Pneumonia, Bacterial
Conditions
Brief summary
Trials comparing PCT-guided antibiotic algorithms to standard management show a significant reduction in antibiotic exposure without an increase in mortality or treatment failure. Despite this strong evidence from multiple studies a recent prospective multicentric interventional trial in the US fell short of demonstrating antibiotic reductions by PCT-guided antibiotic management. Amongst other limitations the authors of that study concluded that successful implementation of PCT may require closer educational oversight. As such, this study will compare effectiveness and safety of antibiotic prescription guided by a PCT-algorithm via a Stewardship Team over standard guidelines in hospitalized adult patients with suspected or confirmed LRTI (including sepsis with respiratory focus).
Interventions
DIAGNOSTIC_TESTprocalcitonin
accuracy of procalcitonin as a diagnostic marker in guiding antibiotic therapy in patients with a lower respiratory tract infection
Sponsors
BRAHMS GmbH
Thermo Fisher Scientific, Inc
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
Inclusion criteria
* Hospitalized adult patients ≥ 18 years of age * Suspected or confirmed pneumonia \<28 days at time of admission to the hospital (ED) who are prescribed antibiotics * Minimum of 2 (two) blood samples available for PCT value assessment within 24 hours of hospitalization
Exclusion criteria
* Patient has tested positive for SARS-CoV-2 * Non-hospitalized patients * Patients admitted to home health * Major surgeries, defined as any procedure in which an incision is made with the exception of superficial procedures (eyes, cornea, skin, dental procedures), organs removed, or normal anatomy altered (e.g. open thoracic, abdominal and/or major orthopedic surgery), in the past 1 month or expected surgical procedure or patient receiving antibiotics for surgical prophylaxis * Active metastatic cancer or neuroendocrine tumor or liquid tumor and/or on check point inhibitors within 3 months or has signs of mucositis (e.g. mouth lesions or intestinal bleeding) * Known pregnancy * Primary and acquired cell-mediated immune deficiency (HIV with CD4 \<350 cells/mm³; receipt of systemic chemotherapy and/or biologics in the past 3 months for reasons other than malignancy) * Infection where long course antibiotics are the standard of care(\>2 weeks) other than anti-inflammatory reasons. * Neutropenia (\<1,500 ANC) * Concomitant non-pulmonary bacterial infection that requires antibiotic therapy based on an active medical team decision * Antibiotics given for non-infectious indications (e.g. rifaximin for hepatic encephalopathy) * Patients with cystic fibrosis * Patients receiving dialysis * Patients with solid organ transplant, bone marrow transplant or stem cell transplant recipient * ST elevation myocardial infarction * Prior enrollment into this study within 30 days * Patient experiencing major trauma defined as any injury that could cause prolonged disability and/or an Injury Severity Score \>15, and/or burns or patient under extracorporeal circulation confirmed by a second research staff member. * Patient with acute viral hepatitis and/or decompensated severe liver cirrhosis (Child-Pugh Class C). * Patient with prolonged or severe cardiogenic shock, defined as decreased cardiac output leading to end organ injury (e.g. severe hypotension or AKI or oliguria or altered mental status or cool extremities or respiratory distress AND evidence of metabolic acidosis on lab testing) * Patient with pancreatitis, chemical pneumonitis or heat stroke * Active infection with invasive fungal pathogen (e.g. candidiasis, aspergillosis) or plasmodium falciparum malaria or mycobacteria * Patient under treatment with OKT3 antibodies, OK-432, interleukins, TNF-alpha and other drugs stimulating the release of pro-inflammatory cytokines or resulting in anaphylaxis. * Patient is under hospice care * Patient with ventilator associated pneumonia * Patients with untreated, active, and symptomatic autoimmune disease * Patients with empyema, abscess, or cavitary/necrotizing pneumonia * Patients actively enrolled in other clinical trial involving immunomodulatory therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short Treatment of Pneumonia | 30 days | Proportion of patients with short treatment of pneumonia with antibiotics (less than 4 days, shortABx) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite Safety Adverse Event Rate | 30 days | Composite endpoints include: all-cause in-hospital mortality, all-cause mortality after discharge (as available), hospital readmission, septic shock (vasopressor use for \> 1 hour), mechanical ventilation (via endotracheal tube), required dialysis, lung abscess/empyema/cavitation/necrotizing pneumonia |
