Ventilator Associated Pneumonia
Conditions
Brief summary
The purpose of this study is to see if the amount of antibiotics given for ventilator-associated pneumonia (VAP) can be decreased in order to reduce the risk of adverse effects associated with antibiotics, while at the same time ensuring the participant's safety.
Interventions
DRUGStandard of Care Antibiotic Therapy
Antibiotics will be administered as per the standard of care orally via tablet
Sponsors
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Surgical patient 2. Early VAP, defined as VAP occurring within 2 - 7 days of intubation (via endotracheal or tracheostomy tube) (9). VAP will be defined according to local institutional protocol. 3. Hospital length of stay (LOS) \< 10 days at the time of VAP diagnosis. 4. Patients are willing to provide informed consent or their Legally Authorized Representative (LAR) is willing to provide informed consent on their behalf when the patient is unable (i.e., cognitively impaired from sedation on a ventilator)
Exclusion criteria
1. Age \< 18 years 2. Prior episode of VAP for the index admission 3. VAP caused by any of the following pathogens: * Methicillin-resistant Staphylococcus aureus (MRSA) * Vancomycin-intermediate Staphylococcus aureus (VISA) * Pseudomonas aeruginosa * Vancomycin-resistant Enterococcus (VRE) * Acinetobacter baumanii * Stenotrophomonas maltophilia * Carbapenem-resistant Enterobacteriaceae (CRE) * Extended-spectrum beta lactamase-producing gram-negative bacilli 4. Causative pathogen not sensitive to choice of initial empiric antibiotic 5. Antibiotic therapy for \> 5 of the last 10 days preceding VAP diagnosis 6. Septic shock, defined as evidence of tissue hypoperfusion after adequate volume expansion, due to infection, and requiring \> 1 vasopressor (17) 7. Current or recent (within 30 days) use of immunosuppressive medications 8. LOS \> 72 hours at a transferring facility 9. Pregnancy or lactation 10. Legal arrest or incarceration 11. Moribund state in which death is imminent 12. ECMO (Extracorporeal membrane oxygenation) 13. Extubation prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Reoccurring VAP | Up to 21 days | VAP recurrence will be reported as the number of participants with VAP occurring following completion of initial therapy. |
| Antibiotic Free Days | Up to 30 days | The number of days where participant did not require the use of antibiotics |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement as Measured by the Change in Clinical Pulmonary Infection Score (CPIS) From the First Study Day to the Last | From baseline to the last study day, up to 30 days | Clinical improvement will be measured comparing the difference from the first study day to the last study day using daily Clinical Pulmonary Infection Score (CPIS) clinical score while enrolled in the study. CPIS has a total score ranging from 0 to 12 where a score of less than 6 indicates that the lung infection is considered controlled. A negative change may suggest improvement while a positive difference may suggest a worsening. |
| Number of Participants With VAP Relapse | Up to 30 days | VAP relapse will be reported as any recurrence of VAP caused by initial pathogen. |
| Ventilator-free Days | Up to 30 days | The average number of days participants did not use a ventilator |
| The Number of Participants With Empyema | Up to 30 days | The number of participants with empyema |
| Number of Days of Antibiotic Exposure | Up to 30 days | The number of days when the participant received antibiotics |
| The Number of Participants With Non-pulmonary Infections | Up to 30 days | The number of participants with Non-pulmonary infections |
| ICU-free Days | Up to 30 days | The average number of days participants were not in the ICU |
| Hospital Length Of Stay | Up to 1 year | Number of days participant was admitted in the hospital |
| In-hospital Mortality | Up to 1 year | The number of participants that died while admitted in the hospital will be reported |
| The Number of Participants That Received a Tracheostomy | Up to 30 days | The number of participants that received a tracheostomy |
| Amount of Antibiotic Exposure | Up to 30 days | Antibiotic exposure will be expressed as the total number of antibiotic days, defined as one antibiotic agent administered for one day. For example, if a patient receives two different antibiotics for five days, this equals 10 antibiotic days. The number of antibiotics used refers to the number of different antibiotic agents administered per day, not the number of individual doses or pills. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 4 Days of Antibiotics Group Participants will receive 4 days of antibiotic therapy administered as per the standard of care for the treatment of early ventilator associated pneumonia (VAP).
Standard of Care Antibiotic Therapy: Antibiotics will be administered as per the standard of care orally via tablet | 12 |
| 7 Days of Antibiotics Group Participants will receive 7 days of antibiotic therapy administered as per the standard of care for the treatment of early ventilator associated pneumonia (VAP).
Standard of Care Antibiotic Therapy: Antibiotics will be administered as per the standard of care orally via tablet | 15 |
| Total | 27 |
Baseline characteristics
| Characteristic | 4 Days of Antibiotics Group | 7 Days of Antibiotics Group | Total |
|---|---|---|---|
| Age, Continuous | 51 years | 43 years | 47 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 7 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 9 Participants |
| Number of Subjects with causative pathogen sensitive to initial empiric antibiotic | 12 Participants | 15 Participants | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 7 Participants | 11 Participants |
| Race (NIH/OMB) White | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 12 | 2 / 15 |
| other Total, other adverse events | 0 / 12 | 0 / 15 |
| serious Total, serious adverse events | 2 / 12 | 5 / 15 |
Outcome results
Primary
Antibiotic Free Days
The number of days where participant did not require the use of antibiotics
Time frame: Up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 Days of Antibiotics Group | Antibiotic Free Days | 17.2 Days | Standard Deviation 7.7 |
| 7 Days of Antibiotics Group | Antibiotic Free Days | 14 Days | Standard Deviation 6.6 |
Primary
Number of Participants With Reoccurring VAP
VAP recurrence will be reported as the number of participants with VAP occurring following completion of initial therapy.
