Pneumonia
Conditions
Keywords
PNA, CPOE, Empiric Therapy
Brief summary
The INSPIRE-ASP PNA trial is a cluster-randomized controlled trial of HCA hospitals comparing routine empiric antibiotic stewardship practices with real-time precision medicine computerized physician order entry smart prompts providing the probability that a non-critically ill adult admitted with PNA is infected with a resistant pathogen. Note: that enrolled subjects represents 59 individual HCA hospitals that have been randomized.
Interventions
Quality improvement intervention: computerized physician order entry (CPOE) decision support alert that provides physicians with patient-specific risk estimate of having PNA due to a multidrug resistant organism (MDRO) and recommends appropriate antibiotic choice for non-ICU patients in the first 3 days of hospitalization. Continuation of other antibiotic stewardship activities in accordance with national standards.
OTHERRoutine Care
Routine Antibiotic Stewardship Arm - Continuation of all antibiotic stewardship activities in accordance with national standards.
Sponsors
Hospital Corporation of America
University of California, Irvine
University of Massachusetts, Amherst
Brigham and Women's Hospital
Centers for Disease Control and Prevention
Harvard Pilgrim Health Care
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
This cluster-randomized trial will assess a novel quality improvement antibiotic stewardship strategy for empiric antibiotic selection.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Facility Inclusion Criteria: * HCA hospitals admitting adults with PNA * Facility use of MEDITECH as their electronic health record system Facility
Exclusion criteria
\- Note: unit of randomization is the hospital, however the CPOE alert intervention will calculate risk estimates for adults age \>=18 admitted to non-ICU wards and who are ordered to receive extended-spectrum antibiotics for PNA. Prisoners were excluded from prompts and analysis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extended-Spectrum Days Of Antibacterial Therapy (ES-DOT) Per Empiric Day | First 3 days of hospitalization for each patient during 15-month intervention period | The number of different extended-spectrum antibacterials received by the patient each empiric day-of-therapy (outcome measure unit), averaged over the empiric days (the first 3 days of hospitalization), summed across all participants. Note that Days-of-Therapy unit is a standardized national measure for antibacterial use in hospitals. For clarity the calculation is as follows: we define a DOT for a particular ES antibiotic as a day in which any number of doses of that antibiotic is given. Different ES antibiotics are summed across the empiric days for each patient admission, then divided by the empiric days for that patient-admission to determine each admission's DOT per at-risk day. If an admission is less than 3 days, only the number of days the patient is admitted will contribute to the numerator and denominator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vancomycin Days of Antibacterial Therapy Per Empiric Day | First 3 days of hospitalization for each patient during 15-month intervention period | The number of days that Vancomycin is received by the patient averaged over the empiric days (the first 3 days of hospitalization), summed across all participants. Note that Days-of-Therapy unit is a standardized national measure for antibacterial use in hospitals. For clarity the calculation is as follows: we define a DOT for a particular ES antibiotic as a day in which any number of doses of that antibiotic is given. Different ES antibiotics are summed across the empiric days for each patient admission, then divided by the empiric days for that patient-admission to determine each admission's DOT per at-risk day. If an admission is less than 3 days, only the number of days the patient is admitted will contribute to the numerator and denominator. |
