRICAN AMERICAN | 14 participants |
| race OTHER, SPECIFY | 2 participants |
| race WHITE | 151 participants |
| Region of Enrollment ARGENTINA | 4 participants |
| Region of Enrollment CANADA | 6 participants |
| Region of Enrollment CHILE | 9 participants |
| Region of Enrollment CROATIA | 21 participants |
| Region of Enrollment FRANCE | 6 participants |
| Region of Enrollment INDIA | 10 participants |
| Region of Enrollment RUSSIA | 2 participants |
| Region of Enrollment UKRAINE | 5 participants |
| Region of Enrollment USA | 120 participants |
| Sex: Female, Male Female | 71 Participants |
| Sex: Female, Male Male | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 93 / 183 |
| serious Total, serious adverse events | 70 / 183 |
Outcome results
Primary
Clinical Response Rates and 95% Confidence Intervals at the Test-of-Cure Assessment.
The table below shows the percentage of subjects who had a clinical response of clinical cure at the Late Follow-up Visit as assigned by the medical monitor. A clinical response of clinical cure is defined as no further antibacterial therapy needed for treatment of the infection.
Time frame: 5 to 21 days after the last dose of study therapy, or at early termination.
Population: Clinically Evaluable: Subset of the ITT population who received at least 5 days of study medication unless deemed a clinical failure with at least 2 full days of therapy, and excluding those subjects with a clinical outcome of Not Evaluable at the TOC assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Doripenem | Clinical Response Rates and 95% Confidence Intervals at the Test-of-Cure Assessment. | All Clinically Evaluable Subjects | 63.9 Percentage of participants |
| Doripenem | Clinical Response Rates and 95% Confidence Intervals at the Test-of-Cure Assessment. | Subjects with Nosocomial Pneumonia | 66.0 Percentage of participants |
| Doripenem | Clinical Response Rates and 95% Confidence Intervals at the Test-of-Cure Assessment. | Subjects with Ventilator Associated Pneumonia | 64.4 Percentage of participants |
| Doripenem | Clinical Response Rates and 95% Confidence Intervals at the Test-of-Cure Assessment. | Subjects with Healthcare Associated Pneumonia | 50.0 Percentage of participants |
Secondary
Clinical Response Rates at the Late Follow-up Assessment.
The table below shows the percentage of subjects who had a clinical response of clinical cure at the Late Follow-up Visit as assigned by the medical monitor. A clinical response of clinical cure is defined as no further antibacterial therapy needed for treatment of the infection.
Time frame: 28 to 35 days after last dose of study therapy
Population: Clinically Evaluable: Subset of the ITT population who received at least 5 days of study medication unless deemed a clinical failure with at least 2 full days of therapy, and excluding those subjects with a clinical outcome of Not Evaluable at the TOC assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Doripenem | Clinical Response Rates at the Late Follow-up Assessment. | All Clinically Evaluable Subjects | 83.3 Percentage of participants |
| Doripenem | Clinical Response Rates at the Late Follow-up Assessment. | Subjects with Nosocomial Pneumonia | 82.9 Percentage of participants |
| Doripenem | Clinical Response Rates at the Late Follow-up Assessment. | Subjects with Ventilator Associated Pneumonia | 84.2 Percentage of participants |
| Doripenem | Clinical Response Rates at the Late Follow-up Assessment. | Subjects with Healthcare Associated Pneumonia | 80.0 Percentage of participants |