| Antibiotic Exposure at Discharge | 30 days | Duration of antibiotics prescribed at discharge |
| Days of Therapy Per 1000 Patient Days | 30 days | Days of therapy per 1000 patient days (inclusive of antibiotics prescribed at discharge) |
| Length of Stay | 30 days | Length of stay in hospital |
| ICU Admissions | 30 days | Number of Participants Admitted to the ICU |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clostridium Difficile Infection (CDI) | 30 days | Treatment or readmission for CDI until day 30 after enrollment |
| Healthcare Economic Endpoints | 30 days | Costs associated with primary hospitalization, readmission for CDI, and loss of function |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care (SOC) PCT results were hidden from the medical record and no ASP recommendation given. | 357 |
| PCT/ASP PCT results were posted in the medical record and ASP emailed recommendation to the medical team. | 343 |
| Total | 700 |
Baseline characteristics
| Characteristic | Total | PCT/ASP | Standard of Care (SOC) |
|---|---|---|---|
| Age, Continuous | 72 years | 71 years | 73 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 72 Participants | 29 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 608 Participants | 303 Participants | 305 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 20 Participants | 11 Participants | 9 Participants |
| Pneumonia Severity Index (PSI) Class II | 89 Participants | 44 Participants | 45 Participants |
| Pneumonia Severity Index (PSI) Class III | 142 Participants | 64 Participants | 78 Participants |
| Pneumonia Severity Index (PSI) Class I (lowest severity) | 30 Participants | 16 Participants | 14 Participants |
| Pneumonia Severity Index (PSI) Class IV | 300 Participants | 156 Participants | 144 Participants |
| Pneumonia Severity Index (PSI) Class V (highest severity) | 139 Participants | 63 Participants | 76 Participants |
| Pneumonia Type Aspiration | 171 Participants | 82 Participants | 89 Participants |
| Pneumonia Type CAP (community-acquired pneumonia) | 401 Participants | 196 Participants | 205 Participants |
| Pneumonia Type HCAP (healthcare-associated pneumonia) | 25 Participants | 15 Participants | 10 Participants |
| Pneumonia Type Other | 103 Participants | 50 Participants | 53 Participants |
| Sex: Female, Male Female | 330 Participants | 164 Participants | 166 Participants |
| Sex: Female, Male Male | 370 Participants | 179 Participants | 191 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 357 | 17 / 343 |
| other Total, other adverse events | 0 / 357 | 0 / 343 |
| serious Total, serious adverse events | 76 / 357 | 81 / 343 |
Outcome results
Primary
Short Treatment of Pneumonia
Proportion of patients with short treatment of pneumonia with antibiotics (less than 4 days, shortABx)
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care (SOC) | Short Treatment of Pneumonia | 47 Participants |
| PCT/ASP | Short Treatment of Pneumonia | 87 Participants |
Secondary
Antibiotic Exposure at Discharge
Duration of antibiotics prescribed at discharge
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (SOC) | Antibiotic Exposure at Discharge | 0 days |
| PCT/ASP | Antibiotic Exposure at Discharge | 0 days |
Secondary
Composite Safety Adverse Event Rate
Composite endpoints include: all-cause in-hospital mortality, all-cause mortality after discharge (as available), hospital readmission, septic shock (vasopressor use for \> 1 hour), mechanical ventilation (via endotracheal tube), required dialysis, lung abscess/empyema/cavitation/necrotizing pneumonia
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care (SOC) | Composite Safety Adverse Event Rate | 72 Participants |
| PCT/ASP | Composite Safety Adverse Event Rate | 90 Participants |
Secondary
Days of Therapy Per 1000 Patient Days
Days of therapy per 1000 patient days (inclusive of antibiotics prescribed at discharge)
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (SOC) | Days of Therapy Per 1000 Patient Days | 1.25 Days of Therapy Per 1000 Patient Days |
| PCT/ASP | Days of Therapy Per 1000 Patient Days | 1.14 Days of Therapy Per 1000 Patient Days |
Secondary
ICU Admissions
Number of Participants Admitted to the ICU
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care (SOC) | ICU Admissions | 43 Participants |
| PCT/ASP | ICU Admissions | 49 Participants |
Secondary
Length of Stay
Length of stay in hospital
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (SOC) | Length of Stay | 4 days |
| PCT/ASP | Length of Stay | 4 days |
Other Pre-specified
Clostridium Difficile Infection (CDI)
Treatment or readmission for CDI until day 30 after enrollment
Time frame: 30 days
Other Pre-specified
Healthcare Economic Endpoints
Costs associated with primary hospitalization, readmission for CDI, and loss of function
Time frame: 30 days