| Antipseudomonal Antibiotic Days Of Therapy (ES-DOT) Per Empiric Day | First 3 days of hospitalization for each patient during 15-month intervention period | The number of different antipseudomonals received by the patient each empiric day of therapy, averaged over the empiric days (the first 3 days of hospitalization), summed across all participants. Note that Days-of-Therapy unit is a standardized national measure for antibacterial use in hospitals. For clarity the calculation is as follows: we define a DOT for a particular ES antibiotic as a day in which any number of doses of that antibiotic is given. Different ES antibiotics are summed across the empiric days for each patient admission, then divided by the empiric days for that patient-admission to determine each admission's DOT per at-risk day. If an admission is less than 3 days, only the number of days the patient is admitted will contribute to the numerator and denominator. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Extended-Spectrum Days of Therapy With Inpatient Extended-Spectrum (ES) Antibacterial Treatment After Empiric Period | 15 month intervention | The summed number of different ES antibacterials received each day, measured repeatedly on or after 4 calendar days of admission and divided by the number of days from hospital day 4 through discharge. Note: this outcome is intended for a secondary manuscript. |
| Empiric and Total Antibacterial Costs | 15 month intervention | Empiric and total antibacterial costs during hospitalization. Note: this outcome is intended for a secondary manuscript. |
| Antibacterial Escalations [Safety Outcome 1] | Duration of hospitalization for each patient during 15-month intervention period | Days from start of standard-spectrum antibacterial until switch to extended-spectrum antibacterial during hospital stay, if that occurs. If it doesn't occur, the number of days is censored (capped) at the patient's hospital discharge or at the end of data collection. Almost all patients will be discharged before the end of trial data collection. |
| Incidence of Hospital-Onset MDRO-Positive Cultures | 15 month intervention | Newly-detected hospital-onset MDRO-positive cultures (on or after 3 calendar days of admission). Includes total MDRO and specific MDRO subsets. Note: this outcome is intended for a secondary manuscript. |
| Fluoroquinolone (FQ) Days of Therapy Per Empiric and Total At-risk Days | 15 month intervention | The summed number of different fluoroquinolone antibacterials received each day, measured repeatedly over (1) the first three days (empiric) of an admission and divided by the number of days of the admission and (2) all days of an admission divided by the total number of admission days. Note: this outcome is intended for a secondary manuscript. |
| Incidence of Hospital-Onset C. Difficile | 15 month intervention | Hospital-onset C. difficile positive tests (specimen obtained) after 3 calendar days of admission during hospitalization. Note: this outcome is intended for a secondary manuscript. |
| ICU Transfers [Safety Outcome 2] | Duration of hospitalization for each patient during 15-month intervention period | Days from hospital admission until transfer to ICU, if that occurs. If it doesn't occur, the number of days is censored (capped) at the patient's hospital discharge or at the end of data collection. Almost all patients will be discharged before the end of trial data collection. |
| Length-of-stay [Safety Outcome 3] | Duration of hospitalization for each patient during 15-month intervention period | Days from hospital admission until discharge. If the patient remains in the hospital at the end of the trial data collection, the number of days is censored (capped) at that time. Almost all patients will be discharged before the end of trial data collection. |
Countries
United States
Participant flow
Recruitment details
59 out of 143 HCA Healthcare hospitals were recruited for this trial. There was a 15 month intervention period from April 1, 2019 through June 30, 2020.
Pre-assignment details
44,780 patients were involved in the intervention period from the 59 participating hospitals.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Routine Stewardship Continuation of all antibiotic stewardship activities in accordance with national standards. | 21,998 |
| Arm 2: CPOE Bundle Use of a computerized physician order entry (CPOE) smart prompt alert to guide empiric choice of antibiotics for PNA in non-ICU patients in the first 3 days of hospitalization.
INSPIRE CPOE Smart Prompt: Quality improvement intervention: computerized physician order entry (CPOE) decision support alert that provides physicians with patient-specific risk estimate of having PNA due to a multidrug resistant organism (MDRO) and recommends appropriate antibiotic choice for non-ICU patients in the first 3 days of hospitalization.
