Lower Respiratory Tract Infection (LRTI)
Conditions
Keywords
procalcitonin (PCT), lower respiratory tract infection (LRTI), antibiotic exposure, antibiotic decision making, community acquired pneumonia (CAP), chronic obstructive pulmonary disease (COPD) exacerbation, acute asthma exacerbation, acute bronchitis, procalcitonin guideline
Brief summary
The ProACT study is a 5 year, multicenter study that will test the effect of implementation of a novel procalcitonin guideline on antibiotic use and adverse outcomes in Emergency Department (ED) patients with Lower Respiratory Tract Infection (LRTI).
Detailed description
There is a need for improved decision-making for antibiotic prescription in acute suspected infection. Infections, particularly in the early stages, can have protean manifestations, often do not manifest with classic signs, and clinically overlap with non-infectious conditions. However, the imperative to quickly give antibiotics for bacterial infection has led to antibiotic overuse and resistance. Strategies that combine novel diagnostics with therapeutics have improved decision-making in oncology, cardiology, and other fields. These strategies aim to identify those patients most likely to be helped or harmed by the therapeutic intervention and allow more individualized care. This approach takes diagnostics to the next level, by demanding a test not only measure well, but also that clinical care be improved by tying the test to a treatment strategy. Procalcitonin, a novel biomarker of bacterial infection, may help physicians make more appropriate antibiotic decisions. Lower respiratory tract infection (LRTI) is an ideal trial population. LRTI accounts for a large proportion of antibiotic prescription, and exemplifies the imprecise clinical phenotype of infection.However, key questions of generalizability and safety preclude widespread application.
Interventions
OTHERProcalcitonin level
A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion.
OTHERResults of procalcitonin (PCT) level to treating clinician
In the ED, we will quickly (\<1 hour goal) provide clinicians the procalcitonin result.
OTHERProvide procalcitonin guideline to treating clinician
Procalcitonin antibiotic guideline -- Procalcitonin level (ug/L) -- Bacterial etiology -- Recommendation \< 0.1 -- Very unlikely -- Antibiotics strongly discouraged(1) 0.1 - 0.25 -- Unlikely -- Antibiotics discouraged(1) \> 0.25 - 0.5 -- Likely -- Antibiotics recommended(2) \> 0.5 -- Very likely -- Antibiotics strongly recommended(2) 1. Initial antibiotics can be considered for critical illness, Legionella pneumophilia. Procalcitonin should be evaluated in context with all findings and the total clinical status; clinical judgment always necessary. 2. For outpatients, antibiotic duration based on level (\> 0.25-0.5 ug/L:3 days; \> 0.5-1.0 ug/L:5 days; \>1.0 ug/L:7 days). Physician follow-up is recommended.
OTHERTelephone Visit
We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30
Sponsors
National Institute of General Medical Sciences (NIGMS)
BioMérieux
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years old * A primary clinical diagnosis in the ED of acute LRTI (\< 28 days duration) * Clinician willing to consider procalcitonin in antibiotic decision-making
Exclusion criteria
* Systemic antibiotics before ED presentation (All prophylactic antibiotic regimens, OR received \>1 dose within 72 hours prior to ED presentation) * Current vasopressor use * Mechanical ventilation (via endotracheal tube) * Known severe immunosuppression * Accompanying non-respiratory infections * Known lung abscess or empyema * Chronic dialysis * Metastatic cancer * Surgery in the past 7 days (excluding minor surgery such as skin biopsy) * Incarcerated or homeless * Enrolled in ProACT in the past 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Antibiotic Exposure Days | 30 days | Total antibiotic exposure, defined as the total number of antibiotic-days by Day 30. |
| Number of Participants With Any Adverse Outcome | 30 days | Primary Safety Outcome - Combined endpoint of adverse outcomes (death, endotracheal intubation, vasopressors, renal failure, lung abscess/empyema, pneumonia in non-CAP patient, and hospital readmissions) that could be attributable to withholding antibiotics in lower respiratory tract infection (LRTI). Number is based on the number of participants that experienced any adverse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibiotic Prescription in Emergency Department(ED) | While in the ED or before ED discharge (majority patients < 1 day) | Antibiotic prescription in the ED includes post-randomization receipt of antibiotics in ED and provision of an antibiotic prescription for patients at the time of discharge from the ED. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled in the Emergency Department (ED) if they had a primary clinical diagnosis of acute Lower Respiratory Tract Infection \[LRTI\] (\< 28 days duration) and their key clinician was willing to consider Procalcitonin (PCT) result in Antibiotic (ABX) decision making.