Time frame: Up to 21 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 Days of Antibiotics Group | Number of Participants With Reoccurring VAP | 5 Participants |
| 7 Days of Antibiotics Group | Number of Participants With Reoccurring VAP | 7 Participants |
Secondary
Amount of Antibiotic Exposure
Antibiotic exposure will be expressed as the total number of antibiotic days, defined as one antibiotic agent administered for one day. For example, if a patient receives two different antibiotics for five days, this equals 10 antibiotic days. The number of antibiotics used refers to the number of different antibiotic agents administered per day, not the number of individual doses or pills.
Time frame: Up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 Days of Antibiotics Group | Amount of Antibiotic Exposure | 21.1 Antibiotic Days | Standard Deviation 13.4 |
| 7 Days of Antibiotics Group | Amount of Antibiotic Exposure | 23.8 Antibiotic Days | Standard Deviation 11 |
Secondary
Clinical Improvement as Measured by the Change in Clinical Pulmonary Infection Score (CPIS) From the First Study Day to the Last
Clinical improvement will be measured comparing the difference from the first study day to the last study day using daily Clinical Pulmonary Infection Score (CPIS) clinical score while enrolled in the study. CPIS has a total score ranging from 0 to 12 where a score of less than 6 indicates that the lung infection is considered controlled. A negative change may suggest improvement while a positive difference may suggest a worsening.
Time frame: From baseline to the last study day, up to 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 4 Days of Antibiotics Group | Clinical Improvement as Measured by the Change in Clinical Pulmonary Infection Score (CPIS) From the First Study Day to the Last | -2 Change of score on a scale |
| 7 Days of Antibiotics Group | Clinical Improvement as Measured by the Change in Clinical Pulmonary Infection Score (CPIS) From the First Study Day to the Last | -1 Change of score on a scale |
Secondary
Hospital Length Of Stay
Number of days participant was admitted in the hospital
Time frame: Up to 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 Days of Antibiotics Group | Hospital Length Of Stay | 66.9 Days | Standard Deviation 108.1 |
| 7 Days of Antibiotics Group | Hospital Length Of Stay | 33.7 Days | Standard Deviation 12.6 |
Secondary
ICU-free Days
The average number of days participants were not in the ICU
Time frame: Up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 Days of Antibiotics Group | ICU-free Days | 11.8 Days | Standard Deviation 9.7 |
| 7 Days of Antibiotics Group | ICU-free Days | 7.2 Days | Standard Deviation 6.4 |
Secondary
In-hospital Mortality
The number of participants that died while admitted in the hospital will be reported
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 Days of Antibiotics Group | In-hospital Mortality | 2 Participants |
| 7 Days of Antibiotics Group | In-hospital Mortality | 1 Participants |
Secondary
Number of Days of Antibiotic Exposure
The number of days when the participant received antibiotics
Time frame: Up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 Days of Antibiotics Group | Number of Days of Antibiotic Exposure | 12.8 Days | Standard Deviation 7.7 |
| 7 Days of Antibiotics Group | Number of Days of Antibiotic Exposure | 16 Days | Standard Deviation 6.6 |
Secondary
Number of Participants With VAP Relapse
VAP relapse will be reported as any recurrence of VAP caused by initial pathogen.
Time frame: Up to 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 Days of Antibiotics Group | Number of Participants With VAP Relapse | 1 Participants |
| 7 Days of Antibiotics Group | Number of Participants With VAP Relapse | 4 Participants |
Secondary
The Number of Participants That Received a Tracheostomy
The number of participants that received a tracheostomy
Time frame: Up to 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 Days of Antibiotics Group | The Number of Participants That Received a Tracheostomy | 2 Participants |
| 7 Days of Antibiotics Group | The Number of Participants That Received a Tracheostomy | 8 Participants |
Secondary
The Number of Participants With Empyema
The number of participants with empyema
Time frame: Up to 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 Days of Antibiotics Group | The Number of Participants With Empyema | 0 Participants |
| 7 Days of Antibiotics Group | The Number of Participants With Empyema | 0 Participants |
Secondary
The Number of Participants With Non-pulmonary Infections
The number of participants with Non-pulmonary infections
Time frame: Up to 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 Days of Antibiotics Group | The Number of Participants With Non-pulmonary Infections | 0 Participants |
| 7 Days of Antibiotics Group | The Number of Participants With Non-pulmonary Infections | 0 Participants |
Secondary
Ventilator-free Days
The average number of days participants did not use a ventilator
Time frame: Up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 Days of Antibiotics Group | Ventilator-free Days | 17.7 Days | Standard Deviation 5.3 |
| 7 Days of Antibiotics Group | Ventilator-free Days | 13.3 Days | Standard Deviation 11.1 |