Continuation of other antibiotic stewardship activities in accordance with national standards. | 22,782 |
| Total | 44,780 |
Baseline characteristics
| Characteristic | Arm 1: Routine Stewardship | Arm 2: CPOE Bundle | Total |
|---|---|---|---|
| Age, Continuous | 67.4 years STANDARD_DEVIATION 17.3 | 68.0 years STANDARD_DEVIATION 17 | 68.0 years STANDARD_DEVIATION 17 |
| Race/Ethnicity, Customized Race Black | 2848 Participants | 2908 Participants | 5756 Participants |
| Race/Ethnicity, Customized Race Other | 898 Participants | 1304 Participants | 2202 Participants |
| Race/Ethnicity, Customized Race White | 15415 Participants | 17205 Participants | 32620 Participants |
| Sex: Female, Male Female | 11400 Participants | 11768 Participants | 23168 Participants |
| Sex: Female, Male Male | 10545 Participants | 10966 Participants | 21511 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21,998 | 0 / 22,782 |
| other Total, other adverse events | 0 / 21,998 | 0 / 22,782 |
| serious Total, serious adverse events | 0 / 21,998 | 0 / 22,782 |
Outcome results
Primary
Extended-Spectrum Days Of Antibacterial Therapy (ES-DOT) Per Empiric Day
The number of different extended-spectrum antibacterials received by the patient each empiric day-of-therapy (outcome measure unit), averaged over the empiric days (the first 3 days of hospitalization), summed across all participants. Note that Days-of-Therapy unit is a standardized national measure for antibacterial use in hospitals. For clarity the calculation is as follows: we define a DOT for a particular ES antibiotic as a day in which any number of doses of that antibiotic is given. Different ES antibiotics are summed across the empiric days for each patient admission, then divided by the empiric days for that patient-admission to determine each admission's DOT per at-risk day. If an admission is less than 3 days, only the number of days the patient is admitted will contribute to the numerator and denominator.
Time frame: First 3 days of hospitalization for each patient during 15-month intervention period
Population: The total number of participants analyzed reported here is from the intervention period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Routine Stewardship | Extended-Spectrum Days Of Antibacterial Therapy (ES-DOT) Per Empiric Day | 38690 Extended-Spectrum Days-of-Therapy |
| Arm 2: CPOE Bundle | Extended-Spectrum Days Of Antibacterial Therapy (ES-DOT) Per Empiric Day | 27971 Extended-Spectrum Days-of-Therapy |
Secondary
Antipseudomonal Antibiotic Days Of Therapy (ES-DOT) Per Empiric Day
The number of different antipseudomonals received by the patient each empiric day of therapy, averaged over the empiric days (the first 3 days of hospitalization), summed across all participants. Note that Days-of-Therapy unit is a standardized national measure for antibacterial use in hospitals. For clarity the calculation is as follows: we define a DOT for a particular ES antibiotic as a day in which any number of doses of that antibiotic is given. Different ES antibiotics are summed across the empiric days for each patient admission, then divided by the empiric days for that patient-admission to determine each admission's DOT per at-risk day. If an admission is less than 3 days, only the number of days the patient is admitted will contribute to the numerator and denominator.
Time frame: First 3 days of hospitalization for each patient during 15-month intervention period
Population: The total number of participants analyzed reported here is from the intervention period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Routine Stewardship | Antipseudomonal Antibiotic Days Of Therapy (ES-DOT) Per Empiric Day | 22683 Antipseudomonal Days-of-Therapy |
| Arm 2: CPOE Bundle | Antipseudomonal Antibiotic Days Of Therapy (ES-DOT) Per Empiric Day | 15670 Antipseudomonal Days-of-Therapy |
Secondary
Vancomycin Days of Antibacterial Therapy Per Empiric Day
The number of days that Vancomycin is received by the patient averaged over the empiric days (the first 3 days of hospitalization), summed across all participants. Note that Days-of-Therapy unit is a standardized national measure for antibacterial use in hospitals. For clarity the calculation is as follows: we define a DOT for a particular ES antibiotic as a day in which any number of doses of that antibiotic is given. Different ES antibiotics are summed across the empiric days for each patient admission, then divided by the empiric days for that patient-admission to determine each admission's DOT per at-risk day. If an admission is less than 3 days, only the number of days the patient is admitted will contribute to the numerator and denominator.