Pre-assignment details
Only 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate.
Participants by arm
| Arm | Count |
|---|---|
| Procalcitonin (PCT) Group Procalcitonin level: A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion.
Results of procalcitonin (PCT) level to treating clinician: In the ED, we will quickly (\<1 hour goal) provide clinicians the procalcitonin result.
Provide PCT guideline to treating clinician: Procalcitonin antibiotic guideline --
PCT level (ug/L)-- Bacterial etiology -- Recommendation \< 0.1-- Very unlikely -- Antibiotics strongly discouraged 0.1 - 0.25 -- Unlikely--Antibiotics discouraged \> 0.25 - 0.5--Likely -- Antibiotics recommended \> 0.5-- Very likely -- Antibiotics strongly recommended
Telephone Visit: We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30 | 826 |
| Usual Care (UC) Group Telephone Visit at Day 15 and Day 30
Telephone Visit: We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30 | 830 |
| Total | 1,656 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 151 | 160 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Procalcitonin (PCT) Group | Usual Care (UC) Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 7 Participants | 12 Participants |
| Age, Categorical >=65 years | 218 Participants | 227 Participants | 445 Participants |
| Age, Categorical Between 18 and 65 years | 603 Participants | 596 Participants | 1199 Participants |
| Age, Continuous | 52.9 years STANDARD_DEVIATION 18.4 | 53.2 years STANDARD_DEVIATION 18.7 | 53.1 years STANDARD_DEVIATION 18.5 |
| Race/Ethnicity, Customized Black | 296 Participants | 297 Participants | 593 Participants |
| Race/Ethnicity, Customized Hispanic | 108 Participants | 104 Participants | 212 Participants |
| Race/Ethnicity, Customized White | 455 Participants | 470 Participants | 925 Participants |
| Region of Enrollment United States | 826 participants | 830 participants | 1656 participants |
| Sex: Female, Male Female | 469 Participants | 476 Participants | 945 Participants |
| Sex: Female, Male Male | 357 Participants | 354 Participants | 711 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 826 | 10 / 830 |
| other Total, other adverse events | 20 / 826 | 14 / 830 |
| serious Total, serious adverse events | 14 / 826 | 9 / 830 |
Outcome results
Primary
Number of Participants With Any Adverse Outcome
Primary Safety Outcome - Combined endpoint of adverse outcomes (death, endotracheal intubation, vasopressors, renal failure, lung abscess/empyema, pneumonia in non-CAP patient, and hospital readmissions) that could be attributable to withholding antibiotics in lower respiratory tract infection (LRTI). Number is based on the number of participants that experienced any adverse outcome.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Procalcitonin (PCT) Group | Number of Participants With Any Adverse Outcome | 96 Participants |
| Usual Care Group | Number of Participants With Any Adverse Outcome | 109 Participants |
p-value: <0.001Chi-squared
Primary
Total Antibiotic Exposure Days
Total antibiotic exposure, defined as the total number of antibiotic-days by Day 30.
Time frame: 30 days
Population: Mixed modeling was used to impute missing data for the intention-to-treat analysis for the primary outcome since not all patients could be reached for the 30 day interview (which collected 30 day antibiotic use).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Procalcitonin (PCT) Group | Total Antibiotic Exposure Days | 4.2 days | Standard Deviation 5.8 |
| Usual Care Group | Total Antibiotic Exposure Days | 4.3 days | Standard Deviation 5.6 |
p-value: 0.87t-test, 2 sided
Secondary
Antibiotic Prescription in Emergency Department(ED)
Antibiotic prescription in the ED includes post-randomization receipt of antibiotics in ED and provision of an antibiotic prescription for patients at the time of discharge from the ED.
Time frame: While in the ED or before ED discharge (majority patients < 1 day)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Procalcitonin (PCT) Group | Antibiotic Prescription in Emergency Department(ED) | 282 Participants |
| Usual Care Group | Antibiotic Prescription in Emergency Department(ED) | 321 Participants |
95% CI: [-12.2, 30]