Time frame: First 3 days of hospitalization for each patient during 15-month intervention period
Population: The total number of participants analyzed reported here is from the intervention period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Routine Stewardship | Vancomycin Days of Antibacterial Therapy Per Empiric Day | 13778 Vancomycin Days-of-Therapy |
| Arm 2: CPOE Bundle | Vancomycin Days of Antibacterial Therapy Per Empiric Day | 10534 Vancomycin Days-of-Therapy |
Other Pre-specified
Antibacterial Escalations [Safety Outcome 1]
Days from start of standard-spectrum antibacterial until switch to extended-spectrum antibacterial during hospital stay, if that occurs. If it doesn't occur, the number of days is censored (capped) at the patient's hospital discharge or at the end of data collection. Almost all patients will be discharged before the end of trial data collection.
Time frame: Duration of hospitalization for each patient during 15-month intervention period
Population: The mean number of days to event here is from the intervention period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Routine Stewardship | Antibacterial Escalations [Safety Outcome 1] | 5.3 Days to event | Standard Deviation 3.8 |
| Arm 2: CPOE Bundle | Antibacterial Escalations [Safety Outcome 1] | 6.1 Days to event | Standard Deviation 5.9 |
Other Pre-specified
Empiric and Total Antibacterial Costs
Empiric and total antibacterial costs during hospitalization. Note: this outcome is intended for a secondary manuscript.
Time frame: 15 month intervention
Other Pre-specified
Extended-Spectrum Days of Therapy With Inpatient Extended-Spectrum (ES) Antibacterial Treatment After Empiric Period
The summed number of different ES antibacterials received each day, measured repeatedly on or after 4 calendar days of admission and divided by the number of days from hospital day 4 through discharge. Note: this outcome is intended for a secondary manuscript.
Time frame: 15 month intervention
Other Pre-specified
Fluoroquinolone (FQ) Days of Therapy Per Empiric and Total At-risk Days
The summed number of different fluoroquinolone antibacterials received each day, measured repeatedly over (1) the first three days (empiric) of an admission and divided by the number of days of the admission and (2) all days of an admission divided by the total number of admission days. Note: this outcome is intended for a secondary manuscript.
Time frame: 15 month intervention
Other Pre-specified
ICU Transfers [Safety Outcome 2]
Days from hospital admission until transfer to ICU, if that occurs. If it doesn't occur, the number of days is censored (capped) at the patient's hospital discharge or at the end of data collection. Almost all patients will be discharged before the end of trial data collection.
Time frame: Duration of hospitalization for each patient during 15-month intervention period
Population: The mean number of days to event here is from the intervention period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Routine Stewardship | ICU Transfers [Safety Outcome 2] | 6.5 Days to event | Standard Deviation 5.2 |
| Arm 2: CPOE Bundle | ICU Transfers [Safety Outcome 2] | 7.1 Days to event | Standard Deviation 5.9 |
Other Pre-specified
Incidence of Hospital-Onset C. Difficile
Hospital-onset C. difficile positive tests (specimen obtained) after 3 calendar days of admission during hospitalization. Note: this outcome is intended for a secondary manuscript.
Time frame: 15 month intervention
Other Pre-specified
Incidence of Hospital-Onset MDRO-Positive Cultures
Newly-detected hospital-onset MDRO-positive cultures (on or after 3 calendar days of admission). Includes total MDRO and specific MDRO subsets. Note: this outcome is intended for a secondary manuscript.
Time frame: 15 month intervention
Other Pre-specified
Length-of-stay [Safety Outcome 3]
Days from hospital admission until discharge. If the patient remains in the hospital at the end of the trial data collection, the number of days is censored (capped) at that time. Almost all patients will be discharged before the end of trial data collection.
Time frame: Duration of hospitalization for each patient during 15-month intervention period
Population: The mean number of days to event here is from the intervention period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Routine Stewardship | Length-of-stay [Safety Outcome 3] | 6.8 Days to event | Standard Deviation 5.9 |
| Arm 2: CPOE Bundle | Length-of-stay [Safety Outcome 3] | 7.1 Days to event | Standard Deviation 6.9 |